CN112285227A - Gas chromatography analysis method for hexafluoroacetone in mifepristone - Google Patents
Gas chromatography analysis method for hexafluoroacetone in mifepristone Download PDFInfo
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- CN112285227A CN112285227A CN202011112222.4A CN202011112222A CN112285227A CN 112285227 A CN112285227 A CN 112285227A CN 202011112222 A CN202011112222 A CN 202011112222A CN 112285227 A CN112285227 A CN 112285227A
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- mifepristone
- hexafluoroacetone
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- VKHAHZOOUSRJNA-GCNJZUOMSA-N mifepristone Chemical compound C1([C@@H]2C3=C4CCC(=O)C=C4CC[C@H]3[C@@H]3CC[C@@]([C@]3(C2)C)(O)C#CC)=CC=C(N(C)C)C=C1 VKHAHZOOUSRJNA-GCNJZUOMSA-N 0.000 title claims abstract description 37
- 229960003248 mifepristone Drugs 0.000 title claims abstract description 37
- VBZWSGALLODQNC-UHFFFAOYSA-N hexafluoroacetone Chemical compound FC(F)(F)C(=O)C(F)(F)F VBZWSGALLODQNC-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000004458 analytical method Methods 0.000 title claims abstract description 13
- 238000004817 gas chromatography Methods 0.000 title claims abstract description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000002904 solvent Substances 0.000 claims abstract description 10
- 239000004205 dimethyl polysiloxane Substances 0.000 claims abstract description 8
- 235000013870 dimethyl polysiloxane Nutrition 0.000 claims abstract description 8
- 229920000435 poly(dimethylsiloxane) Polymers 0.000 claims abstract description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 5
- 230000005264 electron capture Effects 0.000 claims abstract description 5
- 239000012159 carrier gas Substances 0.000 claims abstract description 4
- 239000000243 solution Substances 0.000 claims description 12
- 238000002347 injection Methods 0.000 claims description 10
- 239000007924 injection Substances 0.000 claims description 10
- 239000000523 sample Substances 0.000 claims description 10
- 239000007789 gas Substances 0.000 claims description 7
- 238000007865 diluting Methods 0.000 claims description 6
- 239000012488 sample solution Substances 0.000 claims description 6
- 238000012360 testing method Methods 0.000 claims description 6
- 238000005303 weighing Methods 0.000 claims description 6
- 238000001514 detection method Methods 0.000 claims description 4
- 229910001873 dinitrogen Inorganic materials 0.000 claims description 3
- 238000010812 external standard method Methods 0.000 claims description 3
- 238000002309 gasification Methods 0.000 claims description 3
- 238000010438 heat treatment Methods 0.000 claims description 2
- 238000003556 assay Methods 0.000 claims 3
- 238000000034 method Methods 0.000 abstract description 7
- 239000012535 impurity Substances 0.000 abstract description 4
- 238000000926 separation method Methods 0.000 abstract description 4
- 238000005220 pharmaceutical analysis Methods 0.000 abstract description 2
- 229910052757 nitrogen Inorganic materials 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- SNZAEUWCEHDROX-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-one;trihydrate Chemical compound O.O.O.FC(F)(F)C(=O)C(F)(F)F SNZAEUWCEHDROX-UHFFFAOYSA-N 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 230000001939 inductive effect Effects 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- 230000035935 pregnancy Effects 0.000 description 2
- 206010006784 Burning sensation Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 208000001951 Fetal Death Diseases 0.000 description 1
- 206010055690 Foetal death Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 201000008197 Laryngitis Diseases 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 206010035664 Pneumonia Diseases 0.000 description 1
- 229940123788 Progesterone receptor antagonist Drugs 0.000 description 1
- 206010037423 Pulmonary oedema Diseases 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 208000005392 Spasm Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- 210000000621 bronchi Anatomy 0.000 description 1
- 210000003679 cervix uteri Anatomy 0.000 description 1
- 230000000916 dilatatory effect Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 231100000479 fetal death Toxicity 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000000622 irritating effect Effects 0.000 description 1
- 230000005906 menstruation Effects 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 208000005333 pulmonary edema Diseases 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 210000002345 respiratory system Anatomy 0.000 description 1
- 208000013220 shortness of breath Diseases 0.000 description 1
- 210000003491 skin Anatomy 0.000 description 1
- 150000003431 steroids Chemical group 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 238000012418 validation experiment Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
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Classifications
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- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
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- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Sampling And Sample Adjustment (AREA)
Abstract
The invention belongs to the technical field of pharmaceutical analysis, and relates to a gas chromatography analysis method of hexafluoroacetone in mifepristone. The invention adopts gas chromatography, a chromatographic column is 100 percent dimethyl polysiloxane with the specification of 30m multiplied by 0.32mm multiplied by 0.25um, the initial temperature of the column temperature is 40 ℃, the gradient temperature is increased to 250 ℃, a detector is an electron capture detector, carrier gas is nitrogen, and methanol is a special solvent. The method is relatively simple, high in accuracy, good in separation degree from other impurities and wide in application range.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical analysis, and relates to a gas chromatography analysis method of hexafluoroacetone in mifepristone.
Background
Mifepristone has a steroid structure, is a first progesterone receptor antagonist, has the effects of softening and dilating cervix, is clinically used for resisting early pregnancy, inducing menstruation to stop pregnancy, inducing labor in uterus during fetal death and the like, and has important quality requirements due to special use population.
The synthesis process of mifepristone is more, but the most economic synthesis process at present uses hexafluoroacetone trihydrate. However, hexafluoroacetone trihydrate may remain as an unknown toxic solvent, has a strong irritating effect on eyes, skin, mucous membranes and respiratory tract, and may be fatal by spasm and edema of throat and bronchi, chemical pneumonia and pulmonary edema after inhalation, and has the symptoms of burning sensation, cough, wheezing, laryngitis, shortness of breath, headache, nausea and vomiting. Therefore, the amount of hexafluoroacetone as an impurity in the synthesis of mifepristone is strictly controlled to ensure the quality of mifepristone medicine.
However, under the current policy environment that the quality of medicines is increasingly strict, no medicine standard which lists hexafluoroacetone as a mifepristone control index exists, and no suitable detection and control method for hexafluoroacetone in mifepristone is reported.
Therefore, the simple and accurate hexafluoroacetone analysis method can be provided, and the method has important significance for ensuring the quality of mifepristone products and the life safety of users.
Disclosure of Invention
In order to solve the problems, the invention provides a high-accuracy gas chromatography analysis method for hexafluoroacetone in mifepristone.
The invention relates to a high-accuracy gas chromatographic analysis method for hexafluoroacetone in mifepristone, which adopts methanol as a special solvent and an electronic capture detector.
Furthermore, the gas chromatographic analysis method of hexafluoroacetone in mifepristone adopts a 100% dimethyl polysiloxane gas chromatographic column with the specification of 30m multiplied by 0.32mm multiplied by 0.25 mu m, adopts a gradient heating detection method, sets 40 ℃ as an initial temperature, keeps the temperature for 4-8 minutes, and then raises the temperature to 250 ℃ at the rate of 21 ℃ per minute and keeps the temperature for 4-8 minutes.
The analysis method comprises the following specific steps:
1) taking a proper amount of hexafluoroacetone, precisely weighing, taking methanol as a solvent, dissolving and diluting the hexafluoroacetone step by step to prepare a solution of 10 mu g/ml, and obtaining a hexafluoroacetone solution;
2) taking a proper amount of mifepristone, precisely weighing, taking methanol as a solvent, dissolving and diluting to prepare a solution containing 10mg/ml of mifepristone to obtain a mifepristone test sample solution;
3) agilent7890B gas chromatograph, chromatographic column is 100% dimethyl polysiloxane with specification of 30m × 0.32mm × 0.25 μm; the initial temperature of the column temperature is 40 ℃, the column temperature is kept for 4 to 8 minutes, and then the column temperature is increased to 250 ℃ at the rate of 21 ℃ per minute, and the column temperature is kept for 4 to 8 minutes; the sample injection mode is direct sample injection, and the sample injection volume is 1 mu l; the detector is an electron capture detector, and the temperature of the detector is 300 ℃; the temperature of the gasification chamber is 250 ℃; the carrier gas is nitrogen gas, and the concentration is 60 ml/min;
4) and respectively adding a hexafluoroacetone solution and a mifepristone test sample solution, and calculating the content of hexafluoroacetone in mifepristone by adopting an external standard method.
The invention provides a quality control method of hexafluoroacetone in mifepristone for the first time. Meanwhile, the gas chromatography analysis method for hexafluoroacetone in mifepristone is relatively simple, high in accuracy, good in separation degree with other impurities and wide in application range.
Drawings
FIG. 1 is a gas chromatogram of a mixed solution of mifepristone and hexafluoroacetone in a validation experiment of example 1.
Detailed Description
The present invention will be further illustrated by the following specific examples, but the scope of the present invention is not limited thereto.
Example 1
A high-accuracy gas chromatography analysis method for hexafluoroacetone in mifepristone comprises the following specific steps: 1) taking a proper amount of hexafluoroacetone, precisely weighing, taking methanol as a solvent, dissolving and diluting the hexafluoroacetone step by step to prepare a solution of 10 mu g/ml, and obtaining a hexafluoroacetone solution; 2) taking a proper amount of mifepristone, precisely weighing, taking methanol as a solvent, dissolving and diluting to prepare a solution containing 10mg/ml of mifepristone to obtain a mifepristone test sample solution; 3) agilent7890B gas chromatograph, chromatographic column is 100% dimethyl polysiloxane with specification of 30m × 0.32mm × 0.25 μm; the initial temperature of the column temperature is 40 ℃, the column temperature is kept for 6 minutes, and then the column temperature is increased to 250 ℃ at the rate of 21 ℃ per minute, and the column temperature is kept for 5 minutes; the sample injection mode is direct sample injection, and the sample injection volume is 1 mu l; the detector is an electron capture detector, and the temperature of the detector is 300 ℃; the temperature of the gasification chamber is 250 ℃; the carrier gas is nitrogen gas, and the concentration is 60 ml/min; 4) and respectively adding a hexafluoroacetone solution and a mifepristone test sample solution, and calculating the content of hexafluoroacetone in mifepristone by adopting an external standard method.
And (3) verification experiment:
hexafluoroacetone is doped into mifepristone to prepare a mixed solution, the concentration of the mifepristone is 10mg/ml, the concentration of the hexafluoroacetone is 10 mu g/ml, the detection is carried out according to the analysis method, the sample injection volume is 1 mu l, the result is shown in figure 1, and the separation degree of each component is good. The gas chromatography analysis method for hexafluoroacetone in mifepristone is relatively simple, high in accuracy, good in separation degree from other impurities and wide in application range.
Claims (4)
1. A gas chromatography analysis method of hexafluoroacetone in mifepristone is characterized in that methanol is used as a solvent, an electron capture detector and a dimethyl polysiloxane chromatographic column are adopted, and a gradient heating detection method with the initial temperature of the chromatographic column of 40 ℃ and the final temperature of 250 ℃ is set.
2. An assay method according to claim 1 wherein the dimethylpolysiloxane column used has a specification of 30m x 0.32mm x 0.25 μm of 100% dimethylpolysiloxane.
3. The assay of claim 1 or 2, wherein the gradient temperature rise assay is performed at 40 ℃ for 4-8 minutes, and at 21 ℃ per minute for 4-8 minutes to 250 ℃.
4. The analytical method according to claim 1 or 2, characterized in that it comprises the specific steps of:
1) taking a proper amount of hexafluoroacetone, precisely weighing, taking methanol as a solvent, dissolving and diluting the hexafluoroacetone step by step to prepare a solution of 10 mu g/ml, and obtaining a hexafluoroacetone solution;
2) taking a proper amount of mifepristone, precisely weighing, taking methanol as a solvent, dissolving and diluting to prepare a solution containing 10mg/ml of mifepristone to obtain a mifepristone test sample solution;
3) agilent7890B gas chromatograph, chromatographic column is 100% dimethyl polysiloxane with specification of 30m × 0.32mm × 0.25 μm; the initial temperature of the column temperature is 40 ℃, the column temperature is kept for 4 to 8 minutes, and then the column temperature is increased to 250 ℃ at the rate of 21 ℃ per minute, and the column temperature is kept for 4 to 8 minutes; the sample injection mode is direct sample injection, and the sample injection volume is 1 mu l; the detector is an electron capture detector, and the temperature of the detector is 300 ℃; the temperature of the gasification chamber is 250 ℃; the carrier gas is nitrogen gas, and the concentration is 60 ml/min;
4) and respectively adding a hexafluoroacetone solution and a mifepristone test sample solution, and calculating the content of hexafluoroacetone in mifepristone by adopting an external standard method.
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011112222.4A CN112285227A (en) | 2020-10-16 | 2020-10-16 | Gas chromatography analysis method for hexafluoroacetone in mifepristone |
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| CN202011112222.4A CN112285227A (en) | 2020-10-16 | 2020-10-16 | Gas chromatography analysis method for hexafluoroacetone in mifepristone |
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| CN202011112222.4A Pending CN112285227A (en) | 2020-10-16 | 2020-10-16 | Gas chromatography analysis method for hexafluoroacetone in mifepristone |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0462469A (en) * | 1990-06-29 | 1992-02-27 | Central Glass Co Ltd | Analysis of hexafluoroacetone in 2, 2-bisaryl hexafluoropropane |
| US20080220441A1 (en) * | 2001-05-16 | 2008-09-11 | Birnbaum Eva R | Advanced drug development and manufacturing |
| CN103776917A (en) * | 2013-11-13 | 2014-05-07 | 江苏正大清江制药有限公司 | Method for testing TFA in mifepristone |
| CN111579669A (en) * | 2020-05-26 | 2020-08-25 | 山东东岳未来氢能材料有限公司 | Method for analyzing and measuring hexafluoroacetone content |
-
2020
- 2020-10-16 CN CN202011112222.4A patent/CN112285227A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH0462469A (en) * | 1990-06-29 | 1992-02-27 | Central Glass Co Ltd | Analysis of hexafluoroacetone in 2, 2-bisaryl hexafluoropropane |
| US20080220441A1 (en) * | 2001-05-16 | 2008-09-11 | Birnbaum Eva R | Advanced drug development and manufacturing |
| CN103776917A (en) * | 2013-11-13 | 2014-05-07 | 江苏正大清江制药有限公司 | Method for testing TFA in mifepristone |
| CN111579669A (en) * | 2020-05-26 | 2020-08-25 | 山东东岳未来氢能材料有限公司 | Method for analyzing and measuring hexafluoroacetone content |
Non-Patent Citations (3)
| Title |
|---|
| C.GEFFROY-RODIER 等: "Gas chromatography–mass spectrometry of hexafluoroacetone derivatives: First time utilization of a gaseous phase derivatizing agent for analysis of extraterrestrial amino acids", 《JOURNAL OF CHROMATOGRAPHY A》 * |
| 曾昌华 等: "六氟环氧丙烷及六氟丙酮的色谱分析方法研究", 《有机氟工业》 * |
| 陈新康: "六氟环氧丙烷的制备", 《有机氟工业》 * |
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Application publication date: 20210129 |