CN105527365A - Method for analyzing alpha-fluoromethyl acrylate and related substances - Google Patents
Method for analyzing alpha-fluoromethyl acrylate and related substances Download PDFInfo
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Abstract
The invention discloses a method for analyzing alpha-fluoromethyl acrylate and related substances. Chromatographic conditions are as follows: a polar capillary chromatographic column is employed as a chromatographic column; a temperature control mode is programmed heating, a split mode is employed for sample introduction and nitrogen is used as carrying gas; a flame ionization detector is used as a detector; and alpha-fluoromethyl acrylate and a reference substance are prepared from a first solvent and a second solvent, wherein the first solvent is acetone and/or acetonitrile and the second solvent is a derivatization reagent. Solutions of alpha-fluoromethyl acrylate and the reference substance are placed in a sample injector; and after balancing, a sample or reference substance is injected into a gas chromatograph so as to accomplish determination of alpha-fluoromethyl acrylate and the related substances. With the method, alpha-fluoromethyl acrylate and impurities produced during synthesis of alpha-fluoromethyl acrylate can be rapidly and highly-efficiently separated under same chromatographic conditions, so synthesis reaction process and product quality are effectively controlled. The detection method is convenient to operate, has high sensitivity and good accuracy and can comprehensively and effectively control product quality.
Description
Technical field
The invention belongs to Pharmaceutical Analysis technical field, specifically, the present invention relates to a kind of method analyzing alpha-fluoro methyl acrylate and related substance thereof.
Background technology
In recent years, the application in medicine and materials industry of alpha-fluoro methyl acrylate and analog thereof is more and more, and demand is also thereupon increasing.Be particularly that the polymkeric substance that raw material makes is applied very extensive in information industry with acrylate; In field of medicaments, by alpha-fluoro methyl acrylate be the polymkeric substance prepared of raw material after being combined with some active high medicines, can new drug be made, enter in human body as Transfer Medium, potassium unnecessary for some human bodies, sodion etc. are excreted.
Wherein, any one separately for being selected from following each group of R, X: C
1-C
3alkyl, X is halogen group.
Alpha-fluoro methyl acrylate is as the one in compound shown in formula I, synthetic route can be adopted: methylfluoracetate+dimethyl oxalate → enol sodium salt or sylvite → alpha-fluoro methyl acrylate, but, accessory substance easily residual in the product and impurity comprise: methyl alcohol (MeOH), t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2,6-tert-butyl-4-methyl-Phenols (BHT), methylfluoracetate (MFAc), toluene (Toluene).On the other hand, out of order, be not easy to be separated, the production cycle can extend the enol sodium salt/sylvite intermediate generated in view of alkane reaction, causes production cost and cost of labor to increase, the therefore very not applicable industrialized production of this synthetic route.Although report: enol sodium salt/sylvite intermediate can be separated, directly carry out second step reaction, but due to the by-product carbinol that must exist in reaction, enol sodium salt/sylvite generation reversible reaction can be caused, operator is caused to think the unclosed illusion of reaction, affect process, thus cause second step reaction impurities to increase, product yield is low and process costs is high.Therefore strict control is carried out to building-up process and especially show important, with full-scope safeguards product quality and production safety, and effectively reduce production cost.
At present, the method analyzing alpha-fluoro methyl acrylate and related substance thereof still haves much room for improvement.
Summary of the invention
The present invention is intended to solve one of technical matters in correlation technique at least to a certain extent.For this reason, one object of the present invention is to propose a kind of method analyzing alpha-fluoro methyl acrylate and related substance thereof, and the method can accurately control first step reaction mass, Simultaneously test alpha-fluoro methyl acrylate content.[methyl alcohol (MeOH), t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2 is comprised by the analysis major product of quick separating under same chromatographic condition and related substance, 6-tert-butyl-4-methyl-Phenol (BHT), methylfluoracetate (MFAc), toluene, enol sodium salt or sylvite], realize the quality control of alpha-fluoro methyl acrylate, meet the industrialized production of product.
In one aspect of the invention, the invention provides a kind of method analyzing alpha-fluoro methyl acrylate and related substance thereof.It is characterized in that:
(1) chromatographic condition:
Chromatographic column adopts polarity capillary chromatographic column;
Temperature control mode is temperature programme, sample introduction shunt mode, and carrier gas is nitrogen;
Detecting device is flame ionization ditector;
(2) preparation of sample solution: alpha-fluoro methyl acrylate and reference substance are separately prepared with the mixed solvent of the first solvent and the second solvent;
Wherein, described first solvent is acetone and/or acetonitrile, and described second solvent is derivatization reagent;
(3) measure: the alpha-fluoro methyl acrylate solution obtain preparation in step (2) and reference substance solution are placed in injector, after balance, are injected into gas chromatograph, complete the mensuration of alpha-fluoro methyl acrylate and related substance thereof.
Alpha-fluoro methyl acrylate and reference substance the first solvent and derivatization reagent preparation, the trifluoroacetic acid in derivatization reagent and sample quality number percent are 3 ~ 45%.
According to the analysis alpha-fluoro methyl acrylate of the embodiment of the present invention and the method for related substance thereof, can effectively to methyl alcohol in product (MeOH), t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2,6-tert-butyl-4-methyl-Phenol (BHT), methylfluoracetate (MFAc), toluene (Toluene) and enol sodium salt or sylvite detect, and its testing result has significant sensitivity, stability and repeatability.By adding derivatization reagent in the sample preparation stage, can can't make in detection the enol sodium salt at peak or sylvite need not separate just can Accurate Determining Fluoride for Raw Material methyl acetate and enol sodium salt or sylvite, analytical approach accuracy of the present invention is strong, easy and simple to handle, can effective control for product quality.
In addition, according to the analysis alpha-fluoro methyl acrylate of the embodiment of the present invention and the method for related substance thereof, following additional technical feature can also be had:
In some embodiments of the invention, carry out temperature programme to chromatographic column: during 0 ~ 10min, column temperature remains a steady temperature between 35 ~ 45 DEG C, rises to 50 ~ 60 DEG C afterwards with 2 ~ 8 DEG C/min, rise to 200 ~ 250 DEG C with 20 ~ 30 DEG C/min again, keep 3 ~ 7min.Thus can effectively separating alpha-fluoromethacrylate and related substance.
In some embodiments of the invention, the split ratio of described shunt mode is 30:1 ~ 60:1, preferred 50:1.Thus, detection sensitivity can be significantly improved.
In some embodiments of the invention, described derivatization reagent is the mixed solvent of organic acid and organic reagent.Thus can abundant sample dissolution, and improve peak type.
In some embodiments of the invention, described organic acid is trifluoroacetic acid.The damage to instrument can be reduced thus, improve the degree of separation of alpha-fluoro methyl acrylate and related substance simultaneously further.
In some embodiments of the invention, described organic reagent is acetone and/or acetonitrile.Thus can abundant sample dissolution and do not disturb the detection of impurity.
In some embodiments of the invention, the mass ratio of described organic acid and described trifluoroacetic acid is 1-3g:50-200mg.Thus can abundant sample dissolution and do not disturb the detection of impurity.
In some embodiments of the invention, the number percent of described organic acid and sample quality is 3 ~ 45%.It is thorough that acid addition can make enol sodium salt or sylvite dissociate not, and testing result is inaccurate, and addition is excessive, there will be impurity peaks, interference measurement, and peak type is bad, also may damage instrument before enol sodium salt or sylvite free state peak.According to a particular embodiment of the invention, the sample in the number percent of above-mentioned organic acid and sample quality refers to alpha-fluoro methyl acrylate or reference substance.
In some embodiments of the invention, the temperature of described detecting device is 230 ~ 260 degrees Celsius, preferably 250 degrees Celsius.Thus, the degree of separation of each component in alpha-fluoro methyl acrylate can be improved further.
In some embodiments of the invention, in described chromatographic column, the particle diameter of filler is 0.1-0.5 μm.Thus, the degree of separation of each component in alpha-fluoro methyl acrylate can be improved further.
In some embodiments of the invention, described analytical approach adopts 30m × 0.32mm, and the DB-wax chromatographic column of 0.25 μm, carries out temperature programme, and condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Wherein, injector temperature is 230 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1ml/min, and sampling volume is 1 μ L, split ratio 50:1.
Thus, detect while effectively can realizing alpha-fluoro methyl acrylate and methylfluoracetate, enol sodium salt or sylvite.
In some embodiments of the invention, described analytical approach adopts 30m × 0.32mm, and the DB-wax chromatographic column of 0.25 μm, carries out temperature programme, and condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 200 | 6 | 23.6 |
Wherein, injector temperature is 240 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1ml/min, and sampling volume is 1 μ L, split ratio 50:1.
Thus, detect while effectively can realizing alpha-fluoro methyl acrylate (MFA) and methylfluoracetate (MFAc), methyl alcohol (MeOH), t-butyl methyl ether (MtBE), dimethyl carbonate (DMC), 2,6-tert-butyl-4-methyl-Phenols (BHT), toluene (Toluene).
In some embodiments of the invention, impurity location solution comprises methylfluoracetate (MFAc), dimethyl carbonate (DMC), t-butyl methyl ether (MtBE), 2 respectively, 6-tert-butyl-4-methyl-Phenol (BHT), toluene (Toluene), methyl alcohol (MeOH), wherein, BHT concentration is 0.08mg/mL, and other concentration is 0.4mg/mL.Thus, reducing sample size while as far as possible, response can be made to meet the needs of mensuration, avoid continuous high-concentration sample introduction, extend the serviceable life of chromatographic column.And under this concentration, principal ingredient alpha-fluoro methyl acrylate is separated completely with between other peaks.
The wash-out separating effect of the inventive method is better, and 6 impurity in sample can be made effectively to be separated and quantitatively to detect.Detection time only needs 24min.Weight per unit length limit concentration is 24 μ g/mL, can fast, accurately, reliable separating alpha-fluoromethacrylate and adjacent impurity.
Additional aspect of the present invention and advantage will part provide in the following description, and part will become obvious from the following description, or be recognized by practice of the present invention.
Accompanying drawing explanation
Fig. 1 shows according to embodiments of the invention 1, the gas chromatogram of gained alpha-fluoro methyl acrylate and impurity location;
Fig. 2 shows according to embodiments of the invention 2, the gas chromatogram of gained alpha-fluoro methyl acrylate and impurity;
Fig. 3 shows according to embodiments of the invention 3, the gas chromatogram of gained alpha-fluoro methyl acrylate reactant liquor;
Fig. 4 shows according to embodiments of the invention 4, the gas chromatogram of gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity;
Fig. 5 shows according to embodiments of the invention 4, the gas chromatogram of gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity;
Fig. 6 shows according to comparative example 1 of the present invention, the gas chromatogram of gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity.
Fig. 7 shows according to comparative example 2 of the present invention, the gas chromatogram of gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity.
Embodiment
Embodiments of the invention are described below in detail.Embodiment described below is exemplary, only for explaining the present invention, and can not be interpreted as limitation of the present invention.Unreceipted concrete technology or condition in embodiment, according to the technology described by the document in this area or condition or carry out according to product description.Agents useful for same or the unreceipted production firm person of instrument, being can by the conventional products of commercial acquisition.
Alpha-fluoro methyl acrylate used in the embodiment of the present invention and enol sodium salt or sylvite intermediate are applicant's self-control.
Alpha-fluoro methyl acrylate and enol sodium salt obtain through methylfluoracetate+dimethyl oxalate → enol sodium salt or sylvite → alpha-fluoro methyl acrylate synthesis.
Embodiment 1
Instrument: Agilent7890A gas chromatograph, fid detector
Chromatographic column: DB-wax (30m × 0.32mm × 0.25 μm);
Temperature programme condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 200 | 6 | 23.6 |
Flow velocity: 1.0mL/min
Detector temperature: 250 DEG C
Injector temperature: 240 DEG C
Sampling volume: 1 μ L
Split ratio: 50:1
Thinning agent: acetonitrile
Derivatization reagent: add 60mg trifluoroacetic acid in 2g acetonitrile
Working time: 23.6min
Experimental procedure:
BHT reference substance stock solution: BHT reference substance is about 80mg, accurately weighed, puts in 50mL volumetric flask, adds thinning agent and dissolves and be diluted to scale, shake up.
Sample and each component reference substance solution: take alpha-fluoro methyl acrylate reference substance and be about 80mg, take each about 40mg of MeOH, Toluene, MtBE, DMC, MFAc reference substance, accurately weighed, put in 100mL volumetric flask, precision pipettes 5mLBHT reference substance stock solution again, is set up and states in 100mL volumetric flask, adds 1mL derivatization reagent, dissolve with thinning agent again and be diluted to scale, shaking up.
Quantitative limit solution: precision pipettes 5mLBHT reference substance stock solution, is placed in 100mL volumetric flask and dilutes constant volume, then precision pipettes 1mLBHT solution, put in 10mL volumetric flask, add thinning agent and be diluted to scale, shake up (0.008mg/mL), be equivalent to 40ppm.
Experimental result:
As shown in Figure 1, its data are in table 1 for the gas chromatogram of alpha-fluoro methyl acrylate and impurity location.
Table 1 alpha-fluoro methyl acrylate and impurity positioning result
| Analyze thing | Retention time | Degree of separation |
| T-butyl methyl ether (MtBE) | 3.63min | 78.74 |
| Methyl alcohol (MeOH) | 7.56min | 33.57 |
| Dimethyl carbonate (DMC) | 11.28min | 4.06 |
| Alpha-fluoro methyl acrylate (MFA) | 11.84min | - |
| Toluene (Toluene) | 13.06min | 11.23 |
| 2-methylfluoracetate (MFAc) | 14.16min | 23.25 |
| 2,6-tert-butyl-4-methyl-Phenol (BHT) | 21.15min | 85.72 |
Conclusion: under this chromatographic condition, alpha-fluoro methyl acrylate can be issued to good being separated at same chromatographic condition with 6 impurity, sample result also shows that BHT impurity is when content is 40ppm, and carrying out gas chromatographic analysis can do qualitative analysis, is quantitatively limited to 40ppm.
Embodiment 2
Instrument: Agilent7890A gas chromatograph, fid detector
Chromatographic column: DB-wax (30m × 0.32mm × 0.25 μm);
Temperature programme condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 200 | 6 | 23.6 |
Flow velocity: 1.0mL/min
Detector temperature: 250 DEG C
Injector temperature: 240 DEG C
Sampling volume: 1 μ L
Split ratio: 50:1
Thinning agent: acetonitrile
Derivatization reagent: add 60mg trifluoroacetic acid in 2g acetonitrile
Working time: 23.6 minutes
Experimental procedure:
Impurity content reference substance solution: get MFA reference substance and be about 800mg, accurately weighed, put and added in the l0mL volumetric flask of 5mL thinning agent and 1mL derivatization reagent, add thinning agent and dissolve and be diluted to scale, shake up (80mg/mL).Precision pipettes 1mL and puts in 200mL volumetric flask, adds thinning agent and is diluted to scale, shakes up (0.4mg/mL).
Sample solution: get MFA sample and be about 800mg, accurately weighed, put and added in the 10mL volumetric flask of 5mL thinning agent and 1mL derivatization reagent, add thinning agent and dissolve and be diluted to scale, shake up (80mg/mL).
Quantitative limit solution: precision pipettes 3mL impurity content reference substance solution, puts in 50mL volumetric flask, adds thinning agent and is diluted to scale, shakes up (24 μ g/mL), is equivalent to the content of 0.03%.
Experimental result:
As shown in Figure 2, its data are in table 2 for the gas chromatogram of alpha-fluoro methyl acrylate and impurity.
Table 2 alpha-fluoro methyl acrylate and defects inspecting result
| Analyze thing | Retention time | RRF | Content |
| T-butyl methyl ether (MtBE) | 3.63min | 0.53 | 0.02％ |
| Methyl alcohol (MeOH) | 7.56min | 1.10 | 0.24％ |
| Dimethyl carbonate (DMC) | 11.28min | 1.98 | 0.10％ |
| Alpha-fluoro methyl acrylate (MFA) | 11.84min | 1.00 | 98.30％ |
| Toluene (Toluene) | 13.06min | 0.35 | 0.06％ |
| 2-methylfluoracetate (MFAc) | 14.16min | 1.45 | 0.38％ |
| 2,6-tert-butyl-4-methyl-Phenol (BHT) | 21.15min | 0.35 | 280ppm |
Conclusion: under this chromatographic condition, alpha-fluoro methyl acrylate can be issued to good being separated at same chromatographic condition with 6 impurity.When major component alpha-fluoro methyl acrylate concentration is 24 μ g/mL, carrying out gas chromatographic analysis can do qualitative analysis, is quantitatively limited to the content of 0.03%.Result shows that the method can be used for the quality testing of alpha-fluoro methyl acrylate.
Embodiment 3
Instrument: Agilent7890A gas chromatograph, fid detector
Chromatographic column: DB-wax (30m × 0.32mm × 0.25 μm);
Temperature programme condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity: 1.0mL/min
Detector temperature: 250 DEG C
Injector temperature: 230 DEG C
Sampling volume: 1 μ L
Split ratio: 50:1
Thinning agent: acetone
Derivatization reagent: add 100mg trifluoroacetic acid in 2g acetone
Working time: 23.8min
Experimental procedure: precision takes MFA reactant liquor and is about 200mg, adds 1mL derivatization reagent and 1mL thinning agent, shakes up, and filters, to obtain final product.
Conclusion: under this chromatographic condition, as shown in Figure 3, wherein methylfluoracetate goes out peak 11.304min to the gas chromatogram of gained alpha-fluoro methyl acrylate reactant liquor, and enol sodium salt free state goes out peak 18.775min, and MFA goes out peak 7.449min.Chromatogram shows that in reactant liquor, methylfluoracetate can be issued to good being separated with main composition MFA at same chromatographic condition with enol sodium salt free state.Result shows that the method can be used for reaction monitoring and the quality testing of MFA.
Embodiment 4
Instrument: Agilent7890A gas chromatograph, fid detector
Chromatographic column: DB-wax (30m × 0.32mm × 0.25 μm);
Temperature programme condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity: 1.0mL/min
Detector temperature: 250 DEG C
Injector temperature: 230 DEG C
Sampling volume: 1 μ L
Split ratio: 50:1
Thinning agent: acetone
Derivatization reagent: add 180mg trifluoroacetic acid in 2g acetone
Working time: 23.8min
Experimental procedure: precision takes enol sodium salt reactant liquor and is about 200mg, adds 1mL derivatization reagent and 0.5mL thinning agent, shakes up, and filters, to obtain final product.
Conclusion: under this chromatographic condition, the gas chromatogram of gained alpha-fluoro methyl acrylate intermediate enol sodium salt and impurity as shown in Figure 4 and Figure 5.Wherein methylfluoracetate goes out peak 11.363min, and enol sodium salt free state goes out peak 18.742min.
Chromatogram 4 shows that in reactant liquor, enol sodium salt free state can go out peak, and methylfluoracetate can be issued to good being separated with enol sodium salt free state at same chromatographic condition.Result shows that the method can be used for reaction monitoring and the quality testing of enol sodium salt.What chromatogram 5 showed is that a trifluoroacetic acid adds excessive sample drawing, and show that trifluoroacetic acid needs to control addition, there will be assorted peak before too much main peak, impact detects.
Comparative example 1
Instrument: Agilent7890A gas chromatograph, fid detector
Chromatographic column: DB-wax (30m × 0.32mm × 0.25 μm);
Temperature programme condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) 7--> |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity: 1.0mL/min
Detector temperature: 250 DEG C
Injector temperature: 230 DEG C
Sampling volume: 1 μ L
Split ratio: 50:1
Thinning agent: acetone
Derivatization reagent: add 200mg oxalic acid in 2g acetone
Working time: 23.8min
Experimental procedure: precision takes enol sodium salt reactant liquor and is about 180mg, adds 1mL derivatization reagent and 0.5mL thinning agent, shakes up, and filters, to obtain final product.
Conclusion: survey external standard free state product 12.5% with the oxalic acid enol sodium salt that dissociates, methylfluoracetate has 28%, and may be that oxalic acid is not acid, not exclusively free, method be inaccurate, poor repeatability.
Comparative example 2
Instrument: Agilent7890A gas chromatograph, fid detector
Chromatographic column: DB-wax (30m × 0.32mm × 0.25 μm);
Temperature programme condition is:
| Heating rate (DEG C/min) | Temperature (DEG C) | Retention time (min) | Working time (min) |
| 40 | 8 | 8 | |
| 5 | 60 | 0 | 12 |
| 25 | 230 | 5 | 23.8 |
Flow velocity: 1.0mL/min
Detector temperature: 250 DEG C
Injector temperature: 230 DEG C
Sampling volume: 1 μ L
Split ratio: 50:1
Thinning agent: acetone
Derivatization reagent: add 150mg hydrochloric acid in 2g acetone
Working time: 23.8min
Experimental procedure: precision takes enol sodium salt reactant liquor and is about 180mg, adds 1mL derivatization reagent and 0.5mL thinning agent, shakes up, and filters, to obtain final product.
Conclusion: survey external standard free state product there is no with the oxalic acid enol sodium salt that dissociates, methylfluoracetate has 7.16%, have more the impurity peaks that 19.16min and 21.25min two is larger, may be that hydrochloric acid acidity is too strong, cause occurring new impurity, method is inaccurate, and the too strong reagent of acidity also can have certain infringement to instrument.
In describing the invention, it is to be appreciated that term " first ", " second " only for describing object, and can not be interpreted as instruction or hint relative importance or the implicit quantity indicating indicated technical characteristic.Thus, be limited with " first ", the feature of " second " can express or impliedly comprise one or more these features.In describing the invention, the implication of " multiple " is two or more, unless otherwise expressly limited specifically.
In the description of this instructions, specific features, structure, material or feature that the description of reference term " embodiment ", " some embodiments ", " example ", " concrete example " or " some examples " etc. means to describe in conjunction with this embodiment or example are contained at least one embodiment of the present invention or example.In this manual, to the schematic representation of above-mentioned term not must for be identical embodiment or example.And the specific features of description, structure, material or feature can combine in one or more embodiment in office or example in an appropriate manner.In addition, when not conflicting, the feature of the different embodiment described in this instructions or example and different embodiment or example can carry out combining and combining by those skilled in the art.
Although illustrate and describe embodiments of the invention above, be understandable that, above-described embodiment is exemplary, can not be interpreted as limitation of the present invention, and those of ordinary skill in the art can change above-described embodiment within the scope of the invention, revises, replace and modification.
Claims (10)
1. analyze a method for alpha-fluoro methyl acrylate and related substance thereof, it is characterized in that, described method comprises the steps:
(1) chromatographic condition:
Chromatographic column adopts polarity capillary chromatographic column;
Temperature control mode is temperature programme, sample introduction shunt mode, and carrier gas is nitrogen;
Detecting device is flame ionization ditector;
(2) preparation of sample solution: alpha-fluoro methyl acrylate and reference substance are separately prepared with the mixed solvent of the first solvent and the second solvent;
Wherein, described first solvent is acetone and/or acetonitrile, and described second solvent is derivatization reagent;
(3) measure: the alpha-fluoro methyl acrylate solution obtain preparation in step (2) and reference substance solution are placed in injector, after balance, are injected into gas chromatograph, complete the mensuration of alpha-fluoro methyl acrylate and related substance thereof.
2. method according to claim 1, it is characterized in that, temperature programme is carried out to chromatographic column: during 0 ~ 10min, column temperature remains a steady temperature between 35 ~ 45 DEG C, 50 ~ 60 DEG C are risen to afterwards with 2 ~ 8 DEG C/min, rise to 200 ~ 250 DEG C with 20 ~ 30 DEG C/min again, keep 3 ~ 7min.
3. method according to claim 1, is characterized in that, sample introduction split ratio is 30:1 ~ 60:1, preferred 50:1.
4. method according to claim 1, is characterized in that, described derivatization reagent is the mixed solvent of organic acid and organic reagent.
5. method according to claim 4, is characterized in that, described organic reagent is acetone and/or acetonitrile,
Optionally, described organic acid is trifluoroacetic acid.
6. method according to claim 5, is characterized in that, the mass ratio of described organic acid and described trifluoroacetic acid is 1-3g:50-200mg.
7. method according to claim 6, is characterized in that, the trifluoroacetic acid in described derivatization reagent and sample quality number percent are 3 ~ 45%.
8. method according to claim 1, is characterized in that, the temperature of described detecting device is 230 ~ 260 degrees Celsius, preferably 250 degrees Celsius.
9. method according to claim 1, is characterized in that, described analysis adopts 30m × 0.32mm, and the DB-wax chromatographic column of 0.25 μm, carries out temperature programme, and condition is:
Wherein, injector temperature is 230 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1mL/min, and sampling volume is 1 μ L, split ratio 50:1.
10. method according to claim 1, is characterized in that, described analysis adopts 30m × 0.32mm, and the DB-wax chromatographic column of 0.25 μm, carries out temperature programme, and condition is:
Wherein, injector temperature is 240 degrees Celsius, and detector temperature is 250 degrees Celsius, and flow velocity is 1mL/min, and sampling volume is 1 μ L, split ratio 50:1.
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