CN107167529A - The assay method of the Reinheitszahl and uncertainty of phenol and hydroquinones standard substance - Google Patents
The assay method of the Reinheitszahl and uncertainty of phenol and hydroquinones standard substance Download PDFInfo
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- CN107167529A CN107167529A CN201710305125.9A CN201710305125A CN107167529A CN 107167529 A CN107167529 A CN 107167529A CN 201710305125 A CN201710305125 A CN 201710305125A CN 107167529 A CN107167529 A CN 107167529A
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- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 title claims abstract description 82
- 238000003556 assay Methods 0.000 title claims abstract description 25
- 239000000126 substance Substances 0.000 title claims abstract description 18
- 150000005208 1,4-dihydroxybenzenes Chemical class 0.000 title claims abstract 18
- 238000000034 method Methods 0.000 claims abstract description 158
- 238000012360 testing method Methods 0.000 claims abstract description 126
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 93
- 238000004817 gas chromatography Methods 0.000 claims abstract description 50
- 239000002994 raw material Substances 0.000 claims abstract description 25
- 238000013094 purity test Methods 0.000 claims abstract description 18
- 238000012790 confirmation Methods 0.000 claims abstract description 17
- 238000011156 evaluation Methods 0.000 claims abstract description 17
- 238000013112 stability test Methods 0.000 claims abstract description 14
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 claims abstract description 10
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 4
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 4
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 42
- 239000012535 impurity Substances 0.000 claims description 32
- 238000012856 packing Methods 0.000 claims description 32
- 238000010792 warming Methods 0.000 claims description 31
- 238000000113 differential scanning calorimetry Methods 0.000 claims description 24
- 238000007689 inspection Methods 0.000 claims description 16
- 238000001514 detection method Methods 0.000 claims description 13
- 239000013557 residual solvent Substances 0.000 claims description 13
- 239000007789 gas Substances 0.000 claims description 12
- 230000003068 static effect Effects 0.000 claims description 12
- 238000004458 analytical method Methods 0.000 claims description 11
- 238000010606 normalization Methods 0.000 claims description 11
- 238000004364 calculation method Methods 0.000 claims description 10
- 241001269238 Data Species 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 9
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 8
- 239000007787 solid Substances 0.000 claims description 8
- 239000012159 carrier gas Substances 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 7
- 238000005070 sampling Methods 0.000 claims description 7
- 238000009826 distribution Methods 0.000 claims description 6
- 238000005259 measurement Methods 0.000 claims description 6
- 238000012544 monitoring process Methods 0.000 claims description 6
- 238000012545 processing Methods 0.000 claims description 6
- 238000010438 heat treatment Methods 0.000 claims description 5
- 238000001543 one-way ANOVA Methods 0.000 claims description 5
- 235000010210 aluminium Nutrition 0.000 claims description 4
- PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 claims description 4
- 229910052593 corundum Inorganic materials 0.000 claims description 4
- 238000005868 electrolysis reaction Methods 0.000 claims description 4
- 238000010812 external standard method Methods 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 238000002844 melting Methods 0.000 claims description 4
- 230000008018 melting Effects 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- 238000003359 percent control normalization Methods 0.000 claims description 4
- RGCLLPNLLBQHPF-HJWRWDBZSA-N phosphamidon Chemical compound CCN(CC)C(=O)C(\Cl)=C(/C)OP(=O)(OC)OC RGCLLPNLLBQHPF-HJWRWDBZSA-N 0.000 claims description 4
- 230000010287 polarization Effects 0.000 claims description 4
- 238000003825 pressing Methods 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- 238000005979 thermal decomposition reaction Methods 0.000 claims description 4
- 229910001845 yogo sapphire Inorganic materials 0.000 claims description 4
- 239000002131 composite material Substances 0.000 claims description 3
- 238000000205 computational method Methods 0.000 claims description 3
- 238000007619 statistical method Methods 0.000 claims description 3
- 238000007707 calorimetry Methods 0.000 claims description 2
- 238000005303 weighing Methods 0.000 claims description 2
- 239000000243 solution Substances 0.000 claims 5
- 238000002347 injection Methods 0.000 claims 1
- 239000007924 injection Substances 0.000 claims 1
- 238000004153 renaturation Methods 0.000 claims 1
- 239000000463 material Substances 0.000 abstract description 13
- 238000003672 processing method Methods 0.000 abstract description 2
- 230000009897 systematic effect Effects 0.000 abstract description 2
- 125000000687 hydroquinonyl group Chemical class C1(O)=C(C=C(O)C=C1)* 0.000 description 52
- 239000002537 cosmetic Substances 0.000 description 14
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 239000000654 additive Substances 0.000 description 6
- 238000005457 optimization Methods 0.000 description 6
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 6
- 230000000996 additive effect Effects 0.000 description 5
- 230000005540 biological transmission Effects 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 230000009286 beneficial effect Effects 0.000 description 4
- 238000001938 differential scanning calorimetry curve Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- NAWXUBYGYWOOIX-SFHVURJKSA-N (2s)-2-[[4-[2-(2,4-diaminoquinazolin-6-yl)ethyl]benzoyl]amino]-4-methylidenepentanedioic acid Chemical compound C1=CC2=NC(N)=NC(N)=C2C=C1CCC1=CC=C(C(=O)N[C@@H](CC(=C)C(O)=O)C(O)=O)C=C1 NAWXUBYGYWOOIX-SFHVURJKSA-N 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 238000011067 equilibration Methods 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000000227 grinding Methods 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- 238000005057 refrigeration Methods 0.000 description 3
- 238000012216 screening Methods 0.000 description 3
- 241000894007 species Species 0.000 description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- 230000002146 bilateral effect Effects 0.000 description 2
- 150000001793 charged compounds Chemical class 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
- 238000003908 quality control method Methods 0.000 description 2
- 239000012925 reference material Substances 0.000 description 2
- 238000000611 regression analysis Methods 0.000 description 2
- 230000001568 sexual effect Effects 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 238000002411 thermogravimetry Methods 0.000 description 2
- 208000003351 Melanosis Diseases 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000012937 correction Methods 0.000 description 1
- 229910052571 earthenware Inorganic materials 0.000 description 1
- 238000009415 formwork Methods 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000001819 mass spectrum Methods 0.000 description 1
- 150000002989 phenols Chemical class 0.000 description 1
- 239000002453 shampoo Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3577—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing liquids, e.g. polluted water
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N27/00—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means
- G01N27/26—Investigating or analysing materials by the use of electric, electrochemical, or magnetic means by investigating electrochemical variables; by using electrolysis or electrophoresis
- G01N27/416—Systems
- G01N27/42—Measuring deposition or liberation of materials from an electrolyte; Coulometry, i.e. measuring coulomb-equivalent of material in an electrolyte
- G01N27/423—Coulometry
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N5/00—Analysing materials by weighing, e.g. weighing small particles separated from a gas or liquid
- G01N5/04—Analysing materials by weighing, e.g. weighing small particles separated from a gas or liquid by removing a component, e.g. by evaporation, and weighing the remainder
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N2021/3595—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light using FTIR
Abstract
The invention discloses the assay method of the Reinheitszahl and uncertainty of a kind of phenol and hydroquinones standard substance.Examination is carried out to raw material, so that purity is qualified, combined using combined gas chromatography mass spectrometry and fourier transform infrared spectroscopy and qualitative confirmation is carried out to testing sample, combined using the method for GC methods, three kinds of different principles of HPLC methods and DSC methods and purity testing is carried out to testing sample, after testing sample is dispensed, uniformity and stability test are carried out again, calculating obtains uncertainty caused by purity testing, uncertainty caused by obtaining uniformity and stability is calculated according to step 4, each uncertainty is carried out into synthesis obtains overall uncertainty.The present invention is qualitative accurate, reduces systematic error, statistical data processing method is rigorous, uncertainty evaluation method is comprehensive, it is ensured that value accuracy, stability and tractability, obtains high-purity phenol and hydroquinones purity rubric material.
Description
Technical field
It is especially a kind of to be used to detect phenol generalization in Freckle removing cosmetics and shampoo the present invention relates to cosmetics detection field
The purity rubric material method of production of compound, phenolic compound refers mainly to phenol and hydroquinones.
Background technology
The accurate detection of additive is most important to the security of cosmetics in cosmetics, because phenol and hydroquinones are
Banned substance in cosmetics, therefore greatly increased for the difficulty of the accurate detection of this kind of trace additives.At present, in cosmetics
The quantitative detection of additive kind uses direct Detection Method mostly, still, in actual application, for same sample, different
The testing result that testing agency provides is not quite similar, or even differs greatly.Compared with n-compound, additive kind in cosmetics
Standard substance not only has typical magnitude accurately measure or strict difinition, moreover it is possible to ensure characteristic magnitude in the special time time limit
With the ability being maintained under storage requirement in prescribed limit, with magnitude tracing, to improve Cosmetic Manufacture, quality control,
The evaluation and confirmation of the detection level and additive kind materials analysis methods of inspection are significant.
The content of the invention
In order to solve problem present in background technology, of the invention proposes a kind of phenol and hydroquinones standard substance
Reinheitszahl and uncertainty assay method, can Accurate Determining phenol and hydroquinones Reinheitszahl, and set up for this is pure
The definite value of angle value carries out Evaluation of Uncertainty.
The present invention is achieved through the following technical solutions：
Step 1：To raw material carry out examination so that purity is qualified and carries out next step, it is qualified after product as to be measured
Sample carries out next step；
Step 2：Combined using gas chromatography-mass spectrometry and fourier transform infrared spectroscopy and testing sample is carried out
Qualitative confirmation；
Step 3：Using based on gas-chromatography (GC) method, high performance liquid chromatography (HPLC) method and means of differential scanning calorimetry (DSC)
The method of three kinds of different principles of method is combined carries out purity testing to testing sample；
Step 4：After testing sample is dispensed, then carry out uniformity and stability test；
Described stability includes short-term stability and long-time stability.
Step 5：Uncertainty caused by obtaining purity testing is calculated according to step 3, is calculated according to step 4 and obtains uniformity
With uncertainty caused by stability, each uncertainty is subjected to synthesis and obtains overall uncertainty.
The step 1：Raw material examination is specially：
The raw material of industry is first subjected to purity initial survey using HPLC methods (see step 3-1.2), judges whether Reinheitszahl is qualified, it is pure
Angle value is not less than 99% and thinks qualified carry out next step, unqualified then to carry out recrystallization processing, until purity is qualified.Now
Product be used as testing sample carry out next step.
The Reinheitszahl is qualified to refer to that purity is not less than 99%.
Described raw material is phenol or hydroquinones.The inventive method for develop include phenol purity rubric material with
Hydroquinones purity rubric material.
The step 2：Qualitative confirmation is specially：
Testing sample is respectively prepared after need testing solution and solid preform, then gas chromatography-mass spectrography is respectively adopted
(GC-MS) method and FFIR (FT-IR) method collect mass spectrogram and infrared spectrogram, mass spectrogram and infrared
Spectrogram is compareed with standard spectrogram, according to matching degree it is qualitative confirmation raw material authenticity, if raw material truly if carry out next step.
Need testing solution is made in testing sample of the purity initial survey after qualified in the step 2 and solid preform is specifically：
For testing sample, on the one hand it is dissolved in pure methanol and need testing solution is made, on the other hand using KBr (KBr) solid preform method
Mixed grinding is simultaneously pressed into solid thin-sheet with mould.
Collecting mass spectrogram using gas chromatography-mass spectrography (GC-MS) method in the step 2 is specifically：
By need testing solution sample introduction into chromatographic column, it is 250 DEG C to set injector temperature, and transmission line temperature is 280 DEG C, is carried
Gas velocity is 1mL/min, and sample size is 10 μ L, and split ratio is 10:1, then using two ladders progressively heating mode, mass spectrum part is equal
Using full scan pattern, scanning range is 12-500m/z, and the solvent delay time is 3min, collects mass spectrogram.
For the need testing solution of phenol, chromatographic column warming temperature is：Using 60 DEG C of initial temperature, keep after 1min, with
15 DEG C/min speed is warming up to 270 DEG C, keeps 10min.
For hydroquinones raw material, chromatographic column warming temperature is：Using 60 DEG C of initial temperature, with 10 DEG C/min speed liter
Temperature is kept after 0.5min to 110 DEG C, then is warming up to 180 DEG C with 10 DEG C/min speed, keeps 3min.
Collecting infrared spectrogram using FFIR (FT-IR) method in the step 2 is specifically：Will
Sample restocking after solid preform is tested using DTGSKBr detectors and KBr beam splitters, and sampling gain is set to 1.0, infrared light
Spectrum scanning range is 4000~400cm-1, Sample Scan 8 times, background scans 8 times, it is 4.000cm to take resolution ratio-1, so as to obtain
Infrared spectrogram.
The step 3：Purity testing is specially：
3-1：For testing sample, it is made after need testing solution, simultaneous determination obtains two groups of purity Value Datas, two groups of purity
Value Data, which is respectively provided with, to carry out repeatedly determining the data obtained；
In processing procedure of the present invention, GC methods and HPLC methods are realized based on mass balance approach (writing a Chinese character in simplified form work " MB ") principle,
Also need to use head space-GC methods, karl Fischer coulomb method and heat respectively again to the impurity that such as dissolvent residual, moisture and ash content are not responding to
Weight analysis method is determined.
3-2：For testing sample, Reinheitszahl is determined using means of differential scanning calorimetry (DSC) method, one group of Reinheitszahl number is obtained
According to this group of purity Value Data, which has, to carry out repeatedly determining the data obtained；
3-3：For each testing sample, repeat step 3-1 and step 3-2 are measured, and will obtain three groups of Reinheitszahl numbers
According to progress data processing obtains the final Reinheitszahl of testing sample.
The step 3-1 is specially：
3-1.1：Chromatogram is gathered using GC methods, chromatogram area normalization method is calculated and obtains the initial of testing sample
Reinheitszahl IGC；
3-1.2：Chromatogram is gathered with HPLC methods, chromatogram area normalization method is calculated and obtains the initial of testing sample
Reinheitszahl IHPLC；
3-1.3：Static Headspace sample introduction-GC- hydrogen flameionizations (FID) detector, karl Fischer coulomb meter is respectively adopted
Testing sample is measured with thermogravimetric analyzer, the degree I of residual solvent is obtained respectivelysolv, moisture percentage
Content Imoi, ash content degree Iash(degree of three kinds of impurity)；
3-1.4：The two initial purity values obtained according to step 3-1.1 and 3-1.2, are obtained through step 3-1.3 respectively
Impurity degree, which is calculated, obtains GC methods and the corresponding two amendment Reinheitszahls I ' of HPLC methods differenceGCAnd I 'HPLC；
3-1.5：Repeat step 3-1.1~3-1.4 takes multiple measurements two groups of purity Value Datas of acquisition.
The step 3-1.1 is specially：
GC method test process after present invention optimization is as follows：By need testing solution sample introduction to low pole chromatographic column DB-1701
In (30m × 0.32mm × 0.25 μm), 280 DEG C of injector temperature, 280 DEG C of fid detector temperature, carrier gas nitrogen flow velocity are set
1mL/min, the μ L of sample size 1, split ratio 2.5：1；Using three ladders, progressively heating mode is operated again, so as to collect chromatogram
Figure, chromatogram is calculated with area normalization method and obtains Reinheitszahl.
For phenol, it is 65 DEG C when column temperature condition setting is initial, 200 DEG C is warming up to 3 DEG C/min speed, then with 10
DEG C/min speed is warming up to 260 DEG C, keeps 6min.The temperature-rise period of phenol is
For hydroquinones, 50 DEG C when column temperature condition setting is initial, 220 DEG C are warming up to 8 DEG C/min speed, then with 15
DEG C/min speed is warming up to 270 DEG C, keeps 6min.The temperature-rise period of hydroquinones is
The present invention compares HP-5 (low pole, 30m × 0.25mm × 0.25 μm), DB-1701 (middle polarity, 30m ×
0.25mm × 0.25 μm), 3 kinds of opposed polarity chromatographic columns of DB-WAX (highly polar, 30m × 0.25mm × 0.25 μm) to impurity and
The separating resulting of principal component, as a result shows, DB-1701 chromatographic columns most beneficial for impurity outflow and detection, and impurity with it is main into
Point theoretical cam curve is higher, separating effect more preferably, the separating effect of HP-2 chromatographic columns takes second place, and DB-WAX chromatographic columns are worst.
The step 3-1.2 is specially：
HPLC method test process after present invention optimization is as follows：
Using C18 chromatographic columns (250mm × 4.6mm × 5 μm), setting sample size is 10 μ L, and column flow is 1mL/min, post
Temperature is 25 DEG C, and the mobile phase acquisition testing wavelength for building raw material is 190nm~400nm 3D data, and wavelength separated degree is
1.2nm.With 271.0nm (phenol) and 289.0nm (hydroquinones) for definite value wavelength, so that chromatogram is collected, by chromatogram
Calculated with area normalization method and obtain Reinheitszahl.
For phenol, flowing phase composition is the pure water of 30% methanol+70%.
For hydroquinones, flowing phase composition is the pure water of 70% methanol+30%.
The present invention compares the methanol of 5 kinds of different proportions on the basis of using C18 chromatographic columns (250mm × 4.6mm × 5 μm)
(A) and pure water (B) be mobile phase (a.10%A+90B%；B.30%A+70%B；C.50%A+50%B；D.70%A+30%B；
E.90%A+10%B) to the influence of impurity and principal component separating resulting, under conditions of impurity and principal component molecular weight are close,
The order appearance of each component polarity size can be ensured.The flowing of the phenol and hydroquinones of the present invention is determined by experimental analysis
Phase composition.
The impurity of low content in phenol can be caused because sample size is too low can not be detected less than the test limit of instrument,
If sample size (or column flow or column temperature) is too high, impurity can be caused to be separated with principal component in phenol not good, and principal component appearance
Peak shape is asymmetric.The concrete technology condition that thus selection sample size of the present invention is 10 μ L.
The step 3-1.3 is specially：
(1) residual solvent degree is determined：
For testing sample, issuable residual solvent species in testing sample is estimated according to technique for producing raw material, according to
The degree of secondary utilization Static Headspace method sample introduction, gas chromatography separation and fid detector method detection assay residual solvent.
Static Headspace sampling system condition determination is：80 DEG C of equilibrium temperature, 90 DEG C of quantitative loop temperature, 110 DEG C of line of transference temperature,
Equilibration time 30min, pressing time 2min；
Gas chromatography condition determination is：Using Agilent DB-624 chromatographic columns, 30m × 0.32mm × 0.50 μm is carried
Gas velocity 1mL/min, split ratio 10:1,200 DEG C of injector temperature originates 40 DEG C of column temperature, 15min is kept, with 10 DEG C/min journeys
Sequence is warming up to 150 DEG C, keeps 10min；
Fid detector testing conditions are：250 DEG C of temperature；Fid detector being detected to, the chromatogram obtained uses external standard method meter
Calculate the concentration value of residual solvent.
(2) moisture percentage assay：
For testing sample, the degree for obtaining moisture is determined with karl Fischer coulomb meter, condition determination is：
It is 20 DEG C to detect environment temperature, and humidity is 40%, and polarizing electrode is DM143-5C, the μ A of polarization current 5.0, is indicated single
Position is voltage (mV), and speed of agitator 45% controls terminal for 100.0mV；The electric current of electrolysis electrode is automatic termination, termination type
Terminated for drift is relative, drift value is 3.0 μ g/min, time range is 0~3600s.
(3) percent ash assay：
For testing sample, the concentration value for obtaining ash content is determined with thermogravimetric analyzer, condition determination is：Using Al2O3Earthenware
Crucible, 650 DEG C are warming up in 25 DEG C of speed with 10 DEG C/min of initial temperature；The mass change in thermal decomposition process is recorded, thermogravimetric is obtained
Curve, the concentration value for exporting ash content is analyzed according to thermogravimetric curve.
The step 3-1.4 is specifically：
I'GC=(100%-Imoi-Isolv-Iash)×IGC
I'HPLC=(100%-Imoi-Isolv-Iash)×IHPLCFormula (1)
In formula, I'GCAnd I'HPLCThe respectively corresponding amendment of gas-chromatography (GC) method and high performance liquid chromatography (HPLC) method is pure
Angle value, I'GCAnd I'HPLCIt is from I by above-mentioned formulaGCAnd IHPLCAmendment is obtained, IGCAnd IHPLCRespectively gas-chromatography (GC) method and
The initial purity value that high performance liquid chromatography (HPLC) method correspondence is obtained, Imoi、IsolvAnd IashRespectively represent moisture, dissolvent residual and
The concentration value of ash content.
The step 3-2 is specially：Differential scanning calorimetry surveys purity, uses 40 μ L standard aluminums crucibles of sky for reference,
Sample weighting amount is 3.24~6.80mg, then progressively heating mode is operated using three ladders, then using purity analysis software
Proteus Analysis obtain Reinheitszahl IDSC, and carry out repeatedly determining two groups of purity Value Datas of acquisition.
For phenol, initial temperature is 0 DEG C, and 20 DEG C are warming up to 5 DEG C/min speed, then with 1 DEG C/min speed liter
Temperature is to 60 DEG C.The temperature-rise period of phenol is
For hydroquinones, initial temperature is 0 DEG C, and 155 DEG C are warming up to 20 DEG C/min speed, then with 10 DEG C/min's
Speed is warming up to 190 DEG C.The temperature-rise period of hydroquinones is
The step 3-3 is specially：
For same testing sample, the three groups of purity Value Datas measured with three kinds of methods are located successively in the following ways
Reason：
3-3.1：(it is repeatedly to determine the Reinheitszahl I' obtained for three groups of purity Value DatasGC, I'HPLCAnd IDSC), respectively
First carry out normal distribution inspection with coefficient of kurtosis method and coefficient of skew method, then with Grabbs methods and Dixon methods carry out from
Group's value, which is examined, rejects dubious value；
3-3.2：(i.e. I' between every two groups of Reinheitszahls of three groups of purity Value DatasGCWith I'HPLCBetween, I'HPLCWith IDSCIt
Between, I'GCWith IDSCBetween) examined with the equally accurate of t methods of inspection progress average value, carry out standard deviation with F methods of inspection
Equally accurate is examined；
3-3.3：According to the equally accurate result of average value and standard deviation, averaged as raw material final purity
Value：
If the purity Value Data that step 3-3.1 retains meets the equally accurate of average value and standard deviation simultaneously, three groups are taken
The arithmetic mean of instantaneous value of purity Value Data；
If the purity Value Data that step 3-3.1 retains meets the unequal accuracy of average value and standard deviation when different, take
The weighted average of three groups of purity Value Datas.
Raw material is dispensed specifically in the step 4：Accurately weighed in the toilet of 20 DEG C ± 3 DEG C of normal temperature to be measured
Sample 50mg or so, is dispensed into brown glass sample bottle, is obtained dispensing sample, is repeated the above steps, and obtains packing sample 200
Bottle, is numbered with number, is preserved under the conditions of refrigeration and lucifuge, for follow-up uniformity and stability test.
It is specially after packing in the step 4：
4-1：Uniformity testing
Respectively from 200 bottles of packing samples according to end to end, middle numbering randomly select 10 bottles of samples, be configured to test sample molten
Liquid, vibration determines Reinheitszahl, every bottle of sample parallel determination 3 times according to HPLC methods (see step 3-1.2)；Single factor test side is used again
Poor analysis method carries out statistical analysis to measurement result, calculates F statistical values, acquisition F critical values of tabling look-up, by comparing F statistical values
With F critical values, the uniformity of packing sample is examined；If F statistical values are less than F critical values, sample is uniform；If F statistical values are more than
Equal to F critical values, then sample is uneven.
F statistical value calculations are as follows：
In formula, SinterAnd SintraRespectively represent bottle between and bottle internal variance, νinterAnd νintraIt is interior certainly with bottle between expression bottle respectively
By spending.
4-2：Stability test
4-2.1 short-term stability
Several bottles are randomly selected from packing sample, is individually placed in 4 DEG C, 20 DEG C and 50 DEG C environment, respectively to the 1st day, the 2nd
My god, after each 1 bottle of taking-up in the 5th day and the 8th day, need testing solution is configured to, is vibrated, is determined according to HPLC methods (see step 3-1.2)
Reinheitszahl, every bottle of sample parallel determination 3 times, averages；The Reinheitszahl measured again with the packing sample being placed in 4 DEG C of environment
For standard, acquisition t critical values of tabling look-up calculate t statistical values ttest, short-term stability is examined by comparing t statistical values and t critical values
Property：If t statistical values are less than t critical values, sample short-term stability；If t statistical values are more than or equal to t critical values, sample is short-term not
It is stable.
T statistical values ttestCalculation formula is as follows：
In formula, x0And s0Purity average value and purity rubric that the packing sample that expression is placed in 4 DEG C of refrigerators respectively is measured
Deviation,Represent to be placed on Reinheitszahl and standard deviation that the packing sample under each different temperatures environment is measured, n tables respectively with s
Show the number of times (now n=3) of parallel determination.
4-2.2 long-time stability
Packing sample is stored in 20 DEG C of environment, the stability of 12 months is carried out using HPLC methods (see step 3-1.2)
Monitoring, according to first close rear thin principle access time node, each timing node chooses 1 sample, each sample parallel determination 3
It is secondary, average；Then in the case where potential kinetics mechanism is unknown, linear fit is carried out using linear model, represented with x
Time, the sample purity value of some timing node is represented with y, fitting is in alignment, sentences using the conspicuousness of the straight slope
The stability of disconnected sample.
By the use of the conspicuousness of the straight slope as stability, the stability for carrying out judgement sample is specifically calculating straight slope
Standard deviation, standard deviation and the t that tables look-up examine critical value be multiplied after and the absolute value of straight slope compared, if straight slope
Absolute value is small, then sample is steady in a long-term；Otherwise sample is unstable for a long time.
The step 5 is to calculate to obtain overall uncertainty in the following ways：
5-1：First GC methods are obtained using following computational methods and HPLC methods determine uncertainty caused by Reinheitszahl：
According to formula (1), I' will be obtained based on GC methods and HPLC methodsGCAnd I'HPLCCalculation formula merge into：
I'GC-HPLC=(100%-Imoi-Isolv-Iash)×IGC-HPLC=f1(IGC-HPLC,Imoi,Isolv,Iash) formula (4)
I' will be obtainedGCAnd I'HPLCUncertainty caused by process merges into a uncertainty and considers u'GC-HPLC, according to
Formula (4), derives its calculation formula as follows：
In formula (5), uGC-HPLCRepresent to obtain IGCAnd IHPLCCaused Composite Seismogram, WithFirst function f is represented respectively1(see formula (4) to IGC-HPLC, Imoi, Isolv, IashSeek partial derivative,
umoi、usolvAnd uashMoisture, dissolvent residual and uncertainty, first function f caused by ash determination are represented respectively1It is expressed as f1
(IGC-HPLC,Imoi,Isolv,Iash)=(100%-Imoi-Isolv-Iash)×IGC-HPLC。
uGC-HPLCCalculation be：uGCAnd uHPLCRepresent to obtain I respectivelyGCAnd IHPLCDraw
The partial uncertainty risen, principal component and the response factor difference of impurity, measurement reproducibility and instrument inspection in testing sample
Survey partial uncertainty caused by limit to obtain through synthesis, response factor difference calculates calibration response factor meter according to effective carbon number method
Calculate and obtain, effective carbon number is equal to the molecular weight of component (principal component or impurity) and the carbon atom number contained in the component molecular
The ratio between；umoi、usolvAnd uashRespectively in terms of moisture, dissolvent residual and the repeatability of ash determination.
5-2：DSC methods are calculated using below equation again and determine uncertainty u caused by ReinheitszahlDSC：
Wherein, uDSC-AAnd uDSC-BRepresent the standard uncertainty of type A evaluation and type B evaluation in DSC methods measure, uDSC-AIt is
Obtained by the repeatability calculating for measuring DSC methods；
For uDSC-B, because the principle that DSC methods determine purity is to be based on van' t Hoff equation, the equation is as follows：
IDSCThe Reinheitszahl of DSC method determination samples is represented, y represents the molar fraction of impurity, T0And TmPure sample product are represented respectively
With the melting temperature of actual sample, △ HfMole melting enthalpy is represented, R is gas constant, and Q is the heat that sample absorbs, and m is sample
Quality, M be sample molal weight.
Therefore, uDSC-BComputational methods it is as follows：
Wherein, um, uQ, uTRespectively the weighing error of balance, the calorimetry error of instrument, the temperature error of instrument this
The standard uncertainty of three mutual incoherent input quantities,Second function f is represented respectively2
To m, Q, T0, TmAsk partial derivative, c1, c2, c3The calculated value of quality, heat and temperature is represented respectively；
Second function f2It is expressed as：
In formula, T0And TmThe melting temperature of pure sample product and actual sample is represented respectively, and R is gas constant, and Q absorbs for sample
Heat, m be sample quality, M be sample molal weight.
5-3：Calculate a point uncertainty
The one-way analysis of variance result obtained according to uniformity testing obtains uniformity using below equation calculating and caused
Uncertainty uH：
The standard deviation for examining obtained fitting a straight line slope according to long-time stability is multiplied by the STABILITY MONITORING time, is used
Below equation calculates and obtains uncertainty u caused by stabilitys：
uS=s (b1) t formula (10)
5-4：Calculate overall uncertainty
GC methods, HPLC methods and DSC methods are determined by uncertainty caused by purity using below equation, and uniformity and steady
Uncertainty carries out COMPREHENSIVE CALCULATING and obtains overall uncertainty caused by qualitative, and formula is as follows：
Wherein, uHRepresent uncertainty, u caused by uniformitySRepresent uncertainty, u' caused by stabilityGC-HPLCRepresent
GC methods and HPLC methods obtain Composite Seismogram, u caused by purity correction valueDSCRepresent that DSC methods are determined not true caused by Reinheitszahl
Fixed degree.
Purity initial survey in the step 1 and the Reinheitszahl in the uniformity and stability test of the step 4 determine equal
With the step 3-1.2 identical processes.
The present invention passes through raw material screening, qualitative confirmation, purity testing, uniformity and stability test and uncertainty
Calculate, obtain the standard substance of know clearly phenol and hydroquinones, so as to improve the degree of accuracy that aldehydes matter is detected in cosmetics, together
When ensure testing result traceability.
The beneficial effects of the invention are as follows：
The present invention can Accurate Determining phenol and hydroquinones Reinheitszahl, and set up for the Reinheitszahl definite value obtain not
The mode of degree of certainty.
The present invention is qualitative accurate comprehensive, and three kinds of method for detecting purity reduce the system brought by single valued methods and missed
Difference, uniformity, stability and uncertainty evaluation method system are comprehensive, it is ensured that value accuracy, stability and tractability,
Obtain high-purity (more than 99%) phenol and hydroquinones purity rubric material.
Measurement result of the present invention can obtain phenol and hydroquinones purity rubric material, and be caused by purity rubric material
The testing result of respective additive is more accurate in cosmetics, and the magnitude tracing and value available for respective substance testing result are passed
Pass, the quality control in analysis method and the evaluation of detectability and production process.
Brief description of the drawings
Fig. 1 is the inventive method FB(flow block)；
Fig. 2 is the mass spectrogram for the phenol that embodiment 1 is collected；
Fig. 3 is the infrared spectrogram for the phenol that embodiment 1 is collected；
Fig. 4 is the gas chromatogram for the phenol that embodiment 1 is collected；
Fig. 5 is the liquid chromatogram for the phenol that embodiment 1 is collected；
Fig. 6 is the differential scanning calorimetry curve map for the phenol that embodiment 1 is collected；
Fig. 7 is the mass spectrogram for the hydroquinones that embodiment 2 is collected；
Fig. 8 is the infrared spectrogram for the hydroquinones that embodiment 2 is collected；
Fig. 9 is the liquid chromatogram for the hydroquinones that embodiment 2 is collected；
Figure 10 is the gas chromatogram for the hydroquinones that embodiment 2 is collected；
Figure 11 is the differential scanning calorimetry curve map for the hydroquinones that embodiment 2 is collected.
Embodiment
The invention will be further described with reference to the accompanying drawings and examples.
Embodiments of the invention are as follows：
Embodiment 1：Phenol
Step 1 --- raw material screening
The starting phenol produced using lark prestige Science and Technology Ltd..Surveyed with HPLC methods (see the step 3-1.2 of embodiment 1)
Determine Reinheitszahl, obtained after recrystallization 2 times purity initial survey it is qualified after testing sample.
Step 2 --- qualitative confirmation
With GC-MS methods and the legal confirmation phenol of FT-IR.
Step 2-1, using the legal confirmation phenol of GC-MS
For phenol testing sample, it is dissolved in after methanol and need testing solution is made, sample introduction test.Test condition is as follows：Set
Injector temperature is 250 DEG C, and transmission line temperature is 280 DEG C, and flow rate of carrier gas is 1mL/min, and sample size is 10 μ L, and split ratio is
10:1；Chromatographic column warming temperature is：Using 60 DEG C of initial temperature, keep after 1min, 270 are warming up to 15 DEG C/min speed
DEG C, keep 10min.
It can be obtained by accompanying drawing 1, molecular ion peak 94, phenol Standard mass spectrogram is obtained through NIST standard spectrogram library searchings, the two
It is 96% with degree.
Step 2-2, using the legal confirmation phenol of FT-IR
For phenol testing sample, using solid thin-sheet is pressed into after KBr mixed grindings with mould, restocking is tested.Test
Condition is as follows：Tested using DTGS KBr detectors and KBr beam splitters, sampling gain is set to 1.0, IR spectrum scanning scope
For 4000~400cm-1, Sample Scan 8 times, background scans 8 times, it is 4.000cm to take resolution ratio-1, so as to obtain infrared spectrogram
(see accompanying drawing 2).
It can be obtained by accompanying drawing 2, ν=3355.44cm-1(1) roomy absworption peak is the phenolic hydroxyl group O-H easily associated near
Stretching vibration peak, ν=3090.03cm-1(2), ν=3046.04cm-1(3), ν=3020.22cm-1(4) be on phenyl ring not
The stretching vibration peak of saturation c h bond, ν=1599.81cm-1(5), ν=1499.28cm-1(6) be phenyl ring skeletal vibration, ν
=1231.12cm-1(7) be C-O in phenolic hydroxyl group stretching vibration peak, ν=752.99cm-1And ν=690.54cm (8)-1(9), it is
Mono-substituted c h bond flexural vibrations peak on phenyl ring.Phenol Standard infrared spectrogram is obtained through standard spectrogram library searching, the two matching degree
For 94%.
Step 3 --- purity testing
Phenol purity is determined with GC methods, HPLC methods and DSC methods.
Step 3-1, the testing sample for phenol, are dissolved in pure methanol, need testing solution are made, using GC methods and HPLC methods
Simultaneous determination Reinheitszahl；The impurity that dissolvent residual, moisture and ash content are not responding to is again respectively with head space-GC methods, karl Fischer coulomb
Method and thermogravimetry are determined.
Step 3-1.1, using GC methods gather chromatogram, optimization acquisition condition it is as follows：
Compare HP-5 (low pole, 30m × 0.25mm × 0.25 μm), DB-1701 (middle polarity, 30m × 0.25mm ×
0.25 μm), 3 kinds of opposed polarity chromatographic columns of DB-WAX (highly polar, 30m × 0.25mm × 0.25 μm) to impurity and principal component
Separating resulting, as a result shows, DB-1701 chromatographic columns are most beneficial for the outflow and detection of impurity, and the theory of impurity and principal component
The number of plates is higher, separating effect more preferably, therefore selects low pole chromatographic column DB-1701 (30m × 0.32mm × 0.25 μm).
280 DEG C of injector temperature of setting, 280 DEG C of fid detector temperature, carrier gas nitrogen flow velocity 1mL/min, the μ L of sample size 1,
Split ratio 2.5：1；Chromatographic column temperature-rise period is
The chromatogram collected (see accompanying drawing 3) is calculated into acquisition initial purity value with area normalization method and (uses IGCRepresent).In accompanying drawing 3,
Peak 1 is solvent peak, and peak 2 is phenol, and peak 3 is impurity, and curve b is curve a enlarged drawing.
Step 3-1.2, using HPLC methods gather chromatogram, optimization acquisition condition it is as follows：
The methanol (A) and pure water (B) of 5 kinds of different proportions are compared for mobile phase (a.10%A+90B%；B.30%A+
70%B；C.50%A+50%B；D.70%A+30%B；E.90%A+10%B) to impurity and principal component separating degree, theoretical tray
Number, peak width, the influence of symmetrical sexual factor, it is determined that it is the 30% pure pure water of methanol+70% to build flowing phase composition, using C18 chromatograms
Post (250mm × 4.6mm × 5 μm), setting sample size is 10 μ L, and column flow is 1mL/min, and column temperature is 25 DEG C, acquisition testing ripple
A length of 190nm~400nm 3D data, using 271.0nm phenol as definite value wavelength, the chromatogram collected (see accompanying drawing 4) is used
Area normalization method calculates acquisition initial purity value and (uses IHPLCRepresent).Peak 1 and peak 2 are impurity in accompanying drawing 4, and peak 3 is phenol, bent
Line b is curve a enlarged drawing.
Step 3-1.3, Static Headspace sample introduction-GC- hydrogen flameionizations (FID) detector, karl Fischer storehouse is respectively adopted
Logical sequence instrument and thermogravimetric analyzer are measured to testing sample, and residual solvent, moisture, the percentage of three kinds of impurity of ash content are obtained respectively
Than content (I is used respectivelysolv, ImoiAnd IashRepresent).Specific condition determination is as follows：
(1) residual solvent degree is determined：
For testing sample, according to technique for producing raw material, issuable residual solvent species is in estimation testing sample
Acetone, successively with Static Headspace method sample introduction, gas chromatography separation and fid detector method detection collection chromatogram.
Static Headspace sampling system condition determination is：80 DEG C of equilibrium temperature, 90 DEG C of quantitative loop temperature, 110 DEG C of line of transference temperature,
Equilibration time 30min, pressing time 2min；
Gas chromatography condition determination is：Using Agilent DB-624 chromatographic columns, 30m × 0.32mm × 0.50 μm is carried
Gas velocity 1mL/min, split ratio 10:1,200 DEG C of injector temperature originates 40 DEG C of column temperature, 15min is kept, with 10 DEG C/min journeys
Sequence is warming up to 150 DEG C, keeps 10min；
Fid detector testing conditions are：250 DEG C of temperature；
The standard curve of pure acetone solvent is set up according to said determination condition, the percentage for calculating acetone with external standard method contains
Amount (uses IsolvRepresent).
(2) moisture percentage assay：
For testing sample, the degree of moisture is determined with karl Fischer coulomb meter, condition determination is：
It is 20 DEG C to detect environment temperature, and humidity is 40%, and polarizing electrode is DM143-5C, the μ A of polarization current 5.0, is indicated single
Position is voltage (mV), and speed of agitator 45% controls terminal for 100.0mV；The electric current of electrolysis electrode is automatic termination, termination type
Terminated for drift is relative, drift value is 3.0 μ g/min, time range is 0~3600s.The moisture percentage content I of acquisitionmoi
Represent.
(3) percent ash assay：
For testing sample, the concentration value for obtaining ash content is determined with thermogravimetric analyzer, condition determination is：Using Al2O3
Crucible, 650 DEG C are warming up in 25 DEG C of speed with 10 DEG C/min of initial temperature；The mass change in thermal decomposition process is recorded, heat is obtained
Weight curve, (I is used according to the degree that thermogravimetric curve analyzes output ash contentashRepresent).
3-1.4, the Reinheitszahl obtained according to step 3-1.1 and 3-1.2, the impurity percentage obtained respectively through step 3-1.3
Than content, acquisition amendment Reinheitszahl is calculated according to formula (1) and (uses I' respectivelyGCAnd I'HPLCRepresent).
Step 3-2, the testing sample for phenol, phenol Reinheitszahl is determined using DSC methods.Condition determination is as follows：
Use 40 μ L standard aluminums crucibles of sky for reference, sample weighting amount is 3.24~6.80mg, temperature-rise period isDSC curve (see accompanying drawing 5) is gathered, curve is carried out using software
Purity analysis obtains Reinheitszahl and (uses IDSCRepresent).
Step 3-3 is for the testing sample of each phenol, and repeat step 3-1 and step 3-2 carry out 10 measure, obtain 10
It is secondary to determine corresponding three groups of Reinheitszahls, carry out the final Reinheitszahl that data processing obtains testing sample.
Step 3-3.1
3-3.1：For three groups of Reinheitszahl (I'GC, I'HPLCAnd IDSC), coefficient of kurtosis method and coefficient of skew method are first used respectively
Normal distribution inspection is carried out, then outlier inspection is carried out with Grabbs methods and Dixon methods, as a result shows no dubious value, protects
Residual is according to progress next step；
3-3.2：For every two groups of Reinheitszahl (I'GCWith I'HPLC, I'HPLCWith IDSC, I'GCWith IDSC) equally accurate inspection is carried out,
T assays show that the average value of three groups of data is equally accurate, and F assays show that the standard deviation of three groups of data is to wait essence
Degree；
3-3.3：Data processed result is shown in Table 1.Because three groups of data determine for equally accurate, then the arithmetic of three groups of Reinheitszahls is taken
Average value is final Reinheitszahl, is：
1 three kinds of methods of table determine phenol Reinheitszahl result
Step 4 --- packing
It is accurate in the toilet of 20 DEG C ± 3 DEG C of normal temperature to weigh phenol 50mg or so, dispense into brown glass sample bottle,
Packing sample is obtained, is repeated the above steps, about 200 bottles of sample of packing is obtained, is numbered with number, protected under the conditions of refrigeration and lucifuge
Deposit.For uniformity and stability test.
Step 5 --- uniformity testing
Phenol uniformity testing the results are shown in Table 2.Statistical analysis is carried out to data using one-way analysis of variance method, according to
Formula (2) is obtainedI.e. F statistical values are 2.24, look into F and examine and face
Dividing value table is understood：F0.05 (9,20)=2.39, i.e. F critical values are 2.39, therefore F statistical values<F critical values, show the packing of phenol
Sample has preferable uniformity.
The phenol uniformity testing result of table 2
Step 6 --- stability test
Step 6-1 short-term stabilities are examined
The short-term stability assay of the phenol of table 3
The short-term stability assay of phenol is shown in Table 3.The Reinheitszahl measured with the packing sample being placed in 4 DEG C of environment
For standard.Obtained by table 3, purity rubric value is x0=99.60%, its relative standard deviation is s0=0.03%, parallel determination time
Number n=3, free degree ν=n+n-2=4.Substitution formula (3) calculating obtains t statistical values and (uses ttestRepresent).Look into t distribution bilateral separates
Knowable to digit table, t(0.05,4)=2.78.Obtained by table 3, under the conditions of 20 DEG C, ttest<t(0.05,4), under the conditions of 50 DEG C, ttest>
t(0.05,4), show that packing sample is good in ordinary temperature stability, and the Reinheitszahl for dispensing sample under the high temperature conditions occurs significantly to decline
Subtract, therefore packing sample need to be preserved at normal temperatures.
Step 6-2 long-time stability are examined
The long-time stability assay of the phenol of table 4
The long-time stability assay of phenol is shown in Table 4.If the time is y=b to the equation of Reinheitszahl0+b1X, the mark of slope
Quasi- deviation is s (b1), obtained through regression analysis | b1|=8.6 × 10-3, s (b1)=3.78 × 10-3, examine tables of critical values to obtain through looking into t
t(0.95,4)=2.78, then | b1|<t0.95,4·s(b1), then slop estimation value is not notable, shows when confidence level is 0.95, point
Significant changes do not occur for the Reinheitszahl of dress sample.
Step 7 --- uncertainty evaluation
Uncertainty evaluation caused by step 7-1 purity testings
Three kinds of methods carry out uncertainty result caused by purity testings it is as shown in the table (table 5：GC methods and HPLC methods；Table 6：
DSC methods).
The GC methods of table 5 and HPLC methods determine uncertainty caused by purity
Uncertainty caused by the DSC method purity testings of table 6
The uncertainty that purity testing is introduced (uses uDRepresent), by the uncertainty combination of three kinds of methods, then obtain：
The uncertainty evaluation that step 7-2 uniformities and stability are introduced
According to uniformity testing result and formula (9), the partial uncertainty for obtaining uniformity introducing is：According to stability test result and formula (10), term of validity t=12 months
The uncertainty of long-time stability is：uS=s (b1) t=4.5 × 10-2%
Step 8 --- conclusion
Obtained according to step 3, the purity rubric value of phenol is 99.42%, according to step 7 and formula (11) stardard uncertairty
Spend for 0.10%, expanded uncertainty is 0.20%, k=2.The uniformity that is stored within the time of being valid for one year, under normal temperature and
Have good stability, Accurate Determining, transmission of quantity value and the magnitude tracing of phenol in cosmetics can be used for as purity rubric material.
Through Subscriber Unit, (Shenzhen leads in detection technique Co., Ltd, Shenzhen the phenol purity rubric material of the present embodiment
Examine joint inspection and survey Co., Ltd and Hangzhou environmental monitoring central station) it is on probation after, provided user's trial report, trial report table
Show, the Certified Reference Material Homogeneity is good, and value is accurately and reliably, easy to use, meet phenol degree in cosmetics accurate
The requirement really determined, with very high practical value and promotional value.
Embodiment 2：Hydroquinones
Step 1 raw material screening
The hydroquinones raw material produced by commercially available use lark prestige Science and Technology Ltd..With HPLC methods (see implementation
The step 3-1.2 of example 2) determine Reinheitszahl, recrystallization 3 times after obtain purity initial survey it is qualified after testing sample.
Step 2 --- qualitative confirmation
With GC-MS methods and the legal confirmation hydroquinones of FT-IR.
Step 2-1, using the legal confirmation hydroquinones of GC-MS
For hydroquinones testing sample, it is dissolved in after methanol and need testing solution is made, sample introduction test.Test condition is as follows：
It is 250 DEG C to set injector temperature, and transmission line temperature is 280 DEG C, and flow rate of carrier gas is 1mL/min, and sample size is 10 μ L, split ratio
For 10:1；Chromatographic column warming temperature is：Chromatographic column warming temperature is：Using 60 DEG C of initial temperature, with 10 DEG C/min speed liter
Temperature is kept after 0.5min to 110 DEG C, then is warming up to 180 DEG C with 10 DEG C/min speed, 3min is kept, using full scan mode
Scanning, scanning range is 12-500m/z, and the solvent delay time is 3min.The mass spectrogram collected is compareed with standard mass spectrogram, is obtained
To matching degree 95%, it is real (see accompanying drawing 6) to show testing sample.
It can be obtained by accompanying drawing 6, molecular ion peak 119.9, hydroquinones standard mass spectrogram is obtained through standard spectrogram library searching, the two
Matching degree is 95%.
Step 2-2, using the legal confirmation hydroquinones of FT-IR
For hydroquinones testing sample, using solid thin-sheet is pressed into after KBr mixed grindings with mould, restocking is tested.
Test condition is as follows：
Tested using DTGS KBr detectors and KBr beam splitters, sampling gain is set to 1.0, IR spectrum scanning scope
For 4000~400cm-1, Sample Scan 8 times, background scans 8 times, it is 4.000cm to take resolution ratio-1, so as to obtain infrared spectrogram
(see accompanying drawing 7).
It can be obtained by accompanying drawing 7, ν=3261.34cm-1(1) the roomy absworption peak in place is the phenolic hydroxyl group O-H easily associated
Stretching vibration peak.ν=3030.11cm-1(2) be unsaturated c h bond on phenyl ring stretching vibration peak.ν=1517.92cm-1(3),
ν=1475.25 (4) are the skeletal vibration of phenyl ring, ν=1242.99cm-1(5), ν=1209.42cm-1(6), ν=
1191.72cm-1(7) be C-O in phenolic hydroxyl group stretching vibration peak, ν=827.22cm-1(8) it is the dibasic C- of 1,4- on phenyl ring
H bond bending vibration peaks.After being compareed with standard spectrogram, matching degree is 94%.
Step 3 --- purity testing
Hydroquinones purity is determined with GC methods, HPLC methods and DSC methods.
Step 3-1, the testing sample for hydroquinones, are dissolved in pure methanol, need testing solution are made, using GC methods and
HPLC method simultaneous determination Reinheitszahls；The impurity that dissolvent residual, moisture and ash content are not responding to uses head space-GC methods, karr expense respectively again
Not coulomb method and thermogravimetry are determined.
Step 3-1.1, using GC methods gather chromatogram, optimization acquisition condition it is as follows：
Compare HP-5 (low pole, 30m × 0.25mm × 0.25 μm), DB-1701 (middle polarity, 30m × 0.25mm ×
0.25 μm), 3 kinds of opposed polarity chromatographic columns of DB-WAX (highly polar, 30m × 0.25mm × 0.25 μm) to impurity and principal component
Separating resulting, as a result shows, DB-1701 chromatographic columns are most beneficial for the outflow and detection of impurity, and the theory of impurity and principal component
The number of plates is higher, separating effect more preferably, therefore selects low pole chromatographic column DB-1701 (30m × 0.32mm × 0.25 μm).
280 DEG C of injector temperature of setting, 280 DEG C of fid detector temperature, carrier gas nitrogen flow velocity 1mL/min, the μ L of sample size 1,
Split ratio 2.5：1；Chromatographic column temperature-rise period is
The chromatogram collected (see accompanying drawing 8) is calculated into acquisition initial purity value with area normalization method and (uses IGCRepresent).
In accompanying drawing 8, peak 1 is solvent, and peak 2 is hydroquinones, and peak 3 is impurity.Curve b is curve a enlarged drawing.
Step 3-1.2, using HPLC methods gather chromatogram, optimization acquisition condition it is as follows：
The methanol (A) and pure water (B) of 5 kinds of different proportions are compared for mobile phase (a.10%A+90B%；B.30%A+
70%B；C.50%A+50%B；D.70%A+30%B；E.90%A+10%B) to impurity and principal component separating degree, theoretical tray
Number, peak width, the influence of symmetrical sexual factor, it is determined that it is the 70% pure pure water of methanol+30% to build flowing phase composition, using C18 chromatograms
Post (250mm × 4.6mm × 5 μm), setting sample size is 10 μ L, and column flow is 1mL/min, and column temperature is 25 DEG C, acquisition testing ripple
A length of 190nm~400nm 3D data, using 289.0nm phenol as definite value wavelength, the chromatogram collected (see accompanying drawing 9) is used
Area normalization method calculates acquisition initial purity value and (uses IHPLCRepresent).
In accompanying drawing 9, peak 1, peak 3 and peak 4 are impurity, and peak 2 is hydroquinones.Curve b is curve a enlarged drawing.
Step 3-1.3, Static Headspace sample introduction-GC- hydrogen flameionizations (FID) detector, karl Fischer storehouse is respectively adopted
Logical sequence instrument and thermogravimetric analyzer are measured to testing sample, and residual solvent, moisture, the percentage of three kinds of impurity of ash content are obtained respectively
Than content (I is used respectivelysolv, ImoiAnd IashRepresent).Specific condition determination is as follows：
(1) residual solvent degree is determined：
For testing sample, according to technique for producing raw material, issuable residual solvent species is in estimation testing sample
Acetone, successively with Static Headspace method sample introduction, gas chromatography separation and fid detector method detection collection chromatogram.
Static Headspace sampling system condition determination is：80 DEG C of equilibrium temperature, 90 DEG C of quantitative loop temperature, 110 DEG C of line of transference temperature,
Equilibration time 30min, pressing time 2min；
Gas chromatography condition determination is：Using Agilent DB-624 chromatographic columns, 30m × 0.32mm × 0.50 μm is carried
Gas velocity 1mL/min, split ratio 10:1,200 DEG C of injector temperature originates 40 DEG C of column temperature, 15min is kept, with 10 DEG C/min journeys
Sequence is warming up to 150 DEG C, keeps 10min；
Fid detector testing conditions are：250 DEG C of temperature；
The standard curve of pure acetone solvent is set up according to said determination condition, the percentage for calculating acetone with external standard method contains
Amount (uses IsolvRepresent).
(2) moisture percentage assay：
For testing sample, the degree of moisture is determined with karl Fischer coulomb meter, condition determination is：
It is 20 DEG C to detect environment temperature, and humidity is 40%, and polarizing electrode is DM143-5C, the μ A of polarization current 5.0, is indicated single
Position is voltage (mV), and speed of agitator 45% controls terminal for 100.0mV；The electric current of electrolysis electrode is automatic termination, termination type
Terminated for drift is relative, drift value is 3.0 μ g/min, time range is 0~3600s.The moisture percentage content I of acquisitionmoi
Represent.
(3) percent ash assay：
For testing sample, the concentration value for obtaining ash content is determined with thermogravimetric analyzer, condition determination is：Using Al2O3
Crucible, 650 DEG C are warming up in 25 DEG C of speed with 10 DEG C/min of initial temperature；The mass change in thermal decomposition process is recorded, heat is obtained
Weight curve, (I is used according to the degree that thermogravimetric curve analyzes output ash contentashRepresent).
3-1.4, the Reinheitszahl obtained according to step 3-1.1 and 3-1.2, the impurity percentage obtained respectively through step 3-1.3
Than content, acquisition amendment Reinheitszahl is calculated according to formula (1) and (uses I' respectivelyGCAnd I'HPLCRepresent).
Step 3-2, the testing sample for hydroquinones, hydroquinones Reinheitszahl is determined using DSC methods.Condition determination is such as
Under：
Use 40 μ L standard aluminums crucibles of sky for reference, sample weighting amount is 3.24~6.80mg, temperature-rise period isDSC curve (see accompanying drawing 10) is gathered, curve is carried out using software
Purity analysis obtains Reinheitszahl and (uses IDSCRepresent).
Step 3-3 is for the testing sample of each hydroquinones, and repeat step 3-1 and step 3-2 carry out 10 measure, obtained
Obtain 10 times and determine corresponding three groups of Reinheitszahls, carry out the final Reinheitszahl that data processing obtains testing sample.
Step 3-3.1
3-3.1：For three groups of Reinheitszahl (I'GC, I'HPLCAnd IDSC), coefficient of kurtosis method and coefficient of skew method are first used respectively
Normal distribution inspection is carried out, then outlier inspection is carried out with Grabbs methods and Dixon methods, as a result shows no dubious value, protects
Residual is according to progress next step；
3-3.2：For every two groups of Reinheitszahl (I'GCWith I'HPLC, I'HPLCWith IDSC, I'GCWith IDSC) equally accurate inspection is carried out,
T assays show that the average value of three groups of data is equally accurate, and F assays show that the standard deviation of three groups of data is to wait essence
Degree；
3-3.3：Data processed result is shown in Table 7.Because three groups of data determine for equally accurate, then the arithmetic of three groups of Reinheitszahls is taken
Average value is final Reinheitszahl, is：
7 three kinds of methods of table determine hydroquinones Reinheitszahl result
Step 4 --- packing
It is accurate in the toilet of 20 DEG C ± 3 DEG C of normal temperature to weigh hydroquinones 50mg or so, packing to brown glass sample
In bottle, packing sample is obtained, is repeated the above steps, obtained about 200 bottles of sample of packing, be numbered with number, in refrigeration and lucifuge condition
It is lower to preserve.For uniformity and stability test.
Step 5 --- uniformity testing
The uniformity testing of hydroquinones the results are shown in Table 8.Statistical is carried out to data using one-way analysis of variance method
Analysis, is obtained according to formula (2)I.e. F statistical values are 1.70, look into F
Tables of critical values is examined to understand：F0.05 (9,20)=2.39, i.e. F critical values are 2.39, therefore F statistical values<F critical values, show phenol
Packing sample there is preferable uniformity.
The uniformity testing result of the hydroquinones of table 8
Step 6 --- stability test
Step 6-2 short-term stabilities are examined
The short-term stability assay of the hydroquinones of table 9
The short-term stability assay of hydroquinones is shown in Table 9, with the packing sample being placed in 4 DEG C of environment measure it is pure
Angle value is standard.Obtained by table 3, purity rubric value is x0=99.74%, its relative standard deviation is s0=0.01%, parallel determination
Frequency n=3, free degree ν=n+n-2=4.Substitution formula (3) calculating obtains t statistical values and (uses ttestRepresent).Look into t distribution bilaterals
Knowable to Table, t(0.05,4)=2.78.Obtained by table 9, under the conditions of 20 DEG C, ttest<t(0.05,4), under the conditions of 50 DEG C, ttest>
t(0.05,4), show that packing sample is good in ordinary temperature stability, and the Reinheitszahl for dispensing sample under the high temperature conditions occurs significantly to decline
Subtract, therefore packing sample need to be preserved at normal temperatures.
Step 6-2 long-time stability are examined
The long-time stability of the hydroquinones of table 10 investigate result
The long-time stability of hydroquinones are investigated and the results are shown in Table 10.If the time is y=b to the equation of Reinheitszahl0+b1X, tiltedly
The standard deviation of rate is s (b1), obtained through regression analysis | b1|=2.3 × 10-3, s (b1)=2.8 × 10-3, examine critical through looking into t
Value table obtains t(0.95,n-2)=2.78, then | b1|<t0.95,n-2·s(b1), then slop estimation value is not notable, shows when confidence level is
When 0.95, significant changes do not occur for the Reinheitszahl of packing sample.
Step 7 --- uncertainty evaluation
The uncertainty evaluation that step 7-1 definite values are introduced
Uncertainty evaluation caused by step 7-1 purity testings
Step 7-1.1GC methods and HPLC methods determine caused uncertainty
Three kinds of methods carry out uncertainty result caused by purity testings it is as shown in the table (table 11：GC methods and HPLC methods；Table
12：DSC methods).
The GC methods of table 11 and HPLC methods determine uncertainty result caused by purity
Uncertainty caused by the DSC methods of table 12
Uncertainty caused by purity testing (is used into uDRepresent) by the uncertainty combination of three kinds of method for detecting purity, then
Obtain：
The uncertainty evaluation that step 7-2 uniformities and stability are introduced
According to uniformity testing result and formula (9), obtaining partial uncertainty caused by uniformity is：According to stability test result and formula (10), term of validity t=12 months
The uncertainty of long-time stability is：uS=s (b1) t=3.4 × 10-2%
Step 8 --- conclusion
Obtained according to step 3, the standard purity value of hydroquinones is 99.65%, is marked according to step 7 and formula (11)
Quasi- uncertainty is 0.09%, and expanded uncertainty is 0.18%, k=2.Stored within the time of being valid for one year, under normal temperature
Uniformity and have good stability, the Accurate Determining of hydroquinones, transmission of quantity value in cosmetics can be used for as purity rubric material
And magnitude tracing.
Through Subscriber Unit, (Shenzhen leads to detection technique Co., Ltd, depth to the hydroquinones purity rubric material of the present embodiment
Joint inspection is examined in ditch between fields and surveys Co., Ltd and Hangzhou environmental monitoring central station) it is on probation after, provided user's trial report, trial report
Represent, the Certified Reference Material Homogeneity is good, and value is accurately and reliably, easy to use, meets hydroquinones percentage in cosmetics
The requirement of content Accurate Determining, with very high practical value and promotional value.
As seen from the above-described embodiment, the inventive method is qualitative accurate, with the method simultaneous determination of three kinds of different principles
Reinheitszahl, is reduced because of the systematic error that single valued methods are brought, statistical data processing method is rigorous, uncertainty evaluation side
Method is comprehensive, it is ensured that value accuracy, stability and tractability, obtains high-purity (more than 99%) phenol and hydroquinones
Purity rubric material.
Claims (10)
1. the assay method of the Reinheitszahl and uncertainty of a kind of phenol and hydroquinones standard substance, it is characterised in that：
Step 1：Examination is carried out to raw material so that purity is qualified and carries out next step；
Step 2：Combine qualitative to testing sample progress using gas chromatography-mass spectrometry and fourier transform infrared spectroscopy
Confirmation；
Step 3：Using based on gas-chromatography (GC) method, high performance liquid chromatography (HPLC) method and means of differential scanning calorimetry (DSC) method three
The method for planting different principle is combined to testing sample progress purity testing；
Step 4：After testing sample is dispensed, then carry out uniformity and stability test；
Step 5：Uncertainty caused by obtaining purity testing is calculated according to step 3, is calculated according to step 4 and obtains uniformity and steady
Uncertainty caused by qualitative, carries out synthesis by each uncertainty and obtains overall uncertainty.
2. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 1 and hydroquinones standard substance
Method, it is characterised in that：The step 1：Raw material examination is specially：The raw material of industry is first subjected to purity initial survey using HPLC methods, sentenced
Whether disconnected Reinheitszahl is qualified, and Reinheitszahl is not less than 99% and thinks qualified carry out next step, unqualified then to carry out at recrystallization
Reason, until purity is qualified.
3. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 1 and hydroquinones standard substance
Method, it is characterised in that：The step 2：Qualitative confirmation is specially：Need testing solution and solid preform is respectively prepared in testing sample
Afterwards, then gas chromatography-mass spectrography (GC-MS) method is respectively adopted and FFIR (FT-IR) method is collected
Mass spectrogram and infrared spectrogram, mass spectrogram and infrared spectrogram are compareed with standard spectrogram, according to the qualitative confirmation raw material of matching degree
Authenticity, if raw material truly if carry out next step.
4. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 1 and hydroquinones standard substance
Method, it is characterised in that：The step 3：Purity testing is specially：
3-1：For testing sample, it is made after need testing solution, simultaneous determination obtains two groups of purity Value Datas；
3-2：For testing sample, Reinheitszahl is determined using means of differential scanning calorimetry (DSC) method, one group of purity Value Data is obtained；
3-3：For each testing sample, repeat step 3-1 and step 3-2 are measured, and will be obtained three groups of purity Value Datas, are entered
Row data processing obtains the final Reinheitszahl of testing sample.
5. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 4 and hydroquinones standard substance
Method, it is characterised in that：The step 3-1 is specifically included：
3-1.1：Chromatogram is gathered using GC methods, chromatogram area normalization method is calculated to the initial purity for obtaining testing sample
Value IGC；
3-1.2：Chromatogram is gathered with HPLC methods, chromatogram area normalization method is calculated to the initial purity for obtaining testing sample
Value IHPLC；
3-1.3：Static Headspace sample introduction-GC- hydrogen flameionizations (FID) detector, karl Fischer coulomb meter and heat is respectively adopted
Weight analysis instrument is measured to testing sample, and the degree I of residual solvent is obtained respectivelysolv, moisture degree
Imoi, ash content degree Iash；
3-1.4：The two initial purity values obtained according to step 3-1.1 and 3-1.2, the impurity obtained respectively through step 3-1.3
Degree, which is calculated, obtains GC methods and the corresponding two amendment Reinheitszahls I ' of HPLC methods differenceGCAnd I 'HPLC；
3-1.5：Repeat step 3-1.1~3-1.4 takes multiple measurements two groups of purity Value Datas of acquisition.
6. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 5 and hydroquinones standard substance
Method, it is characterised in that：The step 3-1 is specially further：
Step 3-1.1：
By need testing solution sample introduction into low pole chromatographic column DB-1701 (30m × 0.32mm × 0.25 μm), injection port temperature is set
280 DEG C of degree, 280 DEG C of fid detector temperature, carrier gas nitrogen flow velocity 1mL/min, the μ L of sample size 1, split ratio 2.5：1；Three are used again
Progressively heating mode is operated ladder, so as to collect chromatogram, chromatogram is calculated with area normalization method and obtains purity
Value；
Wherein, for phenol, it is 65 DEG C when column temperature condition setting is initial, 200 DEG C is warming up to 3 DEG C/min speed, then with 10
DEG C/min speed is warming up to 260 DEG C, keeps 6min；For hydroquinones, 50 DEG C when column temperature condition setting is initial, with 8 DEG C/
Min speed is warming up to 220 DEG C, then is warming up to 270 DEG C with 15 DEG C/min speed, keeps 6min；
Step 3-1.2：
Using C18 chromatographic columns (250mm × 4.6mm × 5 μm), setting sample size is 10 μ L, and column flow is 1mL/min, and column temperature is
25 DEG C, the mobile phase acquisition testing wavelength for building raw material is 190nm~400nm 3D data, and wavelength separated degree is 1.2nm.With
271.0nm (phenol) and 289.0nm (hydroquinones) is definite value wavelength, so as to collect chromatogram, chromatogram is returned with area
One, which changes method, calculates acquisition Reinheitszahl；
Wherein, for phenol, flowing phase composition is the pure water of 30% methanol+70%；For hydroquinones, flowing phase composition is 70%
The pure water of methanol+30%；
Step 3-1.3：
(1) residual solvent degree is determined：
It is residual with Static Headspace method sample introduction, gas chromatography separation and fid detector method detection assay successively for testing sample
The degree of solvent is stayed, the condition determination of wherein each process is as follows；
Static Headspace sampling system condition determination is：80 DEG C of equilibrium temperature, 90 DEG C of quantitative loop temperature, 110 DEG C of line of transference temperature, balance
Time 30min, pressing time 2min；
Gas chromatography condition determination is：Using Agilent DB-624 chromatographic columns, 30m × 0.32mm × 0.50 μm, carrier gas stream
Fast 1mL/min, split ratio 10:1,200 DEG C of injector temperature originates 40 DEG C of column temperature, 15min is kept, with 10 DEG C/min program liters
Temperature keeps 10min to 150 DEG C；
Fid detector condition determination is：250 DEG C of temperature；Fid detector being detected to, the chromatogram obtained calculates residual with external standard method
Stay the concentration value of solvent；
(2) moisture percentage assay：For testing sample, the percentage for obtaining moisture is determined with karl Fischer coulomb meter
Content, condition determination is：It is 20 DEG C to detect environment temperature, and humidity is 40%, and polarizing electrode is DM143-5C, the μ of polarization current 5.0
A, instruction unit is voltage (mV), and speed of agitator 45% controls terminal for 100.0mV；The electric current of electrolysis electrode is automatic termination,
Termination type terminates for drift is relative, and drift value is 3.0 μ g/min, and time range is 0~3600s；
(3) percent ash assay：For testing sample, the concentration value for obtaining ash content is determined with thermogravimetric analyzer, is surveyed
Fixed condition is：Using Al2O3Crucible, 650 DEG C are warming up in 25 DEG C of speed with 10 DEG C/min of initial temperature；Record in thermal decomposition process
Mass change, obtain thermogravimetric curve, according to thermogravimetric curve analyze export ash content concentration value；
Step 3-1.4：
I'GC=(100%-Imoi-Isolv-Iash)×IGC
I'HPLC=(100%-Imoi-Isolv-Iash)×IHPLC
In formula, I'GCAnd I'HPLCRespectively gas-chromatography (GC) method and the corresponding amendment purity of high performance liquid chromatography (HPLC) method
Value, IGCAnd IHPLCThe respectively initial purity value of gas-chromatography (GC) method acquisition corresponding with high performance liquid chromatography (HPLC) method,
Imoi、IsolvAnd IashThe concentration value of moisture, dissolvent residual and ash content is represented respectively.
7. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 5 and hydroquinones standard substance
Method, it is characterised in that：
The step 3-2 is specially：Use 40 μ L standard aluminums crucibles of sky for reference, sample weighting amount is 3.24~6.80mg, then is adopted
With three ladders, progressively heating mode is operated, and then obtains Reinheitszahl using purity analysis software Pro teus Analysis
IDSC, and carry out repeatedly determining two groups of purity Value Datas of acquisition.
For phenol, initial temperature is 0 DEG C, is warming up to 20 DEG C with 5 DEG C/min speed, then be warming up to 1 DEG C/min speed
60℃.The temperature-rise period of phenol is
For hydroquinones, initial temperature is 0 DEG C, and 155 DEG C are warming up to 20 DEG C/min speed, then with 10 DEG C/min speed
It is warming up to 190 DEG C.The temperature-rise period of hydroquinones is
8. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 1 and hydroquinones standard substance
Method, it is characterised in that：The step 3-3 is particularly directed to same testing sample, the three groups of purity that will be measured with three kinds of methods
Value Data is handled successively in the following ways：
3-3.1：(it is repeatedly to determine the Reinheitszahl I' obtained for three groups of purity Value DatasGC, I'HPLCAnd IDSC), first transport respectively
Normal distribution inspection is carried out with coefficient of kurtosis method and coefficient of skew method, then outlier is carried out with Grabbs methods and Dixon methods
Examine and reject dubious value；
3-3.2：(i.e. I' between every two groups of Reinheitszahls of three groups of purity Value DatasGCWith I'HPLCBetween, I'HPLCWith IDSCBetween,
I'GCWith IDSCBetween) equally accurate that carries out average value with t methods of inspection examines, with F methods of inspection carry out standard deviation etc.
Accuracy test；
3-3.3：According to the equally accurate result of average value and standard deviation, averaged as raw material final Reinheitszahl：
If the purity Value Data that step 3-3.1 retains meets the equally accurate of average value and standard deviation simultaneously, three groups of purity are taken
The arithmetic mean of instantaneous value of Value Data；
If the purity Value Data that step 3-3.1 retains meets the unequal accuracy of average value and standard deviation when different, three groups are taken
The weighted average of purity Value Data.
9. the Reinheitszahl and the measure side of uncertainty of a kind of phenol according to claim 1 and hydroquinones standard substance
Method, it is characterised in that：It is specially after packing in the step 4：
4-1：Uniformity testing
Respectively from 200 bottles of packing samples according to end to end, middle numbering randomly select 10 bottles of samples, be configured to need testing solution,
Vibration, Reinheitszahl, every bottle of sample parallel determination 3 times are determined according to HPLC methods；Again using one-way analysis of variance method to determining
As a result statistical analysis is carried out, F statistical values are calculated, acquisition F critical values of tabling look-up, by comparing F statistical values and F critical values, are examined and divided
Fill the uniformity of sample；If F statistical values are less than F critical values, sample is uniform；If F statistical values are more than or equal to F critical values, sample
Product are uneven；
F statistical value calculations are as follows：
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In formula, SinterAnd SintraRespectively represent bottle between and bottle internal variance, νinterAnd νintraIt is free between expression bottle and in bottle respectively
Degree；
4-2：Stability test, is divided into short-term stability and long-time stability
4-2.1 short-term stability
Several bottles are randomly selected from packing sample, is individually placed in 4 DEG C, 20 DEG C and 50 DEG C environment, respectively to the 1st day, the 2nd day,
After each 1 bottle of taking-up in 5th day and the 8th day, need testing solution is configured to, is vibrated, Reinheitszahl is determined according to HPLC methods, every bottle of sample is put down
Row is determined 3 times, is averaged；The Reinheitszahl measured again using the packing sample being placed in 4 DEG C of environment is standard, and table look-up acquisition t
Critical value, calculates t statistical values ttest, short-term stability is examined by comparing t statistical values and t critical values：If t statistical values are less than t
Critical value, then sample short-term stability；If t statistical values are more than or equal to t critical values, sample short-term instability；
T statistical values ttestCalculation formula is as follows：
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In formula, x0And s0The purity average value and purity rubric that the packing sample that expression is placed in 4 DEG C of refrigerators respectively is measured are inclined
Difference,Represent to be placed on Reinheitszahl and standard deviation that the packing sample under each different temperatures environment is measured respectively with s, n is represented
The number of times of parallel determination；
4-2.2 long-time stability
Packing sample is stored in 20 DEG C of environment, the STABILITY MONITORING of 12 months is carried out using HPLC methods (see step 3-1.2),
According to thin principle access time node after first close, each timing node chooses 1 sample, each sample parallel determination 3 times, takes
Average value；Then in the case where potential kinetics mechanism is unknown, linear fit is carried out using linear model, the time is represented with x,
The sample purity value of some timing node is represented with y, fitting is in alignment, utilizes the conspicuousness judgement sample of the straight slope
Stability.
10. the Reinheitszahl and the measure of uncertainty of a kind of phenol according to claim 1 and hydroquinones standard substance
Method, it is characterised in that：The step 5 is to calculate to obtain overall uncertainty in the following ways：
5-1：First GC methods are obtained using following computational methods and HPLC methods determine uncertainty caused by Reinheitszahl：
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<mi>P</mi>
<mi>L</mi>
<mi>C</mi>
</mrow>
<mn>2</mn>
</msubsup>
<mo>+</mo>
<msup>
<mrow>
<mo>(</mo>
<msub>
<mi>I</mi>
<mrow>
<mi>G</mi>
<mi>C</mi>
<mo>-</mo>
<mi>H</mi>
<mi>P</mi>
<mi>L</mi>
<mi>C</mi>
</mrow>
</msub>
<mo>)</mo>
</mrow>
<mn>2</mn>
</msup>
<mrow>
<mo>(</mo>
<mrow>
<msubsup>
<mi>u</mi>
<mrow>
<mi>m</mi>
<mi>o</mi>
<mi>i</mi>
</mrow>
<mn>2</mn>
</msubsup>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mrow>
<mi>s</mi>
<mi>o</mi>
<mi>l</mi>
<mi>v</mi>
</mrow>
<mn>2</mn>
</msubsup>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mrow>
<mi>a</mi>
<mi>s</mi>
<mi>h</mi>
</mrow>
<mn>2</mn>
</msubsup>
</mrow>
<mo>)</mo>
</mrow>
</mrow>
</mtd>
</mtr>
</mtable>
</mfenced>
In formula, uGC-HPLCRepresent to obtain IGCAnd IHPLCCaused Composite Seismogram, WithPoint
Biao Shi not first function f1To IGC-HPLC, Imoi, Isolv, IashAsk partial derivative, umoi、usolvAnd uashRepresent that moisture, solvent are residual respectively
Stay and uncertainty caused by ash determination, first function f1It is expressed as f1(IGC-HPLC,Imoi,Isolv,Iash)=(100%-
Imoi-Isolv-Iash)×IGC-HPLC；uGC-HPLCCalculation be：uGCAnd uHPLCRepresent respectively
Obtain IGCAnd IHPLCCaused partial uncertainty；umoi、usolvAnd uashRespectively with moisture, dissolvent residual and the weight of ash determination
Renaturation meter；
5-2：DSC methods are calculated using below equation again and determine uncertainty u caused by ReinheitszahlDSC：
<mrow>
<msub>
<mi>u</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
</mrow>
</msub>
<mo>=</mo>
<msqrt>
<mrow>
<msubsup>
<mi>u</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
<mo>-</mo>
<mi>B</mi>
</mrow>
<mn>2</mn>
</msubsup>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
<mo>-</mo>
<mi>A</mi>
</mrow>
<mn>2</mn>
</msubsup>
</mrow>
</msqrt>
</mrow>
Wherein, uDSC-AAnd uDSC-BRepresent the standard uncertainty of type A evaluation and type B evaluation in DSC methods measure, uDSC-AIt is to pass through
The repeatability of measurement DSC methods, which is calculated, to be obtained；
uDSC-BCalculation formula it is as follows：
<mfenced open = "" close = "">
<mtable>
<mtr>
<mtd>
<mrow>
<msubsup>
<mi>u</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
<mo>-</mo>
<mi>B</mi>
</mrow>
<mn>2</mn>
</msubsup>
<mo>=</mo>
<msup>
<mrow>
<mo>(</mo>
<mrow>
<mfrac>
<mrow>
<mo>&part;</mo>
<msub>
<mi>f</mi>
<mn>2</mn>
</msub>
</mrow>
<mrow>
<mo>&part;</mo>
<mi>m</mi>
</mrow>
</mfrac>
<msub>
<mi>u</mi>
<mi>m</mi>
</msub>
</mrow>
<mo>)</mo>
</mrow>
<mn>2</mn>
</msup>
<mo>+</mo>
<msup>
<mrow>
<mo>(</mo>
<mrow>
<mfrac>
<mrow>
<mo>&part;</mo>
<msub>
<mi>f</mi>
<mn>2</mn>
</msub>
</mrow>
<mrow>
<mo>&part;</mo>
<mi>Q</mi>
</mrow>
</mfrac>
<msub>
<mi>u</mi>
<mi>Q</mi>
</msub>
</mrow>
<mo>)</mo>
</mrow>
<mn>2</mn>
</msup>
<mo>+</mo>
<msup>
<mrow>
<mo>&lsqb;</mo>
<mrow>
<mrow>
<mo>(</mo>
<mrow>
<mfrac>
<mrow>
<mo>&part;</mo>
<msub>
<mi>f</mi>
<mn>2</mn>
</msub>
</mrow>
<mrow>
<mo>&part;</mo>
<msub>
<mi>T</mi>
<mn>0</mn>
</msub>
</mrow>
</mfrac>
<mo>+</mo>
<mfrac>
<mrow>
<mo>&part;</mo>
<msub>
<mi>f</mi>
<mn>2</mn>
</msub>
</mrow>
<mrow>
<mo>&part;</mo>
<msub>
<mi>T</mi>
<mi>m</mi>
</msub>
</mrow>
</mfrac>
</mrow>
<mo>)</mo>
</mrow>
<msub>
<mi>u</mi>
<mi>T</mi>
</msub>
</mrow>
<mo>&rsqb;</mo>
</mrow>
<mn>2</mn>
</msup>
</mrow>
</mtd>
</mtr>
<mtr>
<mtd>
<mrow>
<mo>=</mo>
<msup>
<mrow>
<mo>(</mo>
<mrow>
<msub>
<mi>c</mi>
<mn>1</mn>
</msub>
<msub>
<mi>u</mi>
<mi>m</mi>
</msub>
</mrow>
<mo>)</mo>
</mrow>
<mn>2</mn>
</msup>
<mo>+</mo>
<msup>
<mrow>
<mo>(</mo>
<mrow>
<msub>
<mi>c</mi>
<mn>2</mn>
</msub>
<msub>
<mi>u</mi>
<mi>Q</mi>
</msub>
</mrow>
<mo>)</mo>
</mrow>
<mn>2</mn>
</msup>
<mo>+</mo>
<msup>
<mrow>
<mo>(</mo>
<mrow>
<msub>
<mi>c</mi>
<mn>3</mn>
</msub>
<msub>
<mi>u</mi>
<mi>T</mi>
</msub>
</mrow>
<mo>)</mo>
</mrow>
<mn>2</mn>
</msup>
<mo>=</mo>
<msubsup>
<mi>u</mi>
<mn>1</mn>
<mn>2</mn>
</msubsup>
<mrow>
<mo>(</mo>
<msub>
<mi>I</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
</mrow>
</msub>
<mo>)</mo>
</mrow>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mn>2</mn>
<mn>2</mn>
</msubsup>
<mrow>
<mo>(</mo>
<msub>
<mi>I</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
</mrow>
</msub>
<mo>)</mo>
</mrow>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mn>3</mn>
<mn>2</mn>
</msubsup>
<mrow>
<mo>(</mo>
<msub>
<mi>I</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
</mrow>
</msub>
<mo>)</mo>
</mrow>
</mrow>
</mtd>
</mtr>
</mtable>
</mfenced>
4
Wherein, um, uQ, uTRespectively the weighing error of balance, the calorimetry error of instrument, the temperature error of instrument these three
The standard uncertainty of mutual incoherent input quantity,Second function f is represented respectively2To m,
Q、T0And TmAsk partial derivative, c1, c2And c3The calculated value of quality, heat and temperature is represented respectively；
Second function f2It is expressed as：
<mrow>
<msub>
<mi>f</mi>
<mn>2</mn>
</msub>
<mrow>
<mo>(</mo>
<mi>Q</mi>
<mo>,</mo>
<mi>m</mi>
<mo>,</mo>
<msub>
<mi>T</mi>
<mn>0</mn>
</msub>
<mo>,</mo>
<msub>
<mi>T</mi>
<mi>m</mi>
</msub>
<mo>)</mo>
</mrow>
<mo>=</mo>
<mrow>
<mo>(</mo>
<mn>1</mn>
<mo>-</mo>
<mfrac>
<mrow>
<mi>Q</mi>
<mi>M</mi>
<mrow>
<mo>(</mo>
<msub>
<mi>T</mi>
<mn>0</mn>
</msub>
<mo>-</mo>
<msub>
<mi>T</mi>
<mi>m</mi>
</msub>
<mo>)</mo>
</mrow>
</mrow>
<mrow>
<msubsup>
<mi>mRT</mi>
<mn>0</mn>
<mn>2</mn>
</msubsup>
</mrow>
</mfrac>
<mo>)</mo>
</mrow>
<mo>&times;</mo>
<mn>100</mn>
<mi>%</mi>
</mrow>
In formula, T0And TmThe melting temperature of pure sample product and actual sample is represented respectively, and R is gas constant, and Q is the heat that sample absorbs
Amount, m is the quality of sample, and M is the molal weight of sample；
5-3：Calculate a point uncertainty
Calculated according to the one-way analysis of variance result that uniformity testing is obtained using below equation caused by obtaining uniformity not
Degree of certainty uH：
<mrow>
<msub>
<mi>u</mi>
<mi>H</mi>
</msub>
<mo>=</mo>
<msqrt>
<mrow>
<mo>(</mo>
<msub>
<mi>S</mi>
<mrow>
<mi>int</mi>
<mi>e</mi>
<mi>r</mi>
</mrow>
</msub>
<mo>-</mo>
<msub>
<mi>S</mi>
<mrow>
<mi>int</mi>
<mi>r</mi>
<mi>a</mi>
</mrow>
</msub>
<mo>)</mo>
<mo>/</mo>
<mn>3</mn>
</mrow>
</msqrt>
</mrow>
The standard deviation for examining obtained fitting a straight line slope according to long-time stability is multiplied by the STABILITY MONITORING time, using following
Formula calculates and obtains uncertainty u caused by stabilitys：
uS=s (b1)·t
5-4：Calculate overall uncertainty
Overall uncertainty calculation formula is expressed as below：
<mrow>
<msub>
<mi>u</mi>
<mi>C</mi>
</msub>
<mo>=</mo>
<msqrt>
<mrow>
<mfrac>
<mn>1</mn>
<mn>2</mn>
</mfrac>
<mrow>
<mo>(</mo>
<msubsup>
<mi>u</mi>
<mrow>
<mi>G</mi>
<mi>C</mi>
<mo>-</mo>
<mi>H</mi>
<mi>P</mi>
<mi>L</mi>
<mi>C</mi>
</mrow>
<mrow>
<mo>&prime;</mo>
<mn>2</mn>
</mrow>
</msubsup>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mrow>
<mi>D</mi>
<mi>S</mi>
<mi>C</mi>
</mrow>
<mn>2</mn>
</msubsup>
<mo>)</mo>
</mrow>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mi>H</mi>
<mn>2</mn>
</msubsup>
<mo>+</mo>
<msubsup>
<mi>u</mi>
<mi>S</mi>
<mn>2</mn>
</msubsup>
</mrow>
</msqrt>
</mrow>
GC methods, HPLC methods and DSC methods obtained by step 5-1 and step 5-2 are determined into uncertainty caused by purity, and step 5-
Uncertainty caused by 3 gained uniformities and stability substitutes into above formula, and calculating obtains overall uncertainty.
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| CN108535069A (en) * | 2018-04-20 | 2018-09-14 | 中国农业科学院农业质量标准与检测技术研究所 | A kind of nobiletin purity rubric substance and the preparation method and application thereof |
| CN108693267A (en) * | 2018-05-18 | 2018-10-23 | 中国烟草总公司郑州烟草研究院 | 4- methyl benzophenone purity rubric substances and preparation method thereof |
| CN108931591A (en) * | 2018-05-18 | 2018-12-04 | 中国烟草总公司郑州烟草研究院 | Photoinitiator mixed solution standard substance and preparation method thereof |
| CN109521134A (en) * | 2018-11-24 | 2019-03-26 | 上海化工研究院有限公司 | The deuterium-labeled own ester standard substance of phthalic acid two (2- ethyl) measures and application |
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| CN108693267B (en) * | 2018-05-18 | 2020-12-08 | 中国烟草总公司郑州烟草研究院 | 4-methylbenzophenone purity standard substance and preparation method thereof |
| CN108693267A (en) * | 2018-05-18 | 2018-10-23 | 中国烟草总公司郑州烟草研究院 | 4- methyl benzophenone purity rubric substances and preparation method thereof |
| CN108931591A (en) * | 2018-05-18 | 2018-12-04 | 中国烟草总公司郑州烟草研究院 | Photoinitiator mixed solution standard substance and preparation method thereof |
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| CN110824045A (en) * | 2019-11-08 | 2020-02-21 | 浙江省计量科学研究院 | Method for developing phthalate standard substance in soil |
| CN111198200A (en) * | 2020-01-14 | 2020-05-26 | 广东省计量科学研究院（华南国家计量测试中心） | Nickel Curie point standard substance and preparation method thereof |
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| CN112649324A (en) * | 2020-12-30 | 2021-04-13 | 上海电缆研究所有限公司 | Analysis method for evaluating consistency of non-metallic material for nuclear power station cable |
| CN113009011A (en) * | 2021-02-19 | 2021-06-22 | 广东省计量科学研究院（华南国家计量测试中心） | 4,4' -dibromodiphenyl ether purity standard substance and preparation method thereof |
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