CN105758970A - Method for detecting purity of 3-methylamino-1,2-propandiol by gas chromatography - Google Patents
Method for detecting purity of 3-methylamino-1,2-propandiol by gas chromatography Download PDFInfo
- Publication number
- CN105758970A CN105758970A CN201610325211.1A CN201610325211A CN105758970A CN 105758970 A CN105758970 A CN 105758970A CN 201610325211 A CN201610325211 A CN 201610325211A CN 105758970 A CN105758970 A CN 105758970A
- Authority
- CN
- China
- Prior art keywords
- methylamino
- detection
- gas chromatography
- propanediol
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
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
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/025—Gas chromatography
Abstract
The invention provides a method for detecting the purity of 3-methylamino-1,2-propandiol by gas chromatography. The method comprises the flowing steps: preparing a sample, setting chromatographic conditions and carrying out detection; in the setting of the chromatographic conditions, the column temperature is 240 to 260 DEG C. With the adoption of the method disclosed by the invention, the content of 3-methylamino-1,2-propandiol and the contents of impurities in 3-methylamino-1,2-propandiol can be simultaneously detected and analyzed; the accuracy and precision of analysis data are improved, the repeatability is good and the sensitivity is high; the detection time is short, the operation is easy and simple, and the analysis time of an analyst is saved; the work efficiency is improved; the service life of a chromatographic column is prolonged and the cost is reduced; derivatization is not required, the sample is directly injected after being dissolved by using chromatographically pure methanol to lower the viscosity of the sample.
Description
Technical field
The present invention relates to a kind of gas chromatography determination non-ionic contrast agent Iopromide intermediate 3-methylamino-1,2-
The method of propylene glycol purity, particularly realizes the separation of each impurity component in 3-methylamino-1,2-propanediol, belongs to product instrument
Device analysis technical field.
Background technology
3-methylamino-1,2-propanediol is the important source material of synthesis hypo-osmoticity non-ionic contrast agent Iopromide, and it is pure
Height, the quantity of impurity and the content of degree directly affects purity and the clinical practice of final products Iopromide.At Iopromide
Synthetic reaction in, if 3-methylamino-1,2-propanediol impurity content is higher or impurity component is more, can and intermediate 3-
(2-methoxyl group) acetamido ］-5-(2,3-dihydroxy n-propylamine base formoxyl)-2,4,6-triiodo-benzene formyl chloride occur multiple
Side reaction generates multiple different structure or the complicated product of unknown structure, is injected in vivo and is likely to produce anaphylaxis, symptom
The order of severity differs, and serious symptom can be fatal.Therefore, set up, form reliable and stable 3-methylamino-1,2-propanediol analysis detection side
Method is particularly important.
At present, domestic production producer uses the content of titrimetry detection 3-methylamino-1,2-propanediol mostly, on the one hand divides
Analysis resultant error is relatively big, does not on the one hand reflect structure and the content of impurity, therefore only as simple middle control analysis at all.
Owing to 3-methylamino-1,2-propanediol viscosity is big, boiling point is high, it is analyzed with conventional gas chromatography, composes after direct injected
Figure goes out that peak is wider, lack of standardization and hangover is serious.Domestic gas chromatography is utilized to analyze similar the grinding of 3-methylamino-1,2-propanediol
Study carefully work mainly to have:
Referring to the analysis of homologous series product 3-amino-1,2-PD, Shandong University Master degree candidate Wang Feng is at paper " N, N-
(R_1, R_2)-3-amino-1,2-PD compound catalyze and synthesize research " to propose use in (2010) stainless steel colored
Spectrum post, hydrogen is carrier gas, and FID hydrion flame adds survey device, the gas chromatographic detection 3-methylamino-1,2-propanediol of temperature programming
Method, but the method has following deficiency: (1) spectrogram peak type is the poorest, and hangover is serious；(2) impurity therein is not divided completely
Open；(3) although main peak retention time is maintained at 0.348min, but other impurity does not the most separate, and merely provides 3-methylamine
The purity of base-1,2-PD.
Chinese patent (number of patent application: 201210211135.3, patent name: high-viscosity alcohol is or/and amines gas
Phase chromatographic column pre-treating method) propose the kind high-viscosity alcohol compound gas phase color including 3-methylamino-1,2-propanediol
Spectrum post pre-treating method, also provides analyzing detecting method.The method comprises the following steps: by 0.5～1mL derivatization examination
Agent trifluoroacetic anhydride is placed in 5mL volumetric flask, at 0～5 DEG C add 10～50mg high-viscosity alcohol compounds, vibration 0.5～
1min, 30～60 DEG C of reactions 10～30min, it is cooled to 20～25 DEG C, obtains the sample for gas chromatographic detection.The method
Weak point is: other component in (1) trifluoroacetic anhydride and sample all reacts formation derivant, and testing result is also by three
Impurity in Fluoroethanoic acid acid anhydride is brought into, and owing to the method is that area normalization calculates each constituent content, the accuracy of data is difficult to protect
Card；(2) the detection time is long, from sampling, to trifluoroacetic anhydride derivative reaction to obtaining result, at least needs 60 minutes, operation
Loaded down with trivial details.
Referring to the analysis of homologous series product 3-amino-1,2-PD, Li Qiran, beam immortality is at " analysis and testing technology
With instrument " in JIUYUE, 2006 volume 12 the 3rd phase (P166-170) publishes thesis that " Derivative GC method measures 3-amino-1.2-
The content of propylene glycol " in, set up the method that Derivative GC method measures the content of 3-amino-1,2-PD, by sample
At 50 DEG C, after derivative 30 min, the gas chromatograph SE-54 capillary being furnished with fid detector is used through trifluoroacetic anhydride (TFAA)
Tubing string (30 mm × 0.25, m × 0.25 μm) is measured, although the method has result favorable reproducibility, accuracy is high, method
The advantage such as simple and easy to do, but still have following deficiency: (1) detection time is long, from sampling, to trifluoroacetic anhydride derivative reaction to
To result, at least need 60 minutes；(2) using normal hexane is solvent, and sample is the most insoluble, and trifluoroacetic anhydride derivative reaction exists
Carry out operation complexity under the conditions of frozen water and normal hexane consumption is bigger than normal;(3) trifluoroacetic anhydride all occurs with other component in sample
Reaction forms derivant, and the impurity in trifluoroacetic anhydride is also brought into by testing result, owing to the method is that area normalization calculates
Each constituent content, the accuracy of data is difficult to ensure that.
Referring to the analysis of homologous series product 3-amino-1,2-PD, prunus mume (sieb.) sieb.et zucc. Suning, Yang Jianming, Wang Wei waits in " analysis section
Learn journal " the 2nd phase of volume 29 in April, 2013 publishes thesis " Derivative GC method detection 3-amino-1.2-propylene glycol ", carries
Having gone out and joined in derivatization reagent trifluoroacetic anhydride by 3-amido-1,2-propanediol under frozen water cooling, fully vibrated, 50 DEG C anti-
Answer 30min, after being cooled to room temperature, directly enter gas chromatographic detection, the method for area normalization standard measure, basic ideas and Li Qiran, beam
Method in the paper " content of Derivative GC method mensuration 3-amino-1.2-propylene glycol " of immortality is consistent, does not simply make
With solvent, the derivative compound of trifluoroacetic anhydride is directly entered gas chromatograph inspection side.
Referring to homologous series product 2-amino-1, the analysis of 3-propylene glycol, Wang Yinghua, Hao Wenming " are analyzing test
Room " the 2nd phases 96～98 paper " analysis of serinol capillary gas chromatography " of volume 27 in 2008 propose a kind of deriving
Activating QI GC headspace analysis 2-amino-1, the method for 3-propylene glycol.The method weak point is: detection at least needs 1g
Sample, 5mL derivatization reagent, but also need add 5mL pyridine as catalyst, derivative reaction need after terminating through
Dichloromethane extraction and washing post-processing operation step just can obtain the sample for gas chromatographic detection, and post-processing step is more
Complexity, the detection time is long.
By to 3-methylamino-1,2-propanediol product G C-MS qualitative analysis, product still having 2-methylamino-1,3-third
Glycol, 1,3-dimethylamino-propanol, N, N-(2,3-dihydroxypropyl) methylamine [structural formula CH3N(CH2CHOHCH2OH)2], sweet
The impurity such as oil, polyglycerol (degree of polymerization is generally 2), in the analyzing detecting method that prior art provides, basic point be unable to do without or divides
From not going out impurity therein.
Summary of the invention
Gas chromatography analysis detection is used to exist based on domestic existing 3-methylamino-1,2-propanediol and homologue thereof
Problems, the present invention provide a kind of fast and convenient, measure the gas of each component in 3-methylamino-1,2-propanediol product simultaneously
Analysis of hplc method, to realize following goal of the invention:
(1) can detect simultaneously analyze the content of main component 3-methylamino-1,2-propanediol and 2-methylamino-1,3-the third two
Alcohol, 1,3-dimethylamino-propanol, N, N-(2,3-dihydroxypropyl) methylamine [structural formula CH3N(CH2CHOHCH2OH)2], glycerol,
The content of the impurity such as polyglycerol (degree of polymerization is generally 2)；
(2) present invention analyzes method, and good linearity, the response rate are high, and precision is high, reproducible；
(3) the detection time is short, easy and simple to handle, saves the analysis time of analysis personnel；Improve work efficiency；
(4) extend the service life of chromatographic column, reduce cost；
(5) it is made without derivatization, after reducing sample viscosity, directly notes sample；
For solving the technical problem that prior art exists, the present invention takes techniques below scheme:
The method of a kind of gas chromatography detection 3-methylamino-1,2-propanediol purity, described method, including sample preparation, color
The setting of spectral condition, detection operation.
The following is and the further of technique scheme is improved:
The setting of described chromatographic condition, column temperature is 240-260 DEG C；
Column temperature is preferably 255-260 DEG C；
Column temperature is preferably 260 DEG C；
The setting of described chromatographic condition, the flow velocity of carrier gas nitrogen is 30-40mL/min；
The flow velocity of carrier gas nitrogen is preferably 30-32 mL/min；
The flow velocity of carrier gas nitrogen is preferably 30 mL/min；
Described nitrogen, purity is more than 99.999%.
The setting of described chromatographic condition, temperature of vaporization chamber is 280-320 DEG C；
Temperature of vaporization chamber is preferably as 315-320 DEG C；
Temperature of vaporization chamber is 320 DEG C；
The setting of described chromatographic condition, detector temperature is 280-320 DEG C；
Detector temperature is preferably 315-320 DEG C；
Detector temperature is preferably 320 DEG C；
The setting of described chromatographic condition, chromatographic column is quartz capillary column, and pillar specification is 30m × 0.32mm × 0.5um.
The setting of described chromatographic condition, split sampling, split ratio 20:1；Air velocity is 450 mL/min；Hydrogen stream
Speed is 45mL/min.
Described hydrogen, purity is more than 99.99%；
Described air, for purifying air；
Described sample prepares, and solvent is Chromatographic Pure Methanol.
Described detection operation, stablizes the steadily rear sample introduction analysis of 0.5 little base line, and sample size is 0.2 μ L.
Described sample introduction, uses microsyringe；The specification of described microsyringe is 2 μ L or 1 μ L；
Described detection method, the gas chromatograph of employing, it is furnished with flame ionization ditector and chromatographic data processor, sensitive
Degree and stability should meet the regulation of GB9722；
Described chromatograph, model is that plant resources in Wenling produces FL9790.
Compared with prior art, the invention have the benefit that
1, the present invention analyzes method, and the 2-methylamino generated in for the first time 3-methylamino-1,2-propanediol being synthesized in industry-
1,3-PD, 1,3-dimethylamino-propanol, N, N-(2,3-dihydroxypropyl) methylamine [structural formula CH3N
(CH2CHOHCH2OH)2], glycerol, polyglycerol (degree of polymerization is generally 2) be kept completely separate.
2, using Chromatographic Pure Methanol to dissolve full-bodied 3-methylamino-1,2-propanediol, reduce sample viscosity, sample is molten
Sample can be directly noted after solution, easy and simple to handle, compared with the derivative compound of existing use trifluoroacetic anhydride note sample, do not bring impact inspection into
Surveying the impurity of result accuracy, testing result truly reflects the content of each component in 3-methylamino-1,2-propanediol.
3, the detection time is short.The method using the present invention detects, and obtains chromatograph testing result from being sampled to, it is only necessary to
10-15 minute；Use the derivatization of trifluoroacetic anhydride, from being sampled to obtain chromatograph testing result, at least need 50-60 minute,
Either check analysis or middle control, use manpower and material resources sparingly, save the time, for instructing pilot process control and adjustment
Technological parameter has great significance.
4, owing to there being Micro Amounts of Chlorine (Cl) to exist in finished product 3-methylamino-1,2-propanediol, stainless steel is had necessarily by chlorine
Corrosivity, select capillary column to replace stainless steel column, it is to avoid corrosion, relatively extend the service life of chromatographic column, relatively
Reduce product analysis cost.Under normal operating condition, capillary column can use 1 year and stainless steel column used about half a year
The detection bigger pillar needing more to renew of data deviation i.e. occurs；Compared with the derivative compound note sample using trifluoroacetic anhydride, often
Individual sample analysis saves reagent about 3 yuan.
5, the present invention selectes chromatographic column and chromatographic condition, each component can preferably separate and go out peak, uses 3-first
Amido-1,2-PD standard substance are linear equation, r=0.997；Detection range is wide, and the inventive method is in 10～50mg scopes
Internal linear is good；Average recovery rate is 99.5-99.6%, adds the 3-methylamino-1,2-propanediol standard substance of 5.0mg, 20mg
Carry out 5 parallel tests, with mean value calculation relative standard deviation after analysis, respectively 2.62%, 0.968%；Precision is high, right
Same sample carries out 5 parallel assays, and the relative standard deviation of peak area is 0.285%.
Owing to 3-methylamino-1,2-propanediol and impurity therein are polar molecule, except glycerol and N, N-(2,3-
Dihydroxypropyl) methylamine is with 3-methylamino-1,2-propanediol boiling-point difference higher than more than 20 DEG C, and 2-methylamino-1,3-PD is
The isomers of 3-methylamino-1,2-propanediol, boiling point is close, and separating difficulty is relatively big, therefore, selected suitable chromatographic column,
The operating parameters such as column temperature, carrier gas and flow velocity are particularly important.
6, column temperature of the present invention uses constant temperature, low boiling component and high boiling component have in the chromatography column suitable reservation,
Chromatographic peak is evenly distributed and peak shape is symmetrical, time-consuming, it is to avoid in temperature programmed work, a sample needle runs complete, also to enter
Row cooling waits that i.e. analysis cools down and is stabilized to original state and needs parameters change in a period of time, temperature-rise period after terminating
Higher to instrument requirements, baseline is difficult to stable deficiency；Instrument stabilizer, baseline stability, the interval of twice analysis is short, goes wrong
Lookup reason is relatively easy.Controlling temperature (constant temperature) main purpose is to eliminate temperature to appearance time, sensitivity, baseline stability
Impact.
Accompanying drawing illustrates:
The chromatogram that detection method described in Fig. 1: embodiment 2 is corresponding；
The chromatogram that detection method described in Fig. 2: embodiment 3 is corresponding；
The chromatogram that detection method described in Fig. 3: embodiment 4 is corresponding；
The chromatogram that detection method described in Fig. 4: embodiment 5 is corresponding；
The chromatogram that detection method described in Fig. 5: embodiment 6 is corresponding.
In Fig. 1, owing to separating effect is the best, retention time be the material of 2.618min be 3-methylamino-1,2-propanediol
Mixed with two kinds of low-boiling compounds 1,3-dimethylamino-propanol and 2-methylamino-1,3-PD one of which or two kinds
Compound；Retention time be the material of 3.902min for being probably glycerol or glycerol and N, N-(2,3-dihydroxypropyl) methylamine mixed
Compound；Retention time be the material of 4.168min be polyglycerol (degree of polymerization is generally 2) or polyglycerol and N, N-(2,3-bis-
Hydroxypropyl) mixture of methylamine；
In Fig. 2, retention time be the material of 2.615min be 3-methylamino-1,2-propanediol；Owing to separating effect is the best, retain
Time be the material of 2.237min be 1,3-dimethylamino-propanol, or 2-methylamino-1,3-PD, or 1,3-dimethylamino-
Propanol and the mixture of 2-methylamino-1,3-propylene glycol；Owing to separating effect is the best, retention time is that the material of 3.847min is
Glycerol or glycerol and the mixture of N, N-(2,3-dihydroxypropyl) methylamine；Retention time is that the material of 4.068min is sweet for polymerization
Oily (degree of polymerization is generally 2) or polyglycerol and the mixture of N, N-(2,3-dihydroxypropyl) methylamine；
In Fig. 3, retention time be the material of 2.647min be 3-methylamino-1,2-propanediol；Owing to separating effect is the best, boiling point
Two kinds of low components are still not separated by, retention time be the material of 2.412min be 1,3-dimethylamino-propanol, or 2-methylamine
The mixture of base-1,3-PD, or 1,3-dimethylamino-propanol and 2-methylamino-1,3-PD；Adjust operating condition
After, high boiling three kinds of materials are kept completely separate, retention time be the material of 3.072min be N, N-(2,3-dihydroxy third
Base) methylamine；Retention time be the material of 3.892min be glycerol；Retention time be the material of 4.123min be that polyglycerol is (poly-
Right generally 2)；
In Fig. 4, owing to again have selected operating condition, all components in sample are kept completely separate.Retention time is 1.870min
Material be 2-methylamino-1,3-propylene glycol；Retention time be the material of 2.250min be 1,3-dimethylamino-propanol；Retain
Time be the material of 2.622min be 3-methylamino-1,2-propylene glycol；Retention time be the material of 3.047min be N, N-(2,3-
Dihydroxypropyl) methylamine；Retention time be the material of 3.867min be glycerol；Retention time is that the material of 4.100min is for being polymerized
Glycerol (degree of polymerization is generally 2).
In Fig. 5, Japan's sample to go out peak similar with embodiment 4, each proximate analysis is clear.Retention time is 1.858min
Material be 2-methylamino-1,3-propylene glycol；Retention time be the material of 2.388min be 1,3-dimethylamino-propanol；Retain
Time be the material of 2.615min be 3-methylamino-1,2-propylene glycol；Retention time be the material of 3.035min be N, N-(2,3-
Dihydroxypropyl) methylamine；Retention time be the material of 3.847min be glycerol；Retention time is that the material of 4.068min is for being polymerized
Glycerol (degree of polymerization is generally 2).
Wherein in Fig. 1-3, retention time peak before 2min be Chromatographic Pure Methanol go out peak；In Fig. 4, retention time exists
Peak before 1.870min be Chromatographic Pure Methanol go out peak；In Fig. 5, retention time peak before 1.858min is chromatographically pure first
Alcohol go out peak.
Detailed description of the invention:
It should be understood that embodiment 2-5 is same 3-methylamino-1,2-propanediol sample, simply GC conditions is not
With；
Embodiment 1 solvent screening is tested
Owing to 3-methylamino-1,2-propanediol viscosity is relatively big, direct injected can not be by the impurity in 3-methylamino-1,2-propanediol
Separate, therefore consider the viscosity using solvent dilution to reduce sample introduction.
Applicant has selected ethanol, acetone, trichloroethane, normal hexane etc. to dissolve 3-methylamino-1,2-propanediol, identical
Testing conditions under be analyzed experiment.
When using acetone, acetone reacts with 3-methylamino-1,2-propanediol, gradually by nothing in the sample short time rapidly
Complexion changed is light yellow, and detection each component peak overlapping of collection of illustrative plates is difficult to separately；
Use ethanol and trichloroethane, although Main Components 3-methylamino-1,2-propanediol separating effect is preferable, but occur or
Low-boiling-point substance (referring to that boiling point is less than the component of 3-methylamino-1,2-propanediol) is inseparable or high-boiling components (refers to that boiling point is higher than 3-methylamine
The component of base-1,2-PD) do not go out the phenomenon at peak, and when to use trichloroethane be solvent, hangover is serious；
When employing normal hexane is solvent, owing to 3-methylamino-1,2-propanediol dissolubility is the lowest, each component appearance time repeats
Property is poor, and Main Components peak type is asymmetric, and precision of analysis is impacted.
Through repeatedly testing, finally determining use Chromatographic Pure Methanol is solvent, have selected suitable color on this basis
Spectrum post, it is determined that optimum chromatogram condition and operating parameter, easy and simple to handle, analytical data is accurate, component peaks good separating effect, weight
Existing property is good, defines complete detection technique method.
The method of 2 one kinds of gas chromatography detection 3-methylamino-1,2-propylene glycol purity of embodiment
Comprise the following steps:
1, sample prepares
3-methylamino-1,2-propanediol about 0.1mL is dissolved in 2mL Chromatographic Pure Methanol, standby after fully dissolving.
2, the setting of chromatographic condition
(1) chromatograph (plant resources in Wenling produces FL9790)；
(2) detector (FID), flame ionization ditector；
(3) Agilent gas chromatographic column, DB-1701(30m × 0.32mm × 0.5um) quartz capillary column；
(4) column temperature, 240 DEG C；Sampling volume is 0.2 L, split sampling, split ratio 20:1；Carrier gas nitrogen, flow velocity 40mL/
min ；Air velocity 450 mL/min；Hydrogen 45mL/min；
(5) temperature of vaporization chamber, 280 DEG C；
(6) detector temperature, 280 DEG C.
3, detection operation
Switch on power start by chromatograph, must work as detector temperature and be raised to design temperature and light a fire；Stablize 0.5 little base line
Sample introduction analysis after steadily；Taking in 0.2 μ L sample injection gas chromatography instrument, record chromatogram, to the twice of main peak retention time, is pressed
Area normalization method calculates 3-methylamino-1,2-content of propylene glycol；
Analysis result is shown in accompanying drawing 1 and table 1.
Table 1 uses the testing result that the analysis method of embodiment 2 is corresponding
Wherein peak number 1 is 3-methylamino-1,2-propanediol and two kinds of low-boiling compounds 1,3-dimethylamino-propanol and 2-
Methylamino-1,3-propylene glycol one of which or the mixture of two kinds；Peak number 2 is probably glycerol or glycerol and N, N-(2,3-dihydroxies
Base propyl group) mixture of methylamine；Peak number 3 is probably polyglycerol (degree of polymerization is generally 2) or polyglycerol and N, N-(2,3-bis-
Hydroxypropyl) mixture of methylamine；
Early stage is by 3-methylamino-1,2-propanediol product G C-MS qualitative analysis, still having 2-methylamino-1,3-third in product
Glycol, 1,3-dimethylamino-propanol, N, N-(2,3-dihydroxypropyl) methylamine [structural formula CH3N(CH2CHOHCH2OH)2], sweet
The impurity such as oil, polyglycerol (degree of polymerization is generally 2), when analysis testing conditions is suitable, several components all should go out peak.But by attached
Fig. 1 and Biao 1 is it can be seen that before main peak in addition to solvent methanol goes out peak, boiling point is less than two of 3-methylamino-1,2-propanediol
Component 2-methylamino-1,3-PD, 1,3-dimethylamino-propanol does not the most go out peak, combines with main peak；Boiling point is higher than
Three Component seperation effects of 3-methylamino-1,2-propanediol are bad, and three components are merged into two components and go out peak.Here it is color
" losing peak " and " peak overlapping " phenomenon common in analysis of spectrum.By analyzing comprehensively, it is primarily due to column temperature setting improper,
Column temperature is on the low side.
Column temperature, i.e. chromatogram column temperature, be three important temperatures (vaporizer temperature, column oven temperature and the inspection of gas chromatogram
One of survey device temperature), also it is a most important temperature, is one of important parameter affecting gas chromatogram separation, directly affects
Separation efficiency and analysis speed.
Chromatogram column temperature, not only affects the Thermodynamics of chromatographic process, also affects the kinetic factor of mass transport process.Post
Temperature change, not only affects post forefront pressure, flow rate of carrier gas etc., it is often more important that separation, the analysis result of material is brought impact.
The impact of separation efficiency and analysis time is by column temperature: if column temperature is too high, and can make the partition coefficient K value of each component
Diminishing, separating degree reduces；But column temperature is too low, mass transfer rate significantly reduces, and column efficiency declines, and can extend analysis time；
The impact of Compound Retention time is by column temperature: column temperature is the highest, goes out peak the fastest, and retention time diminishes；Column temperature change can be made
The repeatability becoming retention time is bad, thus affects the qualitative results of sample component.
The impact of chromatographic peak peak shape is by column temperature: column temperature raises, and half-peak breadth can be caused under normal circumstances to narrow, and peak height becomes
Height, peak area is constant.But component peak height uprises, when carrying out quantitative with peak height, analysis result may produce change；Otherwise column temperature
Reduce, the most on the contrary.
The method of 3 one kinds of gas chromatography detection 3-methylamino-1,2-propylene glycol purity of embodiment
Comparison: on the basis of the method for embodiment 2, only change column temperature, do not change temperature of vaporization chamber, only heightens 260 by column temperature
DEG C, experimental result: the low-boiling-point substance before main peak goes out peak, but it is the most inconspicuous to go out peak, and separating effect is very poor；Three should be had after main peak
Component go out peak, result only has the peak of two components.
Analyzing reason is that temperature of vaporization chamber is on the low side.According to the universal law of gas chromatographic analysis, the temperature of injection port wants height
Boiling point in analyte, it is ensured that all analytes can be gasified totally after injection port sample introduction.Injector temperature is that GC divides
The prerequisite of analysis, the too high sample of temperature decomposes, and material may be lost or cracking；Too low, analysans gasification is not exclusively.
Therefore, applicant determines on the basis of embodiment 2, improves column temperature and temperature of vaporization chamber simultaneously, and concrete steps are such as
Under:
Comprise the following steps
1, sample prepares
3-methylamino-1,2-propanediol about 0.1mL is dissolved in 2mL Chromatographic Pure Methanol, standby after fully dissolving；
2, the setting of chromatographic condition
(1) chromatograph (plant resources in Wenling produces FL9790)；
(2) detector (FID), flame ionization ditector；
(3) Agilent gas chromatographic column, DB-1701(30m × 0.32mm × 0.5um) quartz capillary column
(4) column temperature, 260 DEG C；Sampling volume is 0.2 L, split sampling, split ratio 20:1；Carrier gas nitrogen, flow velocity 40mL/
min ；Air velocity 450 mL/min；Hydrogen 45mL/min；
(5) temperature of vaporization chamber, 320 DEG C；
(6) detector temperature, 280 DEG C.
3, detection operation
Switch on power start by chromatograph, must work as detector temperature and be raised to design temperature and light a fire.Stablize 0.5 little base line
Sample introduction analysis after steadily.
Taking in 0.2 μ L injection gas chromatography instrument, the twice of record chromatogram to main peak retention time, based on area normalization method
Calculate 3-methylamino-1,2-content of propylene glycol.Analysis result is shown in accompanying drawing 2 and table 2.
Table 2 uses the testing result that the detection method of embodiment 3 is corresponding
Inferring according to retention time, peak number 1 is 1,3-dimethylamino-propanol, or 2-methylamino-1,3-PD, or 1,3-bis-
Methylamino-propanol and the mixture of 2-methylamino-1,3-propylene glycol；Peak number 2 is 3-methylamino-1,2-propanediol；Owing to separating
Poor effect, peak number 3 is glycerol or glycerol and the mixture of N, N-(2,3-dihydroxypropyl) methylamine；Peak number 4 is polyglycerol
(degree of polymerization is generally 2) or polyglycerol and the mixture of N, N-(2,3-dihydroxypropyl) methylamine；
By accompanying drawing 2 and table 2 it can be seen that raising column temperature to 260 DEG C, temperature of vaporization chamber bring up to 320 DEG C, the low-boiling-point substance before main peak
Go out peak, although not by two kinds of compounds separately, but be separated clearly with main peak, show to improve temperature of vaporization chamber to low-boiling-point substance group
Part separates effectively.
The method of 4 one kinds of gas chromatography detection 3-methylamino-1,2-propylene glycol purity of embodiment
Analyze the testing result of embodiment 3, although the low-boiling-point substance before main peak goes out peak, but still is not separated by two kinds of compounds,
And only occurring two component peaks after main peak, analyze the selection of reason carrier gas nitrogen speed improper, flow rate of carrier gas is too high.
Flow rate of carrier gas is one of major reason determining chromatographic isolation.Generally flow velocity height chromatographic peak is narrow, otherwise the widest,
But flow velocity is too high or too low has adverse influence to separating.Flow rates demand is wanted steadily.When column temperature is constant, flow velocity has one to peak shape
Fixed impact, the too small meeting of flow velocity makes peak trail, and crosses conference and makes peak shape distortion.Certainly the retention time to peak is the size with flow velocity
It is directly proportional.During constant flow rate, appropriateness increases column temperature can have certain help to improving peak shape；When condition, reached must
When asking, several sample main peak separating degrees measured under selected temperature conditions all meet the requirements, but total retention time
Oversize, the most adjacent two peak-to-peak every the most remote, it is possible to by adjusting flow velocity to shorten the retention time at all of peak simultaneously: at stream
Speed constant in the case of, column temperature raise, retention time will premise, temperature reduce, retention time is moved the most after the meeting.
Therefore, applicant determines on the basis of embodiment 3, only changes the flow velocity of carrier gas, by the flow velocity of carrier gas by
45mL/min is reduced to 30ml/min；Concrete operations are as follows:
Comprise the following steps:
1, sample prepares
3-methylamino-1,2-propanediol about 0.1mL is dissolved in 2mL Chromatographic Pure Methanol, standby after fully dissolving.
2, chromatographic condition
(1) chromatograph (plant resources in Wenling produces FL9790)；
(2) detector (FID), flame ionization ditector；
(3) Agilent gas chromatographic column, DB-1701(30m × 0.32mm × 0.5um) quartz capillary column
(4) column temperature, 260 DEG C；Sampling volume is 0.2 L, split sampling, split ratio 20:1；Carrier gas nitrogen, flow velocity 30mL/
min ；Air velocity 450 mL/min；Hydrogen 45mL/min；
(5) temperature of vaporization chamber, 320 DEG C；
(6) detector temperature, 280 DEG C.
3, detection operation
Switch on power start by chromatograph, must work as detector temperature and be raised to design temperature and light a fire；Stablize 0.5 hour limit
Sample introduction analysis after steadily；Taking in 0.2 μ L injection gas chromatography instrument, the twice of record chromatogram to main peak retention time, by area
Normalization method calculates 3-methylamino-1,2-content of propylene glycol.Analysis result is shown in accompanying drawing 3 and table 3.
Table 3 uses the testing result that the detection method of embodiment 4 is corresponding
Wherein, in table 3, peak number 2 is 3-methylamino-1,2-propanediol；Owing to separating effect is the best, peak number 1 is 1,3-dimethylamine
The mixing of base-propanol, or 2-methylamino-1,3-PD, or 1,3-dimethylamino-propanol and 2-methylamino-1,3-PD
Thing；After adjusting operating condition, high boiling three kinds of materials are kept completely separate, and peak number 3 is N, N-(2,3-dihydroxypropyl) first
Amine；Peak number 4 be the material of 3.892min be glycerol；Peak number 5 is polyglycerol (degree of polymerization is generally 2)；
By accompanying drawing 3 and table 3 it can be seen that after main peak three components be kept completely separate, illustrate adjust flow rate of carrier gas the most suitable.
The method of 5 one kinds of gas chromatography detection 3-methylamino-1,2-propylene glycol purity of embodiment
The result of embodiment 4, it is known that part low boiling component does not go out peak, preliminary judgement is the reason that detector temperature is on the low side.Inspection
Survey device and the junction from chromatographic column to detector all must make the liquid phase of sample and loss occur without condensation, if detector temperature
Spend the lowest, after sample condensation, arise that the phenomenon that chromatographic peak is lost.The generally He Gefeng decay of widening at peak condenses work exactly
Sign.
On the basis of embodiment 4, only change detector temperature, detector temperature is improved to 320 DEG C, concrete operations
As follows:
1, sample prepares
3-methylamino-1,2-propanediol about 0.1mL is dissolved in 2mL Chromatographic Pure Methanol, standby after fully dissolving.
2, chromatographic condition
(1) chromatograph (plant resources in Wenling produces FL9790)；
(2) detector (FID), flame ionization ditector；
(3) Agilent gas chromatographic column, DB-1701(30m × 0.32mm × 0.5um) quartz capillary column
(4) column temperature, 260 DEG C；Sampling volume is 0.2 L, split sampling, split ratio 20:1；Carrier gas nitrogen, flow velocity 30mL/
min ；Air velocity 450 mL/min；Hydrogen 45mL/min；
(5) temperature of vaporization chamber, 320 DEG C；
(6) detector temperature, 320 DEG C.
3, detection operation
Switch on power start by chromatograph, must work as detector temperature and be raised to design temperature and light a fire.Stablize 0.5 hour limit
Sample introduction analysis after steadily.Taking in 0.2 μ L injection gas chromatography instrument, the twice of record chromatogram to main peak retention time, by area
Normalization method calculates 3-methylamino-1,2-content of propylene glycol.Analysis result is shown in accompanying drawing 4 and table 4.
Table 4 uses the testing result that the detection method of embodiment 5 is corresponding
Wherein, in table 4, peak number 1 to peak number 6 be followed successively by 2-methylamino-1,3-PD, 1,3-dimethylamino-propanol, 3-methylamine
Base-1,2-PD, N, N-(2,3-dihydroxypropyl) methylamine, glycerol, polyglycerol (degree of polymerization is generally 2).
By accompanying drawing 4 and table 4 it can be seen that detector temperature is brought up to 320 DEG C after, all components are separated clearly, all
Going out peak, peak type is preferable.
The detection of embodiment 6 standard substance
Accurately weigh 3-methylamino-1 of ormal weight, 2-propylene glycol standard substance (Japan's import sample), as described in Example 5
Carry out gas chromatographic detection, after sample introduction, calculate 3-methylamino-1,2-by area normalization method (station data automatically processes)
The content of propylene glycol is tri-sample introduction result meansigma methodss of 99.81%(), with 3-methylamino-1 bought, 2-propylene glycol standard substance
Content >=99.80% of upper mark is consistent.
The testing result of table 5 standard substance
Wherein, in table 5, peak number 1 to peak number 6 be followed successively by 2-methylamino-1,3-PD, 1,3-dimethylamino-propanol, 3-methylamine
Base-1,2-PD, N, N-(2,3-dihydroxypropyl) methylamine, glycerol, polyglycerol (degree of polymerization is generally 2).
All components are separated clearly, and all go out peak, and peak type is preferable.
Embodiment 7 range of linearity analysis
Accurately weigh 3-methylamino-1 of ormal weight, 2-propylene glycol standard substance (Japan's import sample), as described in Example 5
Carrying out gas chromatographic detection, data are as shown in table 6.Its linear equation is: y=13816x-12172, r=0.997, this method
In the range of 10～50mg the most well.
Described 3-methylamino-1,2-propylene glycol standard substance, weight/mass percentage composition is more than 99.80% (GC), japanese product.
3-methylamino-1 that x-adds, the amount of 2-propylene glycol standard substance；
Y-is peak area.
Table 6 linear equation experimental data
Embodiment 8 determination of recovery rates
Being separately added into 3-methylamino-1 of 5.0mg, 20mg in the sample of known content, 2-propylene glycol standard substance (enter by Japan
Mouthful sample, measures 5 times the most respectively, response rate scope at 99.5%-99.6%, its response rate, relative standard
Deviation RSD is shown in Table 7.
Described 3-methylamino-1,2-propylene glycol standard substance, weight/mass percentage composition is more than 99.80% (GC), japanese product.
Table 7 response rate data
The experiment of embodiment 9 precision
As described in Example 5, under same experimental conditions, same sample is carried out 5 parallel assay (3-methylamines of configuration
Base-1,2-PD sample size is 20mg/mL), measurement result is shown in Table 8.
Table 8 precision test data
Finally it is noted that the foregoing is only the preferred embodiments of the present invention, it is not limited to the present invention, although
Being described in detail the present invention with reference to previous embodiment, for a person skilled in the art, it still can be right
Technical scheme described in foregoing embodiments is modified, or wherein portion of techniques feature is carried out equivalent.All
Within the spirit and principles in the present invention, any modification, equivalent substitution and improvement etc. made, should be included in the protection of the present invention
Within the scope of.
Claims (9)
1. the method for a gas chromatography detection 3-methylamino-1,2-propanediol purity, it is characterised in that: described method, bag
Include sample preparation, the setting of chromatographic condition, detection operation.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levying and be: the setting of described chromatographic condition, column temperature is 240-260 DEG C.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levying and be: the setting of described chromatographic condition, the flow velocity of carrier gas nitrogen is 30-40mL/min.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levying and be: the setting of described chromatographic condition, temperature of vaporization chamber is 280-320 DEG C.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levying and be: the setting of described chromatographic condition, detector temperature is 280-320 DEG C.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levying and be: the setting of described chromatographic condition, chromatographic column is quartz capillary column, and pillar specification is 30m × 0.32mm × 0.5um.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levy and be: the setting of described chromatographic condition, split sampling, split ratio 20:1；Air velocity is 450 mL/min；Hydrogen stream
Speed is 45mL/min.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levy and be: described sample prepares, and solvent is Chromatographic Pure Methanol.
The method of a kind of gas chromatography the most according to claim 1 detection 3-methylamino-1,2-propanediol purity, it is special
Levying and be: described detection operation, stablize the steadily rear sample introduction analysis of 0.5 little base line, sample size is 0.2 μ L.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610325211.1A CN105758970B (en) | 2016-05-17 | 2016-05-17 | A kind of method of gas chromatography detection 3- methylamino -1,2- propane diols purities |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201610325211.1A CN105758970B (en) | 2016-05-17 | 2016-05-17 | A kind of method of gas chromatography detection 3- methylamino -1,2- propane diols purities |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN105758970A true CN105758970A (en) | 2016-07-13 |
| CN105758970B CN105758970B (en) | 2018-05-15 |
Family
ID=56324037
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201610325211.1A Expired - Fee Related CN105758970B (en) | 2016-05-17 | 2016-05-17 | A kind of method of gas chromatography detection 3- methylamino -1,2- propane diols purities |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN105758970B (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112782304A (en) * | 2020-12-28 | 2021-05-11 | 广东肇庆星湖生物科技股份有限公司 | Capillary gas chromatography analysis method of dimethylamino-2-propanol |
| CN113030353A (en) * | 2019-12-25 | 2021-06-25 | 上海奥博生物医药技术有限公司 | Method for measuring content of (S) -1, 2-propylene glycol chiral isomer |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004013123A1 (en) * | 2002-08-01 | 2004-02-12 | Basf Aktiengesellschaft | Method for the production of (s)-3-methylamino-1-(thien-2-yl)propan-1-ol |
| CN101759574A (en) * | 2009-12-25 | 2010-06-30 | 张中法 | Synthesizing method of 3-methylamino-1, 2-propanediol |
| CN102721771A (en) * | 2012-06-26 | 2012-10-10 | 西安近代化学研究所 | Gas chromatographic column pretreatment method for high-viscosity alcohol or/and amines |
| CN104829466A (en) * | 2015-05-11 | 2015-08-12 | 泰山医学院 | Method of synthesizing 3-methylamino-1,2-propylene glycol by pipeline reactor |
| CN104844463A (en) * | 2015-05-19 | 2015-08-19 | 泰山医学院 | Green synthetic method of high-purity 3-methylamino-1,2-propandiol |
| KR20150122876A (en) * | 2014-04-23 | 2015-11-03 | 한국건설기술연구원 | Water treatment apparatus of chlorine-uv combined oxidation for removing algae-caused noxious substance, and variable control method of chlorine dosage and uv dose using the same |
| CN105254521A (en) * | 2015-10-27 | 2016-01-20 | 遵义医学院 | Preparation technology of iopromide intermediate |
-
2016
- 2016-05-17 CN CN201610325211.1A patent/CN105758970B/en not_active Expired - Fee Related
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2004013123A1 (en) * | 2002-08-01 | 2004-02-12 | Basf Aktiengesellschaft | Method for the production of (s)-3-methylamino-1-(thien-2-yl)propan-1-ol |
| CN101759574A (en) * | 2009-12-25 | 2010-06-30 | 张中法 | Synthesizing method of 3-methylamino-1, 2-propanediol |
| CN102721771A (en) * | 2012-06-26 | 2012-10-10 | 西安近代化学研究所 | Gas chromatographic column pretreatment method for high-viscosity alcohol or/and amines |
| KR20150122876A (en) * | 2014-04-23 | 2015-11-03 | 한국건설기술연구원 | Water treatment apparatus of chlorine-uv combined oxidation for removing algae-caused noxious substance, and variable control method of chlorine dosage and uv dose using the same |
| CN104829466A (en) * | 2015-05-11 | 2015-08-12 | 泰山医学院 | Method of synthesizing 3-methylamino-1,2-propylene glycol by pipeline reactor |
| CN104844463A (en) * | 2015-05-19 | 2015-08-19 | 泰山医学院 | Green synthetic method of high-purity 3-methylamino-1,2-propandiol |
| CN105254521A (en) * | 2015-10-27 | 2016-01-20 | 遵义医学院 | Preparation technology of iopromide intermediate |
Non-Patent Citations (4)
| Title |
|---|
| KAZUKI TAINAKA 等: "Whole-Body Imaging with Single-Cell Resolution by Tissue Decolorization", 《CELL》 * |
| 张中法 等: "3-甲胺基-1,2-丙二醇生产新工艺", 《贵州化工》 * |
| 张恭孝 等: "固体碱催化合成3-甲胺基-1，2-丙二醇", 《精细化工》 * |
| 王枫: "N,N-(R1,R2)-3-氨基-1,2-丙二醇化合物的催化合成研究", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113030353A (en) * | 2019-12-25 | 2021-06-25 | 上海奥博生物医药技术有限公司 | Method for measuring content of (S) -1, 2-propylene glycol chiral isomer |
| CN112782304A (en) * | 2020-12-28 | 2021-05-11 | 广东肇庆星湖生物科技股份有限公司 | Capillary gas chromatography analysis method of dimethylamino-2-propanol |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105758970B (en) | 2018-05-15 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105891375A (en) | Method using ultra-performance convergence chromatography to fast detect chiral ethyl lactate in Baijiu | |
| CN113466353B (en) | Method for detecting 6-chloro-2-hexanone related substances | |
| CN105486794A (en) | Method for detecting banned dye in printing ink | |
| CN105758970A (en) | Method for detecting purity of 3-methylamino-1,2-propandiol by gas chromatography | |
| CN107957467A (en) | A kind of method of lysophosphatidyl choline in separation determination pharmaceutical preparation | |
| CN110780002B (en) | High-efficiency low-cost detection method for quantifying essential oil components | |
| CN108287206A (en) | Barbiturate quantitative detecting method and application in a kind of hair | |
| CN110895264A (en) | Method for determining ethyl bromide in tenofovir alafenamide | |
| CN116008430A (en) | Gas chromatography method for determining ethanol and propylene glycol in minoxidil external solution | |
| CN108872416A (en) | A kind of method of simultaneous quantitative detection erucyl amide and ethylene bis stearamide | |
| CN111426760B (en) | Method for determining genotoxic impurities in doxofylline raw material medicine | |
| CN113030328B (en) | Method for detecting genotoxic impurities in ivabradine hydrochloride | |
| CN108387653A (en) | A kind of method of ethanol content in measurement industrial methanol | |
| CN114942280A (en) | Method for content determination and mass spectrum confirmation of 12 hair dyes in cosmetics | |
| CN106018595A (en) | Method for detecting purity of 3-methylamino-1,2-propylene glycol with capillary column method | |
| CN107271586A (en) | The analysis method of residual solvent residual quantity in a kind of Rivaroxaban intermediate | |
| CN113777204B (en) | Detection method of p-hydroxyacetophenone related substances | |
| CN115343399B (en) | Method for detecting residual solvent of N-alkyl pyrrolidone in bulk drug | |
| CN106526050B (en) | The content assaying method of phenol in a kind of iron dextran injection | |
| CN114200067B (en) | High performance liquid chromatography analysis method for 6-bromo-3-hydroxy pyrazine-2-carboxamide and impurities | |
| CN115015457B (en) | Method for analyzing bromoacetic acid impurity in selapage by high performance liquid chromatography | |
| CN113376290B (en) | Vitamin D detection by gas chromatography 2 Method for residual organic solvent in water | |
| CN109507327B (en) | Quantitative determination of TNT content by GC-AED independent calibration curve method (CIC method) | |
| CN111060629B (en) | Method for detecting related substances of lifusy | |
| CN116400002A (en) | N, N-dimethylethanolamine detection method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20180515 Termination date: 20190517 |