CN113009011A - 4,4' -dibromodiphenyl ether purity standard substance and preparation method thereof - Google Patents

4,4' -dibromodiphenyl ether purity standard substance and preparation method thereof Download PDF

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CN113009011A
CN113009011A CN202110189467.5A CN202110189467A CN113009011A CN 113009011 A CN113009011 A CN 113009011A CN 202110189467 A CN202110189467 A CN 202110189467A CN 113009011 A CN113009011 A CN 113009011A
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dibromodiphenyl ether
purity
standard substance
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dibromodiphenyl
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陈玲
许俊斌
罗思婷
廖泽荣
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Guangdong Provincial Institute Of Metrology (south China National Centre Of Metrology)
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Abstract

The invention discloses a preparation method of a 4,4' -dibromodiphenyl ether purity standard substance, which comprises the following steps: respectively carrying out qualitative analysis on the 4,4' -dibromodiphenyl ether by gas chromatography-mass spectrometry and nuclear magnetic resonance; after the raw material substances are determined by qualitative analysis, carrying out primary uniformity detection on the 4,4 '-dibromodiphenyl ether by adopting a liquid chromatography, and screening out samples with uniform purity as 4,4' -dibromodiphenyl ether purity standard substance candidates; and (3) carrying out uniformity inspection, stability inspection and fixed value and uncertainty analysis on the 4,4 '-dibromodiphenyl ether purity standard substance candidate according to the metrological requirements, wherein if the uniformity, the stability and the uncertainty meet the requirements, the fixed value is accurate and stable, and the 4,4' -dibromodiphenyl ether purity standard substance candidate meets the metrological characteristics. The 4,4' -dibromodiphenyl ether purity standard substance developed by the invention is mainly used as a standard for quantity value transmission, meets the requirements of the current research and detection, and is used for the related research of brominated flame retardants.

Description

4,4' -dibromodiphenyl ether purity standard substance and preparation method thereof
Technical Field
The invention belongs to the technical field of metering, relates to an organic matter standard substance, and particularly relates to a 4,4' -dibromodiphenyl ether purity standard substance and a preparation method thereof.
Background
In the prior art, methods such as gas chromatography, liquid chromatography, gas chromatography-mass spectrometry and the like are generally adopted for detecting polybrominated diphenyl ether, however, the sensitivity of various methods is inconsistent, so that the difference of the analysis results of the medicines is large, and therefore, uniform standard substances are required to realize uniform quantity values. 4,4 '-dibromodiphenyl ether is used as one of polybrominated diphenyl ethers, and the research on the purity standard thereof realizes the traceability of the quantity value, so that the detection result has comparability and uniformity and has great practical significance, thereby being very necessary to provide a research method of the purity standard of the 4,4' -dibromodiphenyl ether.
Disclosure of Invention
The invention aims to provide a 4,4' -dibromodiphenyl ether purity standard substance and a preparation method thereof, which aim to solve the problem that the detection method in the prior art cannot meet the requirement of fixed value.
According to one aspect of the invention, the preparation method of the standard substance of the purity of 4,4' -dibromodiphenyl ether is provided, which comprises the following steps:
selecting 4,4 '-dibromodiphenyl ether with the purity of more than 99 percent as a purity sample, and respectively adopting gas chromatography-mass spectrometry and nuclear magnetic resonance to carry out qualitative analysis on the 4,4' -dibromodiphenyl ether purity sample;
after a purity sample substance is determined by qualitative analysis, carrying out uniformity primary detection on the 4,4' -dibromodiphenyl ether by adopting a liquid chromatography, screening out the 4,4' -dibromodiphenyl ether with uniform purity, wherein a sample passing the uniformity primary detection is the 4,4' -dibromodiphenyl ether which is a purity standard substance candidate;
and (3) carrying out uniformity inspection, stability inspection and fixed value and uncertainty analysis on the 4,4 '-dibromodiphenyl ether purity standard substance candidate according to the metrological requirements, wherein if the uniformity, the stability and the uncertainty meet the requirements, the fixed value is accurate and stable, and the 4,4' -dibromodiphenyl ether purity standard substance candidate meets the metrological characteristics.
In some embodiments, when gas chromatography is performed using gas chromatography-mass spectrometry, the steps are as follows: accurately weighing 50.2mg of 4,4 '-dibromodiphenyl ether, and metering the volume to a 50mL brown volumetric flask by using methanol to obtain a solution of 4,4' -dibromodiphenyl ether in methanol with the concentration of 1.04 mg/mL;
the 4,4' -dibromodiphenyl ether solution in the prepared methanol is analyzed by gas chromatography-mass spectrometry under the following conditions: the sample inlet temperature is 250 ℃, the connection port temperature is 280 ℃, the ion source temperature is 230 ℃, the constant flow mode is 1mL/min, the sample injection amount is 1 muL, the split ratio is 1:10, the scanning range is 50-550, the solvent delay is 3min, the chromatographic column HP-5MS (30m multiplied by 0.32mm multiplied by 0.25um) has the column temperature of 60 ℃, the temperature rise rate is increased to 200 ℃ at the speed of 5 ℃/min, and the temperature is kept for 22 min.
In some embodiments, the preliminary homogeneity detection step using liquid chromatography is as follows: taking 50.0mg of 4,4 '-dibromodiphenyl ether from the upper part, the middle part and the lower part of a sample bottle filled with the 4,4' -dibromodiphenyl ether respectively, dissolving the 4,4 '-dibromodiphenyl ether in methanol to a volumetric flask with the volume being 25mL by using methanol, and preparing to obtain a solution of the 4,4' -dibromodiphenyl ether in the methanol with the concentration of 2.0 mg/mL;
a C18 column is adopted, methanol-water with the volume ratio of 90 percent to 10 percent is taken as a mobile phase, the detection wavelength is 230nm, and the purity of the 4,4' -dibromodiphenyl ether is calculated according to the chromatographic peak area.
In some embodiments, the homogeneity test procedure performed on a 4,4' -dibromodiphenyl ether purity standard candidate is as follows: randomly extracting 11 bottles of samples from sample bottles filled with 4,4' -dibromodiphenyl ether purity standard substance candidates according to serial numbers of head, tail and middle; weighing 50mg of each bottle of sample, metering the volume to a 50mL volumetric flask by using methanol respectively, preparing a solution of 4,4' -dibromodiphenyl ether in the methanol of 1.0mg/mL, and measuring the purity value of each sample by using a gas chromatograph for 3 times in parallel, wherein the purity value of 3 times of measurement is used as the result of uniformity evaluation.
In some embodiments, the gas chromatography conditions used to measure the purity value of the measurement by the gas chromatograph are: the sample inlet temperature is 250 ℃, the detector temperature is 250 ℃, the constant flow is 6.5mL/min, the sample injection amount is 1 mu L, the split ratio is 1:10, chromatographic column HP-5, column temperature 100 deg.C, keeping for 0.5min, heating to 250 deg.C at a rate of 15 deg.C/min, and keeping for 5 min.
In some embodiments, the stability test comprises a long term stability test and a short term stability test; and (3) long-term stability checking: measuring the 4,4 '-dibromodiphenyl ether purity standard substance solution by adopting a gas chromatograph at different time intervals, fitting a straight line by using x as time and y as the purity of the 4,4' -dibromodiphenyl ether purity standard substance, and judging whether the long-term stability exists according to the slope of the straight line; short-term stability checking step: randomly extracting 6 sample bottles filled with 4,4' -dibromodiphenyl ether purity standard substance candidates, placing at (60 +/-2) DEG C for storage for one week, and measuring the purity; and (4) performing regression analysis according to the purity measurement result to judge whether the short-term stability reaches the standard.
In some embodiments, the determination is performed by mass balance method and differential scanning calorimetry, and the average of the results of the mass balance method and differential scanning calorimetry is taken as the determination.
In some embodiments, the specific steps for mass balance law value are as follows: determining organic impurities by gas chromatography and high performance liquid chromatography, determining water content by a Kaschinger moisture analyzer, determining inorganic impurity content by a firing method, performing solvent residue analysis, and determining a value by mass balance;
the specific steps of the differential scanning calorimetry method for setting the value are as follows: accurately weighing 3.000mg of a 4,4' -dibromodiphenyl ether purity standard substance candidate, accurately weighing the candidate to 0.001mg, flatly paving the candidate at the bottom of an aluminum crucible, sealing the candidate, placing the candidate in a DSC instrument, and taking a 40 mu L standard aluminum empty crucible as a reference crucible; furnace body atmosphere: static air; the purge gas is N 240 mL/min; protective gas: nitrogen gas, 60 mL/min; stabilizing the sample at-40 deg.C for 30min, and heating to 40 deg.C at a heating rate of 0.5K/min; taking 11 bottles of samples which are randomly extracted, testing twice in each bottle, and analyzing and valuing the purity result.
In some embodiments, the uncertainty includes 4,4' -dibromodiphenyl ether-valued experimental-induced uncertainty, 4' -dibromodiphenyl ether-unevenly-generated uncertainty, and 4,4' -dibromodiphenyl ether-unstably-generated uncertainty.
According to another object of the invention, the 4,4' -dibromodiphenyl ether purity standard substance obtained by the preparation method is provided. The 4,4' -dibromodiphenyl ether purity standard substance developed by the invention is mainly used as a standard for quantity value transmission, meets the requirements of the current research and detection, and is used for the related research of brominated flame retardants.
Drawings
FIG. 1 is a total ion flow diagram of 4,4' -dibromodiphenyl ether;
FIG. 2 is a mass spectrum fragment peak of a 4,4' -dibromodiphenyl ether sample;
FIG. 3 is a standard spectrum of 4,4' -dibromodiphenyl ether mass spectrum;
FIG. 4-5 shows the H spectrum and C spectrum of 4,4' -dibromodiphenyl ether nuclear magnetic resonance;
FIG. 6 is a gas chromatogram for uniformity test of 4,4' -dibromodiphenyl ether;
FIG. 7 is a long-term stability trend chart of 4,4' -dibromodiphenyl ether purity standard substance candidate;
FIG. 8 is a graph showing the stability trend of 4,4' -dibromodiphenyl ether at 60 ℃;
FIG. 9 is a 3D wavelength scan of 4,4' -dibromodiphenyl ether;
FIGS. 10 to 11 are high performance liquid chromatograms (2.0mg/mL, sample size 2. mu.L) of 4,4' -dibromodiphenyl ether;
FIG. 12 is a high performance liquid chromatogram of methanol;
FIGS. 13 to 17 are HPLC charts of 4,4' -dibromodiphenyl ether in methanol at concentrations of 1mg/L, 10mg/L, 100mg/L, and 2200mg/L, respectively;
FIG. 18 is a high performance liquid chromatogram of 4,4' -dibromo diphenyl ether;
FIGS. 19 to 20 are gas chromatograms of 4,4' -dibromo diphenyl ether;
FIG. 21 is a gas chromatogram of methanol;
FIGS. 22 to 26 are GC graphs of 4,4' -dibromodiphenyl ether in methanol at concentrations of 1mg/L, 10mg/L, 100mg/L, 1000mg/L, and 2200mg/L, respectively;
FIG. 27 is a total ion flow diagram of 4,4' -dibromodiphenyl ether with n-hexane as the solvent;
FIG. 28 is a diagram showing the total ion flow of 4,4' -dibromodiphenyl ether with dichloromethane as the solvent;
FIGS. 29 to 30 are a DSC chart, a melting thermogram, and a melting thermogram of phenyl salicylate;
FIGS. 31 to 34 are DSC images of 4,4' -dibromodiphenyl ether at temperature rising rates of 0.3K/min, 0.5K/min, 0.7K/min and 1K/min, respectively;
FIGS. 35 to 38 are the results of analyzing the purity of 4,4' -dibromodiphenyl ether at a temperature rise rate of 0.3K/min, 0.5K/min, 0.7K/min, and 1K/min, respectively.
Detailed Description
The present invention will be described in further detail with reference to the accompanying drawings. Wherein, the purity sample 4,4' -dibromodiphenyl ether used in the embodiment is from SIGMA-ALDRICH, CAS2050-47-7, nominal purity (GC) is 99.2%, 5 bottles of samples are purchased, 100 g/bottle are purchased, and the samples are uniformly ground and stored in a dryer; in the experimental process, methanol and acetonitrile are both chromatographic grade reagents (Merck), and the experimental water is ultrapure water.
Equipment for standard substance preparation: a 250mL class a volumetric flask; electronic balances (CPA225D, d 0.1mg) (sartorius, germany) were all certified; packaging containers: 5mL brown sample bottle.
The apparatus used was as follows: gas chromatograph (7890B, Agilent Technologies), equipped with FID detector; liquid chromatography (e2695, Waters), diode-array detector (2998, Waters), C18 chromatography column (250mm × 4.6mm, i.d.,5 μm); differential scanning calorimeter, DSC 214Polyma, NETZSCH; ka's moisture meter (C20, METTLER TOLLEDO); inductively coupled plasma mass spectrometers (7900, Agilent technologies); mass comparator, CC50, Sartorius, d ═ 0.001 mg. The instruments and the used glassware are qualified by the verification or calibration of the Guangdong province metrological scientific research institute or the equivalent legal metrological technical institution.
In order to develop a standard substance of purity of 4,4' -dibromodiphenyl ether, the following operations were carried out in this example:
first, qualitative analysis of raw material
Firstly, qualitative analysis is carried out by gas chromatography-mass spectrometry: accurately weighing 50.2mg of a 4,4 '-dibromodiphenyl ether purity sample, and metering the volume to a 50mL brown volumetric flask by using methanol to obtain a 4,4' -dibromodiphenyl ether solution in the methanol with the concentration of 1.04 mg/mL; and (3) carrying out gas chromatography-mass spectrometry analysis on the prepared 4,4' -dibromodiphenyl ether solution in the methanol, wherein the gas chromatography-mass spectrometry conditions are as follows: the sample inlet temperature is 250 ℃, the connection port temperature is 280 ℃, the ion source temperature is 230 ℃, the constant flow mode is 1mL/min, the sample injection amount is 1 muL, the split ratio is 1:10, the scanning range is 50-550, the solvent delay is 3min, the chromatographic column HP-5MS is adopted, the column temperature is 60 ℃, the temperature is increased to 200 ℃ at the speed of 5 ℃/min, and the retention time is 22 min.
The total ions obtained are shown in figure 1, the mass spectrum fragment peaks and the detection results are shown in figure 2, and it can be seen that the sample fragment ions are consistent with the standard fragment ion spectrogram (figure 3), and the main fragment ions have the following fragmentation routes:
Figure BDA0002944797490000041
the gas quality analysis result shows that the sample is 4,4' -dibromodiphenyl ether, and simultaneously, the impurity is searched to be 4-bromodiphenyl ether.
Then, qualitative analysis was performed using nuclear magnetic resonance apparatus (JOEL-ECX500, japan electronics, 500MHz), and a nuclear magnetic resonance H spectrum was obtained as shown in fig. 4, in which 4,4' -dibromodiphenyl ether was bonded to the molecular structure, and the chemical shift of H atom was as follows:
Figure BDA0002944797490000042
1H NMR(500MHz,DMSO-D6)δ7.51-7.48(m,4H,J＝2.25；3,5,3’,5’-4H),6.95-6.91(m,4H,J＝2.25；2,6,2’,6’-4H).
the obtained nuclear magnetic resonance carbon spectrum is shown in figure 5, the molecular structure of the 4,4' -dibromodiphenyl ether is combined, and the chemical shift attribution of C atoms is as follows:
Figure BDA0002944797490000043
13C NMR(126MHz,DMSO-D6)δ156.13(s,2C；1,1’-2C),133.40(s,4C；3,5,3’,5’-4C),121.37(s,4C；2,6,2’,6’-4C),116.15(s,2C；4,4’-2C).
the sample is 4,4' -dibromodiphenyl ether, which can be obtained from gas analysis and nuclear magnetic qualitative results.
Second, uniformity initial inspection
50.0mg of purity sample 4,4 '-dibromodiphenyl ether is taken from the upper part, the middle part and the lower part of a sample bottle respectively, dissolved in methanol to a volumetric flask with the volume being 25mL, and prepared to obtain a solution of 4,4' -dibromodiphenyl ether in methanol with the concentration of 2.0 mg/mL. And performing initial uniformity detection by using an optimized liquid chromatography detection method.
A C18 column (250mm 4.6mm 5 μm) was used, methanol-water was used as the mobile phase, the volume ratio of methanol to water was 90% to 10%, the detection wavelength was 230nm, and the purities of the upper, middle and lower samples are shown in Table 1.
TABLE 14, 4' -Dibromodiphenyl ether for initial homogeneity test
Figure BDA0002944797490000044
Figure BDA0002944797490000051
And (3) subpackaging the sample into 5mL brown sample bottles, wherein each bottle contains not less than 500mg, sealing, storing at normal temperature, subpackaging 200 bottles at one time, and marking as a purity standard substance candidate bottle.
Third, uniformity detection
The homogeneity of the standard substance is an important measure of the performance of the standard substance and is the basis of the substance for the accurate delivery of the quality value of the standard substance, and the characteristics of the standard substance should be homogeneous, i.e. the characteristics remain unchanged within a certain sub-range. Standard material homogeneity tests are typically performed by randomly taking a number of samples and measuring them using highly accurate test methods.
In the process of developing the 4,4' -dibromodiphenyl ether purity standard substance, the homogeneity of the tested sample is counted by an analysis of variance method. The method judges whether there is a systematic difference between each group of measured values by comparing the variance between groups and the variance within groups, and if the ratio of the two is less than the critical value of the statistical test, the sample is considered to be uniform.
Referring to the technical specification JJF1343-2012 of the standard substance, 11 bottles of standard samples are randomly extracted from the purity standard substance candidates which are divided and numbered according to head-tail and middle numbers. Weighing appropriate 50mg of standard substance candidate in each bottle of purity standard substance candidate, and metering the volume of the standard substance candidate into a 50mL volumetric flask by using methanol to prepare a solution of 4,4' -dibromodiphenyl ether in the methanol of 1.0 mg/mL.
First, the normalcy of the equation is examined. Measured using a gas chromatograph (FID detector), the gas chromatographic conditions were as follows: the sample inlet temperature is 250 ℃, the detector temperature is 250 ℃, the constant flow is 6.5mL/min, the sample injection amount is 1 muL, the split ratio is 1:10, the chromatographic column HP-5 is 30m multiplied by 0.320mm, 0.25m, 19091J-413, the column temperature is 100 ℃, the retention time is 0.5min, the temperature is increased to 250 ℃ at the temperature increase rate of 15 ℃/min, and the retention time is 5 min.
Respectively transferring 0.1mL, 1mL and 10mL of 4,4' -dibromodiphenyl ether solution in methanol with the concentration of 1000mg/L, diluting and fixing the volume to a 100mL volumetric flask; 221.1mg of 4,4' -dibromodiphenyl ether is weighed, the volume is determined to be 100mL volumetric flask by methanol, 4' -dibromodiphenyl ether solution in methanol with the concentration of 2200mg/L is prepared, and the measurement linearity of the 4,4' -dibromodiphenyl ether solution in methanol with each concentration is shown in Table 2.
TABLE 2 Linear relationship of measurement results of 4,4' -dibromodiphenyl ether solution in methanol of different concentrations
Figure BDA0002944797490000052
Next, the method reproducibility was examined. The measurement was conducted 6 times at 1000mg/L, and the measurement reproducibility is shown in Table 3.
TABLE 3 Linear relationship of measurement results of 4,4' -dibromodiphenyl ether solution in methanol of uniform concentration
Figure BDA0002944797490000053
Under these conditions, the gas chromatogram of 4,4' -dibromodiphenyl ether is shown in FIG. 6.
Next, 3 times of the purity value measured for each purity standard substance candidate was determined in parallel, 3 times as a result of the uniformity evaluation, and subjected to analysis of variance. The samples were examined for homogeneity using analysis of variance at 95% confidence probability (ISO guide 35) and the results are shown in tables 4 and 5.
TABLE 44 homogeneity data and results for 4,4' -dibromodiphenyl ether purity standard candidate
Figure BDA0002944797490000054
Figure BDA0002944797490000061
TABLE 54 homogeneity results analysis of variance of 4,4' -dibromodiphenyl ether purity standard substance candidates
Source of difference SS df MS F P-value Fcrit
Between groups 6.95×10-6 10 6.95E-07 1.84 0.112 2.30
In group 8.31E-06 22 3.78E-07
Total of 1.53E-05 32
From the data in the table, one can see:
Figure BDA0002944797490000062
Figure BDA0002944797490000063
F<Fαindicates the absence of samplesThe difference was significant.
As can be seen from the calculation, the statistical quantity F value of the measurement result of the 4, 4-dibromodiphenyl ether purity standard substance candidate is less than the homogeneity test critical value FαThe 4,4' -dibromodiphenyl ether purity standard substance candidate was proved to be homogeneous. The standard deviation produced by the non-uniformity between sample bottles is similar to the standard deviation measured by the method, and the uniformity factor must be taken into account in calculating the total uncertainty.
The statistical method shows that the homogeneity of the 4,4' -dibromodiphenyl ether purity standard substance candidate is good, and the sampling amount in the homogeneity measurement is 50 mg. However, in DSC fixed value, the sampling amount of 4,4' -dibromodiphenyl ether is 3mg, and the fixed value data meets the requirements of standard substance development technical specifications through inspection. Therefore, the minimum sample size of the 4,4' -dibromodiphenyl ether purity standard substance candidate was 3 mg.
Fourthly, stability detection
The stability of the reference substance is a change over time in the characteristic amount of the specified value, and is influenced by physical, chemical, and storage conditions, and includes long-term stability and short-term stability.
For long-term stability, it is necessary to periodically examine it over time with highly accurate analytical methods to determine the relative stability period. The stability of the 4, 4-dibromodiphenyl ether purity standard substance candidate is investigated according to the standard substance technical specification and the principle of tight front and loose back. Stability was measured by gas chromatography (FID detector), and the standard solution was measured at different time intervals and subjected to statistical analysis, and the trend of stability of the 4,4' -dibromodiphenyl ether purity standard substance candidate was shown in FIG. 7, and the results are shown in Table 6.
TABLE 64, 4' -dibromodiphenyl ether purity standard substance candidate stability experimental data and regression analysis results
Figure BDA0002944797490000071
Since no physical/chemical model can truly describe the degradation mechanism of the candidate standard sample, a straight line is used as an empirical model. The data in the table, x represents time and y represents concentration, are fitted to a straight line, and the stability of the sample is judged by evaluating the final regression table. The results of the regression analysis are shown in Table 7.
TABLE 74 regression analysis results of long-term stability experimental data of 4,4' -dibromodiphenyl ether purity standard substance candidates
Coefficients Standard error of t Stat P value The lower limit is 95.0% The upper limit is 95.0%
Intercept 0.9928 0.00033 3046.05 1.09E-22 0.9921 0.9936
XVariable1 2.66E-05 2.85E-05 0.93 0.38 -4.1E-05 9.4E-05
Since no physical/chemical model can truly describe the degradation mechanism of the candidate standard sample, when a straight line is used as an empirical model, x represents time, and y represents the purity of the 4,4' -dibromodiphenyl ether purity standard substance, the slope of the straight line is as follows:
Figure BDA0002944797490000072
in the formula:
Figure BDA0002944797490000073
the intercept is calculated by:
Figure BDA0002944797490000074
the uncertainty of the slope is:
Figure BDA0002944797490000075
the t distribution factor for the degree of freedom f-n-2-7 and p-0.95 (95% confidence level) is equal to 2.36, so
t0.95,n-2·s(b1)＝2.36×2.85×10-5＝6.73×10-5
Due to | b1|＜t0.95,n-2·s(b1) The slope is not significant.
Thus, no instability was observed, indicating that there was no significant trend change in the amount of the 4,4 '-dibromodiphenyl ether purity standard candidate within 24 months, indicating that the storage conditions taken by us effectively ensured the stability of the amount of the 4,4' -dibromodiphenyl ether purity standard candidate.
By short term stability is meant the stability of the standard substance during transport under transport conditions. In order to examine the effect of transport conditions on the stability of the standard substances, 6 bottles of samples were randomly sampled, stored for one week under transport conditions (60. + -.2). degree.C. (dry box), and examined for stability. The stability trend is shown in fig. 8, and the stability data and the analysis results are shown in tables 8 and 9.
TABLE 84, 4' -dibromodiphenyl ether purity standard substance candidate short-term stability experimental data and analysis of variance results
Figure BDA0002944797490000081
TABLE 94 regression analysis of stability test data of 4,4' -dibromodiphenyl ether at 60 deg.C
Coefficients Standard error of tStat P-value The lower limit is 95.0% The upper limit is 95.0%
Intercept 0.9927 0.00026 3834.8 2.77E-14 0.9920 0.9934
XVariable1 -3.5E-06 5.9E-05 -0.059 0.96 -0.0002 0.00016
When x represents time and the purity of the standard substance of the purity of the y-substituted 4,4' -dibromodiphenyl ether is fitted into a straight line, the slope of the straight line is as follows:
Figure BDA0002944797490000082
in the formula:
Figure BDA0002944797490000083
the intercept is calculated by:
Figure BDA0002944797490000084
the uncertainty of the slope is:
Figure BDA0002944797490000085
the t distribution factor for the degree of freedom f-n-2-4 and p-0.95 (95% confidence level) is equal to 2.78, so
t0.95,n-2·s(b1)＝2.78×5.9×10-5＝1.6×10-4
Due to | b1|＜t0.95,n-2·s(b1) The slope is not significant.
Thus, no instability was observed, and the 4,4' -dibromodiphenyl ether purity standard substance candidate was stable at 60 ℃ during examination.
Through long-term stability and short-term stability investigation, the stability of the 4,4' -dibromodiphenyl ether purity standard substance candidate is good within 24 months of the stabilization period, the quantity value is not obviously changed, and the stability of the standard substance is well ensured under the storage condition and the transportation condition.
Fifthly, constant value
The purity of the 4,4' -dibromodiphenyl ether is measured by adopting two fixed value methods of a mass balance method and a differential scanning calorimetry method which have different principles. When the mass balance method is adopted for measurement, organic impurities are determined by gas chromatography and high performance liquid chromatography, the moisture content is determined by a Karschner moisture analyzer, the inorganic impurity content is determined by a firing method, and solvent residue analysis is carried out, specifically as follows:
for the high performance liquid chromatography, 99.6mg of 4,4 '-dibromodiphenyl ether was accurately weighed, and the volume was adjusted to 50mL with methanol to prepare a methanol solution of 4,4' -dibromodiphenyl ether with a concentration of 2.0mg/mL, which was subjected to HPLC-DAD analysis.
Full-wavelength scanning was performed using a C18 column (250mm 4.6mm 5 μm) and methanol-water (90% -10%, v: v) as mobile phases, and the scanning results are shown in fig. 9, where the detection wavelength of 4,4 '-dibromodiphenyl ether was selected to be 230nm, thus obtaining the hplc analysis conditions of 4,4' -dibromodiphenyl ether: detector DAD, C18 chromatographic column, methanol-water (90% -10%, v: v) as mobile phase, detecting wavelength 230nm, flow rate 1.0ml/min, column temperature 30 deg.C. Under these conditions, the chromatograms for purity examination are shown in fig. 10 and fig. 11, and in comparison with the blank chromatogram of methanol (fig. 12), it can be seen that 4,4' -dibromodiphenyl ether contains an impurity component.
The measurement method was examined for linearity. Solutions of 4,4' -dibromodiphenyl ether in methanol of 1mg/L, 10mg/L, 100mg/L, 1000mg/L and 2200mg/L are respectively measured, a high performance liquid chromatogram is shown in figures 13-17, and linearity in the range of 1-2200 mg/L under the conditions is measured. The areas of the different concentration peaks and the linear coefficients are shown in table 10.
TABLE 10 Peak area and Linear coefficient for different concentrations
Figure BDA0002944797490000091
11 samples were randomly taken from the purity standard substance candidate bottle, and prepared into a solution of 4,4' -dibromodiphenyl ether in methanol of 2.0mg/mL, and subjected to high performance liquid chromatography analysis, and the obtained sample impurity analysis is shown in FIG. 18, and the peak area normalization was employed to obtain 11 sample high performance liquid purity values shown in Table 11.
TABLE 114, 4' -Dibromodiphenyl ether high performance liquid chromatography analysis results
Figure BDA0002944797490000092
Normal distribution test is carried out on the fixed value data, and the skewness coefficient A and the kurtosis coefficient B are calculated as follows:
Figure BDA0002944797490000093
Figure BDA0002944797490000094
Figure BDA0002944797490000101
Figure BDA0002944797490000102
Figure BDA0002944797490000103
when P is 0.95 and n is 22, looking up the table D.1 to obtain A1 which is 0.71 and A is less than A1;
the critical interval is 1.82-4.16, and the value B is within the range, so that the data can be accepted as normal distribution.
Examination of outliers in experimental data:
grabbs method, in a set of measured values, if the measured value xiHaving residual error
Figure BDA0002944797490000104
When v isiWhen λ (α, n) s is larger, x isiShould be rejected. In this set of data, the maximum residual is 0.0007, and λ (5%, 22) ═ 2.758, and s ═ 3.7 × 10-4，λ(α，n)s＝2.758×3.7×10-4＝0.0010＞0.0007。
Dixon (Dixon) method: arranging the measurement data from small to large:
X(1)≤X(2)≤···≤X(n-1)≤X(n)
since the number of measurements is 22, r is calculated by the following formula1And rn。
Figure BDA0002944797490000105
If r1＞rnAnd r is1＞f(α，n)Then, X is judged(1)Is an abnormal value; if rn＞r1And r isn＞f(α，n)Then, X is judged(n)Is an abnormal value; if r1And rnAll values are less than f(α，n)Value, then all data is retained.
According to experimental data, the following are calculated: r is1＝0.428，rnLooking up the table to obtain f(α，n)＝0.468。r1And rnAll values are less than f(α，n)The value of this set of data is not anomalous, so all data is retained.
For gas chromatography, a sample is randomly extracted to prepare a solution of 4,4' -dibromodiphenyl ether in methanol of 1000mg/L for gas chromatography analysis, and the temperature programming and the chromatographic conditions are as follows: the sample inlet temperature is 250 ℃, the detector temperature is 250 ℃, the fixed flow rate is 6.5mL/min, the sample feeding amount is 1 muL, the split ratio is 1:10, the chromatographic column HP-5, 30m, 0.320mm, 0.25μm, 19091J-413, the column temperature is 60 ℃, the retention time is 0.5min, the temperature is increased to 100 ℃ at the speed of 5 ℃/min, then is increased to 250 ℃ at the speed of 10 ℃/min, and the retention time is 6.5 min. The gas chromatograms obtained are shown in fig. 19 and 20, and the gas chromatogram of the control sample and methanol blank (fig. 21), and one impurity peak was observed. From the results of gas chromatography and liquid chromatography analysis, both analysis methods can obtain one impurity peak, and the analysis results are consistent.
A survey of the linearity of the measurement method measurement. Solutions of 4,4' -dibromodiphenyl ether in methanol of 1mg/L, 10mg/L, 100mg/L, 1000mg/L and 2200mg/L were measured respectively, gas chromatograms are shown in FIGS. 22-26, linearity in the range of 1-2200 mg/L under the conditions was measured, and chromatographic peak areas and linearity coefficients at different concentrations are shown in Table 12.
TABLE 12 chromatographic peak area and Linear coefficient at different concentrations
Figure BDA0002944797490000106
Figure BDA0002944797490000111
The results of the sample peak area normalized purity analysis are shown in table 13.
TABLE 134, 4' -dibromodiphenyl ether gas chromatography results
Figure BDA0002944797490000112
Normal distribution test is carried out on the fixed value data, and the skewness coefficient A and the kurtosis coefficient B are calculated as follows:
Figure BDA0002944797490000113
Figure BDA0002944797490000114
Figure BDA0002944797490000115
Figure BDA0002944797490000116
Figure BDA0002944797490000117
when P is 0.95 and n is 22, looking up the table D.1 to obtain A1 which is 0.71 and A is less than A1;
the critical interval is 1.82-4.16, and the value B is within the range, so that the data can be accepted as normal distribution. The abnormal values in the experimental data are checked by the Grabbs method, i.e. if the measured value x is in a group of measured valuesiHaving residual error
Figure BDA0002944797490000121
When v isiWhen λ (α, n) s is larger, x isiShould be rejected. In this set of data, the maximum residual is 0.0011, and λ (5%, 22) ═ 2.758, and s ═ 5.40 × 10-4，λ(α，n)s＝2.758×5.40×10-4＝0.0014＞0.0011。
Dixon (Dixon) method: arranging the measurement data from small to large:
X(1)≤X(2)≤···≤X(n-1)≤X(n)
since the number of measurements is 22, r is calculated by the following formula1And rn。
Figure BDA0002944797490000122
If r1＞rnAnd r is1＞f(α，n)Then, X is judged(1)Is an abnormal value; if rn＞r1And r isn＞f(α，n)Then, X is judged(n)Is an abnormal value; if r1And rnAll values are less than f(α，n)Value, then all data is retained.
According to experimental data, the following are calculated: r is1＝0.20，rnLooking up the table to obtain f(α，n)＝0.468。r1And rnAll values are less than f(α，n)Values, therefore this set of data is not anomalous and all data is retained.
Thus, the gas chromatography quantitative result of 4,4' -bromodiphenyl ether was 0.9931.
To sum up, sHPLC＝3.70×10-4，SGC＝5.40×10-4,
Figure BDA0002944797490000123
The Critical Table of the Charcot Kokronen test, C < C (0.05,2,11), indicates that the two sets of data are of equal precision.
The result of the fixed value of the organic purity of the 4,4' -dibromodiphenyl ether pure substance is the average value of two measurement methods, namely:
Figure BDA0002944797490000124
for moisture, the moisture content of the 4,4' -dibromodiphenyl ether purity material candidate was measured by a karl fischer moisture meter. Before testing, the Karl-Lou moisture tester was used to test the standard substance, and the results of the measurement of the standard substance with 0.1% pure water are shown in Table 14.
TABLE 140.1% pure Water Standard substance measurement results
1 2 3 4 5 6 Mean value of Error in indicating value RSD
0.1023 0.1029 0.1042 0.1037 0.1054 0.1039 0.1037 +0.4％ 1.0％
The drift is less than 20 mug/min.
6 samples are extracted, 0.1g of the samples are accurately weighed, Karschner moisture is measured, and the average value is the Karschner moisture content value.
TABLE 154, 4' -Dibromodiphenyl ether moisture measurement results
Sample (I) 1 2 3 4 5 6 Mean value of s
Sample Mass (g) 0.1014 0.1035 0.1027 0.1005 0.1013 0.1006 -- --
Measurement results (%) 0.032 0.029 0.031 0.035 0.034 0.037 0.033 3.60×10-5
The average value of three samples is taken as the final moisture content, and the moisture content of the 4,4' -dibromodiphenyl ether is 0.033%.
For the measurement of inorganic elements, the inorganic elements of the 4,4' -dibromodiphenyl ether purity substance were realized by ICP/MS testing of common inorganic elements. 0.2g of 4,4' -dibromodiphenyl ether is accurately weighed and added into a digestion tube, 5mL of nitric acid and 1mL of 30% hydrogen peroxide are respectively added, and digestion is carried out according to the program set in Table 16.
TABLE 16 digestion program
Step (ii) of Temperature (. degree.C.) Pressure (atm) Time (min)
1 100 15.0 2
2 120 20.0 4
3 150 25.0 4
4 180 30 6
5 200 35 10
6 220 40 10
After the digestion is finished, the inner tank is taken out, and acid is removed until a small amount of residual liquid is left in the solution. Transferring water to a volumetric flask with the constant volume of 25mL, filtering, and measuring 75 elements by ICP/MS (inductively coupled plasma/mass spectrometry) in a semi-quantitative mode, wherein the semi-quantitative concentration is 50 mu g/L. The quantitative limit of the method is 0.1 mu g/L. The elemental contents at measured concentrations greater than 0.1. mu.g/L are shown in Table 17.
TABLE 174, 4' -dibromodiphenyl ether purity standard substance candidate residue cation test results
Element(s) Na Mg S CL K Ca Fe
Blk(ug/L) 14.9 0.8 15.7 5.1 1.5 8.4 2.2
sam(ug/L) 16.6 4.9 28.7 23.1 38.2 0.3 0.6
The concentration of the external standard curve of the common elements is prepared according to the content of the common elements in the digestion solution, which is shown in a table 18.
TABLE 18 concentration of external standard curve of common elements
Element(s) Na Mg S Cl K Ca Fe
Std1(ug/L) 1.0 0.1 1.0 1.0 1.0 0.1 0.1
Std2(ug/L) 5.0 0.5 5.0 5.0 10.0 1.0 1.0
Std3(ug/L) 10.0 1.0 10.0 10.0 100.0 10.0 10.0
Std4(ug/L) 40.0 5.0 40.0 40.0 300.0 50.0 50.0
Std5(ug/L) 80.0 10.0 80.0 80.0 600.0 100.0 100.0
Coefficient of linearity 0.9997 0.9992 0.9991 0.9993 0.9994 0.9995 0.9997
Three bottles of purity standard substance candidates were randomly sampled, 0.2g of each bottle was weighed, and after digestion, ICP/MS quantitative analysis was performed, and the results are shown in Table 19.
TABLE 19 measurement of inorganic elements
Figure BDA0002944797490000131
Taking the average value of the three measured values as the content of inorganic element impurities: 1.55X 10-5。
For solvent residue testing: the solvent which may remain in the raw material of the pure 4,4' -dibromodiphenyl ether during the processing process is dichloromethane, tetrahydrofuran, chloroform, etc. In order to eliminate dichloromethane solvent residue, 25.3mg of 4,4' -dibromodiphenyl ether is accurately weighed, and the volume is determined to be 25mL volumetric flask by n-hexane, and the total ion flow is analyzed by gas chromatography-mass spectrometry, and is shown in FIG. 27. From the analysis results, no solvent other than n-hexane was detected.
Meanwhile, in order to eliminate the solvent residue of n-hexane, 4' -dibromodiphenyl ether solution in dichloromethane with the same concentration is prepared at the same time, and gas chromatography-mass spectrometry analysis is performed to obtain the total ion current as shown in fig. 28. From the analysis results, no solvent other than dichloromethane was detected. Therefore, no solvent remains in the sample with the purity of 4,4' -dibromodiphenyl ether.
Refer to item 6.1 of JJF 1855-.
P＝P0×(1-XW-XV-XNV)
In the formula: p-purity, g/g; p0-the organic purity, calculated by area normalization of the chromatogram, expressed as the ratio of the principal component in the substance to the sum of the principal component and the total amount of structurally related impurities, g/g; xW-moisture content, g/g; xV-volatile component content; xNV-nonvolatile content, g/g.
The 4,4 '-dibromodiphenyl ether purity standard substance candidate takes the influence of sample moisture and residue into consideration, so the fixed value result of the substance mass balance method of the 4,4' -dibromodiphenyl ether purity standard substance candidate is as follows:
PM＝(1-Pwater (W)-PResidue of rice)×PChromatography＝(1-3.3×10-4-1.55×10-5)×0.9940＝0.9935。
Next, when the purity is measured by Differential Scanning Calorimetry (DSC), the differential scanning calorimetry is first calibrated with thermal analysis standard substances such as the national standard substances Ga, In, Sn, Pb, Zn, and the like, and the results of the verification analysis are shown In fig. 29 and fig. 30 by using phenyl salicylate. According to the national marking substance certificate GBW (E)130444, the melting point of phenyl salicylate is 41.82 +/-0.34 ℃, and the heat of fusion is 88.66 +/-0.62J/g. The verification result is consistent with the standard value.
After calibration and verification, the analysis method is optimized, mainly in the optimization of the heating rate and the weighing mass.
Accurately weighing 3.0mg of sample to 0.001mg, spreading on the bottom of aluminum crucible, sealing, placing in DSC instrument, and using 40 μ L standard aluminum empty crucible as reference crucible. Furnace body atmosphere: static air; the purge gas is N240mL/min protective gas: nitrogen, 60 mL/min. Within the range of (melting point + -18) deg.C, 0.3K/min (initial temperature 30 deg.C, heating to 35 deg.C at 10 deg.C/min, heating to 85 deg.C at 0.3 deg.C/min), 0.5K/min (initial temperature 30 deg.C, heating to 42 deg.C at 10 deg.C/min, heating to 85 deg.C at 0.5 deg.C/min), 0.7K/min (initial temperature 30 deg.C, heating to 35 deg.C at 10 deg.C/min, heating to 85 deg.C at a heating rate of 0.7 deg.C/min, heating to 115 deg.C at 1K/min (initial temperature 30 deg.C), the results are shown in FIGS. 31-34, and the results of purity analysis are shown in FIGS. 35-38, respectively. Two samples were tested at each ramp rate and the results are shown in table 20.
TABLE 20 purity measurements at different ramp rates
Figure BDA0002944797490000141
The rapid temperature rise can improve the sensitivity, but the baseline drift is large, the reaction lag is easy to generate, and the separation capability is reduced. A slow temperature increase favors separation, but the sensitivity decreases. It can be seen that within the range of 0.3-1.0K/min, the influence of the temperature rise rate on the purity result is not large, and 0.5K/min is selected as the constant temperature rise rate in consideration of the data dispersibility and the aging effect.
2.0mg, 3.0mg, 4.0mg and 5.0mg of the sample were weighed, spread on the bottom of an aluminum crucible, sealed, and subjected to DSC purity measurement at a temperature rise rate of 0.5K/min, and the influence of the sample weight on the measurement results was examined, with the results shown in Table 21.
TABLE 21 results of purity measurements for different weighed sample masses
Figure BDA0002944797490000151
In this test, the difference between the purity measurements was 0.07% in the test range of 2mg to 5 mg. In general, the sample weighing is too small, the sample weighing error is obvious, and the sample does not uniformly cover the bottom of the crucible. The sample weighing amount is large, and the internal conduction velocity and the temperature gradient of the sample are influenced, so that the resolution is reduced. And on the premise of ensuring the measurement result, the sample weighing amount is reduced as much as possible. The sample weighing amount was finally determined to be 3mg in consideration of the reproducibility of the measurement data and the influence of weighing errors.
According to the finally confirmed experimental conditions: accurately weighing 3.000mg of sample to 0.001mg, spreading on the bottom of aluminum crucible, sealing, placing in DSC instrument, and using 40 μ L standard aluminum empty crucible as reference crucible. Furnace body atmosphere: static air; the purge gas is N240mL/min protective gas: nitrogen, 60 mL/min. The sample is stabilized at-40 ℃ for 30min and heated to 40 ℃ at a heating rate of 0.5K/min. 11 bottles of samples were randomly sampled and tested twice per bottle, and the results of the measurements are shown in Table 22.
TABLE 22 differential scanning calorimetry purity test results
Figure BDA0002944797490000152
Figure BDA0002944797490000161
Carrying out normal distribution test on the measurement data, and calculating a kurtosis coefficient A and a skewness coefficient B as follows:
Figure BDA0002944797490000162
Figure BDA0002944797490000163
Figure BDA0002944797490000164
Figure BDA0002944797490000165
Figure BDA0002944797490000166
when P is 0.95 and n is 22, looking up the table D.1 to obtain A1 which is 0.71 and A is less than A1;
the critical interval is 1.82-4.16, and the value B is within the range, so that the data can be accepted as normal distribution.
The abnormal values in the experimental data are checked by the Grabbs method, i.e. if the measured value x is in a group of measured valuesiHaving residual error
Figure BDA0002944797490000167
When v isiWhen λ (α, n) s is larger, x isiShould be rejected. In this set of data, the maximum residual is 0.0007, and λ (5%, 22) ═ 2.758, and s ═ 3.79 × 10-4，λ(α，n)s＝2.758×3.79×10-4＝0.0010＞0.0007。
Dixon (Dixon) method: arranging the measurement data from small to large:
X(1)≤X(2)≤···≤X(n-1)≤X(n)
since the number of measurements is 22, r is calculated by the following formula1And rn。
Figure BDA0002944797490000168
If r1＞rnAnd r is1＞f(α，n)Then, X is judged(1)Is an abnormal value; if rn＞r1And r isn＞f(α，n)Then, X is judged(n)Is an abnormal value; if r1And rnAll values are less than f(α，n)Value, then all data is retained.
According to experimental data, the following are calculated: r is1＝0.333，rnLooking up the table to obtain f 0.182(α，n)＝0.468。r1And rnAll values are less than f(α，n)Values, therefore this set of data is not anomalous and all data is retained.
The quantitative result of the 4,4' -dibromodiphenyl ether DSC is 0.9956 mol/mol.
Through gas chromatography-mass spectrometry analysis, the impurity component in the 4,4' -dibromodiphenyl ether is 4-bromodiphenyl ether, and the mass fraction of the substance is converted into the mass fraction:
Figure BDA0002944797490000171
the purity values measured by gas chromatography, liquid chromatography and differential scanning calorimetry are subjected to equal precision detection, 11 times of sample measurement are carried out, and the repeatability is as follows: sHPLC＝3.70×10-4，sGC＝5.40×10-4，sDSC＝3.12×10-4，
Figure BDA0002944797490000172
C＜C(0.05,3,11)
Taking the average value of the purity analysis by the mass balance method and the differential scanning calorimetry as a final result, the purity of the 4,4' -dibromodiphenyl ether is:
Figure BDA0002944797490000173
sixth, uncertainty
The total uncertainty consists of three parts: the first part is the uncertainty (. mu.) introduced by 4,4' -dibromodiphenyl ether fixed value experimentConstant value) (ii) a The second part is the uncertainty (. mu.) of the non-uniform generation of the samplebb) (ii) a The third part is the uncertainty (. mu.) due to sample instabilityIts)。
First, the uncertainty introduced by fixed value includes the uncertainty introduced by mass balance method purity fixed value, the uncertainty introduced by differential scanning calorimetry method determination purity and method difference, the uncertainty introduced by weighing, and the uncertainty introduced by constant volume.
According to JJF1855-2020 organic purity standard substance with definite value measurement technical specification of purity standard substance, a measurement model for measuring purity by a mass balance method is as follows: pM＝(1-PWater (W)-PInorganic substance)×PChromatographyTherefore, the evaluation was performed according to the following formula:
Figure BDA0002944797490000174
in the formula: measuring the standard uncertainty of the purity by a mu (M) -4, 4' -dibromodiphenyl ether mass balance method, g/g; mu.srelRelative standard uncertainty for the purity of (P) -4, 4' -dibromodiphenyl ether; mu.srel(PChromatography) -relative standard uncertainty of chromatographic purity of 4,4' -dibromodiphenyl ether; mu.sH2O-standard uncertainty of moisture content; mu.sICP/MSStandard uncertainty of the inorganic element content.
Relative standard uncertainty μ for chromatographic purityrel(PChromatography) Chromatographic purity is an average of gas chromatography and liquid chromatography, and thus, chromatographic uncertainty mainly includes gas chromatography uncertainty introduced, liquid chromatography uncertainty introduced, and process variation uncertainty introduced.
Repeatedly introduced uncertainty mu1,GCIs given by the standard deviation of the measurement, i.e. mu1,GC＝3.70×10-4。
Uncertainty mu introduced by gas chromatography in response to differences2,GCUncertainty introduced by differences in response factors on FID for each compound. Referring to JJF1855-2020, the difference in response factors is calculated as follows:
Figure BDA0002944797490000181
through gas chromatography-mass spectrometry analysis, the impurity component in the 4,4' -dibromodiphenyl ether is 4-bromodiphenyl ether, f0＝0.439，fi0.578. The mol percentage content is converted into the mass percentage content as follows: x is the number ofi＝6.9×10-3。
μ2,GC＝1.68×10-3。
Thus, gas chromatography fixes introduce uncertainties of:
Figure BDA0002944797490000182
the uncertainty introduced by the high performance liquid chromatography comprises the uncertainty introduced by measuring repeatability and the uncertainty introduced by wavelength difference, wherein the repeatability uncertainty is given by standard deviation of a measuring result, mu1,HPLC＝5.08×10-4。
For the uncertainty introduced by the wavelength difference, the purity of 4,4' -dibromodiphenyl ether was analyzed at different wavelengths, and the percentage of the chromatographic peak area of the impurity component at different wavelengths was obtained as shown in table 23.
TABLE 23 area percentages of chromatographic peaks of impurity components at different wavelengths
Wavelength (nm) 210 220 230 240 250 260 260
Content of impurities 0.00701 0.00662 0.00573 0.00526 0.00343 0.00554 0.00686
Content of the main body 0.99299 0.99338 0.99427 0.99474 0.99657 0.99446 0.99314
Thus, the uncertainty introduced by liquid chromatography valuing is:
Figure BDA0002944797490000183
Figure BDA0002944797490000184
thus, uncertainty u introduced in calculating the difference between gas chromatography and liquid chromatography methodsGC-HPLCWhen in use, the uncertainty is introduced by taking the fixed value difference of the gas chromatography and the high performance liquid chromatography as half of the difference of the methods,
Figure BDA0002944797490000185
Figure BDA0002944797490000186
relative standard uncertainty u of chromatographic purityrel(PChromatography)＝uChromatography/PChromatography＝1.30×10-3。
The uncertainty of the moisture measurement is given by the standard deviation of 6 samples: u. ofWater (W)＝3.60×10-5。
The uncertainty introduced by the inorganic element test is supposed to adopt 100% as the relative uncertainty of the inorganic element test, and because the impurity content is small, the final uncertainty influence on the purity of the standard substance is small, so the uncertainty introduced by the residue test is as follows:
uICP/MS＝∑wi×μi＝1.55×10-5
the mass balance method is used for determining the value and introducing the total uncertainty:
Figure BDA0002944797490000191
for differential scanning calorimetry to determine the degree of uncertainty introduced by purity, in the process of measuring the purity of a sample by differential scanning calorimetry, the purity is measured directly by the differential scanning calorimeter, and the purity is measured according to the following formulaAnd (3) calculating: p is 100% -XB，xB＝100％-XBWherein, the purity of P-is g/g; xB-mass fraction of impurities in the organic matter, g/g; x is the number ofB-mass fraction of impurities in the organic matter. Thus, the uncertain evaluation of differential scanning calorimetry of 4,4' -dibromodiphenyl ether is given by the following formula:
Figure BDA0002944797490000192
in the formula: u. of1,DSC-measuring standard uncertainty introduced by repeatability; u. of2,DSCStandard uncertainties introduced by the individual parameters.
For measuring the repeatedly introduced uncertainty, the mass fractions of the substances are 0.9959,0.9956,0.9953,0.9951,0.9954 and 0.9959 according to the 6-time DSC purity measurement result, and the repeatedly introduced uncertainty is: u. of1,DSC＝s＝3.27×10-4。
For the standard uncertainty introduced by each parameter, according to the 4,4' -dibromodiphenyl ether DSC purity measurement method, the uncertain parameters are mainly influenced in the aspects of enthalpy change error, sample weighing, temperature error and conversion of mass fraction and mass fraction of substances.
In the instrument calibration, the melting enthalpy change of the phenyl salicylate serving as a standard substance is calibrated, and the calibration error is 0.13J/g, so that the uncertainty introduced by the enthalpy change error is as follows:
Figure BDA0002944797490000193
when weighing, a mass comparator is adopted, the division value is 0.001mg, the temperature of a basement balance room is 18.6-19.1 ℃, and the relative humidity is 45.8-46.2 RH%. Accurately weighing 3mg of sample by using an aluminum crucible, measuring, weighing three times within 2min, wherein the sample is 3.004mg, 3.006mg and 3.007mg, and uncertainty introduced by weighing stability is as follows: 0.003/3.006 ═ 9.98 × 10-4。
The tolerance of the balance is + -0.005 mg, so that the weighing accuracy of the balance introduces uncertaintyThe degree is 0.005/(2 × 3.006) ═ 8.32 × 10-4。
Figure BDA0002944797490000194
The temperature error of the instrument is +/-0.20 ℃, and the uncertainty introduced by the temperature error is as follows:
Figure BDA0002944797490000201
when converting from mass fraction to mass fraction, one must consider the uncertainty introduced due to the difference in molar mass of the impurities from the host component. The molar mass of water differs greatly from that of 4,4' -dibromodiphenyl ether, so the uncertainty introduced when water is converted from mass fraction to mass fraction must be taken into account. From the results of DSC analysis, an impurity content of 0.44% (mol%), the uncertainty introduced by conversion of the mass fraction of the substance to mass fraction is:
Figure BDA0002944797490000202
synthesizing the above-mentioned uncertainty component,
Figure BDA0002944797490000203
in conclusion, differential scanning calorimetry measures the degree of uncertainty introduced by the purity of 4,4' -dibromodiphenyl ether:
Figure BDA0002944797490000204
the above uncertainty components were synthesized, and the uncertainty introduced by the purity analysis was:
Figure BDA0002944797490000205
the uncertainty introduced by the inter-vial heterogeneity was:
Figure BDA0002944797490000206
μbb＝SH＝3.95×10-4。
from the experimental data (table 6) and the regression variance results (table 7) of the long-term stability of 4,4' -dibromodiphenyl ether, it can be seen from the stability result analysis that the uncertainty contribution of the long-term stability with the expiration date t of 24 months is:
uIts＝sb·t＝2.85×10-5×24＝6.84×10-4。
Figure BDA0002944797490000207
expanding uncertainty: k × UGeneral assembly×100％＝2×2.2×10-3×100％≈0.5％。
The fixed value result of the 4,4' -dibromodiphenyl ether purity standard substance is 99.5 percent, U is 0.5 percent, and k is 2.
At present, the standard substance of 4,4' -dibromodiphenyl ether is not available at home, and the standard substance of 4,4' -dibromodiphenyl ether purity of Accustandard and the solution of 4,4' -dibromodiphenyl ether in 50mg/L isooctane are available at foreign countries. Table 23 shows the conditions and comparison results of some of the similar standard substances at home and abroad.
TABLE 234, 4' -dibromodiphenyl ether as the same standard substance
Figure BDA0002944797490000211
100.4mg of the developed 4,4' -dibromodiphenyl ether is accurately weighed, and diluted by methanol to 100mL to prepare mother liquor. The mother liquor was measured (5 mL) and diluted to a volume of 50mL in a volumetric flask to obtain a solution of 4,4' -dibromodiphenyl ether in methanol (solution A) at a concentration of 99.7 mg/L. 2.53mg of 4,4 '-dibromodiphenyl ether standard substance is accurately weighed, diluted by methanol and fixed to a volume of a 25mL volumetric flask, thus obtaining 101.2mg/L (B) of 4,4' -dibromodiphenyl ether solution in methanol. HPLC analysis is carried out on the two solutions simultaneously, and the liquid chromatography conditions are as follows: c18 column (250mm 4.6mm 5 μm), methanol-water as mobile phase, methanol-water ratio of 90:10 (v: v), detection wavelength of 230nm, sample size of 10 μ L. The results are shown in Table 24.
TABLE 244 situation comparison table of similar standard substance of 4,4' -dibromodiphenyl ether
Figure BDA0002944797490000212
Experimental results show that the developed 4,4 '-dibromodiphenyl ether purity standard substance candidate has accurate quantity value and the characteristics of stability and convenience, can be used as a 4,4' -dibromodiphenyl ether purity standard substance, and is expected to be applied to wider fields.
In conclusion, the preparation method of the 4,4' -dibromodiphenyl ether purity standard substance provided by the invention comprises the steps of selecting raw materials of the standard substance, measuring characteristic quantity values, preparing the standard substance, inspecting uniformity, investigating stability and measuring fixed values; after analysis and determination of the uncertainty component introduced by the homogeneity of the sample, the dispersion of the measurement and other factors, a composite result of the uncertainty of the entire measurement process is given. The stability of the standard substance candidate is examined for 24 months, and the standard substance is proved to be stable; finally, the standard value of the 4,4' -dibromodiphenyl ether purity standard substance is 99.5 percent, the expansion uncertainty is 0.5 percent, and the developed standard substance and the domestic standard substance are compared for experiment, and the result shows that the measurement result of the developed standard substance is consistent with that of the domestic standard substance in the uncertainty range, and the method is stable, convenient and applicable to the measurement of the sample. The development of the series of standard substances can meet the requirements of food, medicine, daily chemicals, environmental protection and chemical product research and detection, and the series of standard substances can be expected to be used for the evaluation of 4,4' -dibromodiphenyl ether related detection and analysis methods and provide favorable guarantee.

Claims (10)

  1. The preparation method of the standard substance of the purity of 4,4' -dibromodiphenyl ether is characterized by comprising the following steps:
    selecting 4,4 '-dibromodiphenyl ether with the purity of more than 99 percent as a purity sample, and respectively adopting gas chromatography-mass spectrometry and nuclear magnetic resonance to carry out qualitative analysis on the 4,4' -dibromodiphenyl ether;
    after a purity sample substance is determined by qualitative analysis, carrying out primary uniformity detection on 4,4 '-dibromodiphenyl ether by adopting a liquid chromatography, wherein the 4,4' -dibromodiphenyl ether subjected to primary uniformity detection is a standard substance candidate;
    and (3) carrying out uniformity inspection, stability inspection and fixed value and uncertainty analysis on the 4,4 '-dibromodiphenyl ether standard substance candidate according to the metrological requirements, wherein if the uniformity, the stability and the uncertainty meet the requirements, the fixed value is accurate and stable, and the standard substance meets the metrological characteristics, namely the 4,4' -dibromodiphenyl ether purity standard substance.
  2. 2. The method according to claim 1, wherein when the gas chromatography-mass spectrometry is performed, the steps of:
    accurately weighing 50.2mg of 4,4 '-dibromodiphenyl ether, and metering the volume to a 50mL brown volumetric flask by using methanol to obtain a solution of 4,4' -dibromodiphenyl ether in methanol with the concentration of 1.04 mg/mL;
    the 4,4' -dibromodiphenyl ether solution in the prepared methanol is analyzed by gas chromatography-mass spectrometry under the following conditions: the sample inlet temperature is 250 ℃, the connection port temperature is 280 ℃, the ion source temperature is 230 ℃, the constant flow mode is 1mL/min, the sample injection amount is 1 muL, the split ratio is 1:10, the scanning range is 50-550, the solvent delay is 3min, the chromatographic column HP-5MS is adopted, the column temperature is 60 ℃, the temperature is increased to 200 ℃ at the temperature rising rate of 5 ℃/min, and the temperature is kept for 22 min.
  3. 3. The method according to claim 1 or 2, wherein the preliminary detection step of homogeneity by liquid chromatography is as follows:
    taking 50.0mg of 4,4 '-dibromodiphenyl ether from the upper part, the middle part and the lower part of a sample bottle filled with the 4,4' -dibromodiphenyl ether respectively, dissolving the 4,4 '-dibromodiphenyl ether in methanol to a volumetric flask with the volume being 25mL by using methanol, and preparing to obtain a solution of the 4,4' -dibromodiphenyl ether in the methanol with the concentration of 2.0 mg/mL;
    a C18 column is adopted, methanol-water with the volume ratio of 90 percent to 10 percent is taken as a mobile phase, the detection wavelength is 230nm, and the purity of the 4,4' -dibromodiphenyl ether is calculated according to the chromatographic peak area.
  4. 4. The method of claim 3, wherein the step of inspecting the homogeneity is as follows:
    randomly extracting 11 bottles of samples from sample bottles filled with 4,4' -dibromodiphenyl ether purity standard substance candidates according to serial numbers of head, tail and middle; weighing 50mg of each bottle of sample, metering the volume to a 50mL volumetric flask by using methanol respectively, preparing a solution of 4,4' -dibromodiphenyl ether in the methanol of 1.0mg/mL, and measuring the purity value of each sample by using a gas chromatograph for 3 times in parallel, wherein the purity value of 3 times of measurement is used as the result of uniformity evaluation.
  5. 5. The method of claim 4, wherein the gas chromatography conditions used to measure the purity value of the measurement by the gas chromatograph are:
    the sample inlet temperature is 250 ℃, the detector temperature is 250 ℃, the constant flow is 6.5mL/min, the sample injection amount is 1 mu L, the split ratio is 1:10, chromatographic column HP-5, column temperature 100 deg.C, keeping for 0.5min, heating to 250 deg.C at a rate of 15 deg.C/min, and keeping for 5 min.
  6. 6. The method of claim 4, wherein the stability test comprises a long-term stability test and a short-term stability test; the long-term stability test step comprises: measuring the 4,4 '-dibromodiphenyl ether purity standard substance solution by adopting a gas chromatograph at different time intervals, fitting a straight line by using x as time and y as the purity of the 4,4' -dibromodiphenyl ether purity standard substance, and judging whether the long-term stability exists according to the slope of the straight line;
    the short-term stability checking step: randomly extracting 6 sample bottles filled with 4,4' -dibromodiphenyl ether purity standard substance candidates, placing at (60 +/-2) DEG C for storage for one week, and measuring the purity; and performing regression analysis according to the purity measurement result to judge whether the short-term stability reaches the standard.
  7. 7. The method according to any one of claims 3 to 6, wherein the determination is performed by mass balance method and differential scanning calorimetry, and the average of the results of the mass balance method and differential scanning calorimetry is taken as the determination.
  8. 8. The preparation method according to claim 7, wherein the specific steps for the mass balance method are as follows: determining organic impurities by gas chromatography and high performance liquid chromatography, determining water content by a Karschner moisture analyzer, determining inorganic element content by ICP/MS, performing solvent residue analysis, and determining a value by mass balance;
    the differential scanning calorimetry method comprises the following specific steps: accurately weighing 3.000mg of a 4,4' -dibromodiphenyl ether purity standard substance candidate, accurately weighing the candidate to 0.001mg, flatly paving the candidate at the bottom of an aluminum crucible, sealing the candidate, placing the candidate in a DSC instrument, and taking a 40 mu L standard aluminum empty crucible as a reference crucible; furnace body atmosphere: static air; the purge gas is N240 mL/min; protective gas: nitrogen gas, 60 mL/min; stabilizing the sample at-40 deg.C for 30min, and heating to 40 deg.C at a heating rate of 0.5K/min; taking 11 bottles of samples which are randomly extracted, testing twice in each bottle, and analyzing and valuing the purity result.
  9. 9. The production method according to claim 7, wherein the uncertainty includes uncertainty introduced by a 4,4' -dibromodiphenyl ether constant value experiment, uncertainty due to nonuniform production of 4,4' -dibromodiphenyl ether, and uncertainty due to unstable production of 4,4' -dibromodiphenyl ether.
  10. 10. 4,4' -dibromodiphenyl ether purity standard substance obtained by the preparation method described in any one of claims 1 to 9.
CN202110189467.5A 2021-02-19 2021-02-19 4,4' -dibromodiphenyl ether purity standard substance and preparation method thereof Pending CN113009011A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114778714A (en) * 2022-03-25 2022-07-22 广东阿格蕾雅光电材料有限公司 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl GC-FID purity analysis method

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7301638B1 (en) * 2004-01-31 2007-11-27 Kla Tencor, Inc. Dimensional calibration standards
CN106832881A (en) * 2017-01-16 2017-06-13 浙江省计量科学研究院 Phthalic ester plasticizer and phosphorus flame retardant standard sample and sample preparation methods in polyurethane
CN107064318A (en) * 2016-07-22 2017-08-18 中南大学 A kind of glycolide standard substance and preparation method thereof and detection method
CN107167529A (en) * 2017-05-03 2017-09-15 浙江省计量科学研究院 The assay method of the Reinheitszahl and uncertainty of phenol and hydroquinones standard substance
KR20180017892A (en) * 2016-08-11 2018-02-21 한국화학연구원 Analytical standard reference consisting of multi-residue pesticides for green peppers with high stability and homogeneity and preparation method thereof
CN108469482A (en) * 2018-03-22 2018-08-31 中华人民共和国汕头出入境检验检疫局检验检疫技术中心 A kind of method that GC-MS measures phosphorus system and bromide fire retardant in PVC simultaneously
CN109678835A (en) * 2019-01-25 2019-04-26 浙江省计量科学研究院 A kind of preparation method of catechin and gallate standard substance

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7301638B1 (en) * 2004-01-31 2007-11-27 Kla Tencor, Inc. Dimensional calibration standards
CN107064318A (en) * 2016-07-22 2017-08-18 中南大学 A kind of glycolide standard substance and preparation method thereof and detection method
KR20180017892A (en) * 2016-08-11 2018-02-21 한국화학연구원 Analytical standard reference consisting of multi-residue pesticides for green peppers with high stability and homogeneity and preparation method thereof
CN106832881A (en) * 2017-01-16 2017-06-13 浙江省计量科学研究院 Phthalic ester plasticizer and phosphorus flame retardant standard sample and sample preparation methods in polyurethane
CN107167529A (en) * 2017-05-03 2017-09-15 浙江省计量科学研究院 The assay method of the Reinheitszahl and uncertainty of phenol and hydroquinones standard substance
CN108469482A (en) * 2018-03-22 2018-08-31 中华人民共和国汕头出入境检验检疫局检验检疫技术中心 A kind of method that GC-MS measures phosphorus system and bromide fire retardant in PVC simultaneously
CN109678835A (en) * 2019-01-25 2019-04-26 浙江省计量科学研究院 A kind of preparation method of catechin and gallate standard substance

Non-Patent Citations (8)

* Cited by examiner, † Cited by third party
Title
ACCUSTANDARD, INC.: "SAFETY DATA SHEET: BDE-015S", 《HTTPS://WWW.ACCUSTANDARD.COM/PROD0008696.HTML》 *
KEBEDE K. KEFENI ET AL: "Analysis of major congeners of polybromobiphenyls and polybromodiphenyl ethers in office dust using high resolution gas chromatography–mass spectrometry", 《CHEMOSPHERE》 *
RUI WANG ET AL: "Photodebromination behaviors of polybrominated diphenyl ethers in methanol/water systems: Mechanisms and predicting descriptors", 《SCIENCE OF THE TOTAL ENVIRONMENT》 *
周瑾艳 等: "差示扫描量热法和质量平衡法测定林丹的纯度", 《食品安全质量检测学报》 *
周瑾艳 等: "酸性橙Ⅱ纯度标准物质的研制", 《计量学报》 *
张庆合 等: "基于质量平衡法的有机物纯度测量技术进展", 《化学试剂》 *
王巧云 等: "丙体六六六纯度标准物质的研制与定值分析", 《化学试剂》 *
马文娟 等: "水环境中污染物同位素溯源的研究进展", 《环境工程技术学报》 *

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114778714A (en) * 2022-03-25 2022-07-22 广东阿格蕾雅光电材料有限公司 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl GC-FID purity analysis method
CN114778714B (en) * 2022-03-25 2024-03-26 广东阿格蕾雅光电材料有限公司 2-dicyclohexylphosphine-2 ',4',6' -triisopropylbiphenyl GC-FID purity analysis method

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