CN112034075A - Method for checking limit of residual methyl formate and methanol in metronidazole - Google Patents
Method for checking limit of residual methyl formate and methanol in metronidazole Download PDFInfo
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- CN112034075A CN112034075A CN202011092829.0A CN202011092829A CN112034075A CN 112034075 A CN112034075 A CN 112034075A CN 202011092829 A CN202011092829 A CN 202011092829A CN 112034075 A CN112034075 A CN 112034075A
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- G—PHYSICS
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- 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
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
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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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N2030/067—Preparation by reaction, e.g. derivatising the sample
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Abstract
The invention belongs to the technical field of chemical drug analysis, and particularly relates to a method for checking the limit of residual formic acid in metronidazole. The detection method can avoid the phenomena of high possibility of generating serious tailing, poor hair generation and low thermal stability due to strong polarity of formic acid.
Description
Technical Field
The invention relates to the technical field of chemical drug analysis, in particular to a method for checking the limit of residual formic acid in metronidazole.
Background
Metronidazole, also named metronidazole, metronidazole and the like, has a chemical name of 2-methyl-5-nitroimidazole-1-ethanol, is a nitroimidazole synthetic antibacterial drug, is very wide in clinical application, has the functions of broad-spectrum anti-anaerobe and antiprotozoal, is mainly used for preventing and treating infections caused by anaerobe in clinic, such as respiratory tract, digestive tract, abdominal cavity and pelvic cavity infections, infections of parts such as skin soft tissues, bones and bone joints and the like, and endocarditis, brain abscess, septicemia, meningitis and the like caused by bacteroides fragilis, is also widely used for preventing and treating oral anaerobe infections, and the nitro group of metronidazole is reduced into amino in an anaerobic environment to have the anti-anaerobe function and is ineffective to aerobic bacteria or facultative aerobes; the metronidazole can often remain formic acid in the production process, so that the production quality of metronidazole medicaments can be influenced, and a good detection method is not provided in the prior art, so that the invention provides a method for detecting the limit of the remaining formic acid in metronidazole to solve the defects in the prior art.
Disclosure of Invention
Aiming at the defects of the prior art, the invention provides a method for checking the limit of residual formic acid in metronidazole.
The method comprises the following steps: preparing metronidazole sample solution
Precisely weighing 0.03g of a sample to be tested, putting the sample into a 10ml headspace bottle, precisely weighing 1.0ml of 90% methanol-water, adding the sample into the headspace bottle, finally adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step two: stock solution for checking limit of preparation
Precisely weighing 34mg of sodium formate dihydrate, placing the sodium formate dihydrate into a 100ml measuring flask, adding 90% methanol solution, and fixing the volume;
step three: solution a for checking the limit of distribution
Precisely measuring 1.0ml of the limit check storage solution in the step two, adding 90% methanol-water to fix the volume to 10ml, precisely measuring 1.0ml from the limit check storage solution, placing the solution in a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step four: solution b for checking the limit of distribution
Precisely measuring 1.0ml of the limit inspection solution a in the third step, adding 90% methanol-water to constant volume to 10ml, precisely measuring 1.0ml from the limit inspection solution a, placing the solution in a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step five: preparing a blank solvent
Precisely measuring 1.0ml of 90% methanol-water, putting the solution into a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and quickly sealing;
step six: headspace treatment
Respectively placing the headspace bottles in the first step, the third step, the fourth step and the fifth step into an automatic headspace sample injector, and keeping the temperature for 20min at the bottle temperature of 50 ℃; the quantitative ring temperature is 60 ℃; treating the transmission line at a headspace condition of 70 ℃;
step seven: gas chromatograph analysis processing
Respectively extracting 1ml of gas in each headspace bottle in the sixth step, injecting the gas into a gas chromatograph provided with an InertCap FFAP chromatographic column with the specification of 30m multiplied by 0.32mm multiplied by 0.25 mu m and an FID detector through an automatic headspace injector, and finally enabling the gas chromatograph to pass through a set injection port at the temperature of 200 ℃; keeping the column temperature at 40 ℃ for 8min, then increasing the temperature to 220 ℃ at a heating rate of 60 ℃/min, and keeping the temperature for 2 min; the temperature of the detector is 200 ℃; the flow rate of the nitrogen carrier gas is 1.0 ml/min; with the split 50: 1, deriving data after analyzing and processing the chromatographic conditions, calculating to obtain the content of the formic acid in the limit inspection solution a and the limit inspection solution b, and finally comparing the peak areas of the methyl formate in the metronidazole sample solution with the peak areas of the methyl formate in the limit inspection solution a and the limit inspection solution b, so that the content of the formic acid in the test sample can be judged to be in a corresponding content interval.
The invention has the beneficial effects that: the method avoids the phenomena of easy generation of serious tailing, poor hair generation and low thermal stability caused by strong polarity of formic acid, and converts the formic acid into methyl formate by a derivation method, so that the volatility is better, the thermal stability is higher and the peak type is better in the detection process.
Detailed Description
In order to further understand the present invention, the following detailed description will be made with reference to the following examples, which are only used for explaining the present invention and are not to be construed as limiting the scope of the present invention.
The embodiment provides a method for checking the limit of residual methyl formate and methanol in metronidazole, which comprises the following steps:
the method comprises the following steps: preparing metronidazole sample solution
Precisely weighing 0.03g of a sample to be tested, putting the sample into a 10ml headspace bottle, precisely weighing 1.0ml of 90% methanol-water, adding the sample into the headspace bottle, finally adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step two: stock solution for checking limit of preparation
Precisely weighing 34mg of sodium formate dihydrate, placing the sodium formate dihydrate into a 100ml measuring flask, adding 90% methanol solution, and fixing the volume;
step three: solution a for checking the limit of distribution
Precisely measuring 1.0ml of the limit check storage solution in the step two, adding 90% methanol-water to fix the volume to 10ml, precisely measuring 1.0ml from the limit check storage solution, placing the solution in a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step four: solution b for checking the limit of distribution
Precisely measuring 1.0ml of the limit inspection solution a in the third step, adding 90% methanol-water to constant volume to 10ml, precisely measuring 1.0ml from the limit inspection solution a, placing the solution in a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step five: preparing a blank solvent
Precisely measuring 1.0ml of 90% methanol-water, putting the solution into a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and quickly sealing;
step six: headspace treatment
Respectively placing the headspace bottles in the first step, the third step, the fourth step and the fifth step into an automatic headspace sample injector, and keeping the temperature for 20min at the bottle temperature of 50 ℃; the quantitative ring temperature is 60 ℃; treating the transmission line at a headspace condition of 70 ℃;
step seven: gas chromatograph analysis processing
Respectively extracting 1ml of gas in each headspace bottle in the sixth step, injecting the gas into a gas chromatograph provided with an InertCap FFAP chromatographic column with the specification of 30m multiplied by 0.32mm multiplied by 0.25 mu m and an FID detector through an automatic headspace injector, and finally enabling the gas chromatograph to pass through a set injection port at the temperature of 200 ℃; keeping the column temperature at 40 ℃ for 8min, then increasing the temperature to 220 ℃ at a heating rate of 60 ℃/min, and keeping the temperature for 2 min; the temperature of the detector is 200 ℃; the flow rate of the nitrogen carrier gas is 1.0 ml/min; with the split 50: 1, deriving data after analyzing and processing the chromatographic conditions to obtain the peak area of the methyl formate, calculating the contents of the formic acid in the limit inspection solution a and the limit inspection solution b through the molecular weight of the formic acid and the methyl formate, and finally comparing the peak areas of the methyl formate in the metronidazole sample solution, the limit inspection solution a and the limit inspection solution b to judge that the content of the formic acid in the test sample is in a corresponding content interval.
The method comprises the steps of precisely measuring a certain amount of dihydrate and sodium formate, dissolving the dihydrate and the sodium formate with 90% methanol to prepare a limit checking storage solution, diluting the limit checking storage solution in a certain amount to different concentrations according to different proportions, placing 1.0ml and 100 mu l of concentrated sulfuric acid in a headspace bottle to prepare a limit checking solution a and a limit checking solution b, heating the limit checking storage solution and the 100 mu l of concentrated sulfuric acid by an automatic headspace sample injector to perform acidolysis to form formic acid, and heating and esterifying the formic acid and the metronidazole sample solution in the automatic headspace sample injector to form methyl formate. And finally, comparing the peak areas of the methyl formate in the metronidazole sample solution, the limit checking solution a and the limit checking solution b, and judging that the content of the formic acid in the test sample is in a corresponding content interval.
The foregoing illustrates and describes the principles, general features, and advantages of the present invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are described in the specification and illustrated only to illustrate the principle of the present invention, but that various changes and modifications may be made therein without departing from the spirit and scope of the present invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (8)
1. The method for detecting the residual formic acid in metronidazole is characterized by comprising the following steps: the method comprises the following steps:
the method comprises the following steps: preparing metronidazole sample solution
Precisely weighing 0.03g of a sample to be tested, putting the sample into a 10ml headspace bottle, precisely weighing 1.0ml of 90% methanol-water, adding the sample into the headspace bottle, finally adding 100 mu l of concentrated sulfuric acid, and rapidly sealing;
step two: stock solution for checking limit of preparation
Precisely weighing 34mg of sodium formate dihydrate, placing the sodium formate dihydrate into a 100ml measuring flask, adding 90% methanol solution, and fixing the volume;
step three: solution a for checking the limit of distribution
Precisely measuring 1.0ml of the limit checking storage solution in the step two, adding 90% methanol-water to fix the volume to 10ml, precisely measuring 1.0ml from the limit checking storage solution, putting the solution into a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and rapidly sealing to obtain a limit checking solution a, wherein the content of formic acid in the limit checking solution a is 15.04 mu g/ml;
step four: solution b for checking the limit of distribution
Precisely measuring 1.0ml of the limit checking solution a in the third step, adding 90% methanol-water to fix the volume to 10ml, precisely measuring 1.0ml from the limit checking solution a, placing the solution in a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and rapidly sealing to obtain a limit checking solution b, wherein the content of formic acid in the limit checking solution b is 1.504 mu g/ml;
step five: preparing a blank solvent
Precisely measuring 1.0ml of 90% methanol-water, putting the solution into a 10ml headspace bottle, adding 100 mu l of concentrated sulfuric acid, and quickly sealing to obtain a blank solvent;
step six: headspace treatment
Respectively placing headspace bottles filled with a blank solvent, a limit checking solution b, a limit checking solution a and a metronidazole sample solution into an automatic headspace sample injector, and treating according to headspace conditions;
step seven: gas chromatograph analysis processing
And (3) respectively extracting 1ml of gas in each headspace bottle in the step six, injecting the gas into a gas chromatograph through an automatic headspace injector, finally analyzing and processing the gas by the gas chromatograph according to set chromatographic conditions, deriving data, calculating to obtain the content of the formic acid in the limit checking solution a and the limit checking solution b, and finally comparing the peak areas of the methyl formate in the metronidazole sample solution, the limit checking solution a and the limit checking solution b, so that the content of the formic acid in the sample can be judged to be in a corresponding content interval.
2. The method for detecting the limit of residual formic acid in metronidazole as claimed in claim 1, characterized in that: the headspace conditions in the sixth step are as follows: the bottle temperature of each headspace bottle is 50 ℃, the holding time is 20min, the temperature of the quantitative ring is 60 ℃, and the temperature of the transmission line is 70 ℃.
3. The method for detecting the limit of residual formic acid in metronidazole as claimed in claim 1, characterized in that: and the gas chromatograph in the step seven is provided with an FID type detector.
4. The method for detecting the limit of residual formic acid in metronidazole as claimed in claim 1, characterized in that: the capillary column in step seven is an InertCap FFAP column of 30m × 0.32mm × 0.25 μm or other column of similar potency.
5. The method for detecting the limit of residual formic acid in metronidazole as claimed in claim 1, characterized in that: the column temperature of the capillary column in the seventh step is maintained for 8min at 40 ℃, and then is increased to 220 ℃ at the heating rate of 60 ℃/min and maintained for 2 min.
6. The method for detecting the limit of residual formic acid in metronidazole as claimed in claim 1, characterized in that: and the temperature of a sample inlet of the gas chromatograph in the seventh step is 200 ℃.
7. The method for detecting the limit of residual formic acid in metronidazole as claimed in claim 1, characterized in that: and the carrier gas of the gas chromatograph in the seventh step is nitrogen, the flow rate is 1.0ml/min, and the split ratio is 50: 1.
8. the method for detecting the limit of residual formic acid in metronidazole as claimed in claim 3, characterized in that: the detection temperature of the FID detector is 200 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN202011092829.0A CN112034075A (en) | 2020-10-13 | 2020-10-13 | Method for checking limit of residual methyl formate and methanol in metronidazole |
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| CN202011092829.0A CN112034075A (en) | 2020-10-13 | 2020-10-13 | Method for checking limit of residual methyl formate and methanol in metronidazole |
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102901784A (en) * | 2012-11-02 | 2013-01-30 | 江苏吉贝尔药业有限公司 | Method for performing headspace gas chromatographic detection on formic acid in aceclofenac bulk pharmaceutical chemicals |
| CN103630628A (en) * | 2013-12-05 | 2014-03-12 | 常州亚邦齐晖医药化工有限公司 | Method used for detecting formic acid residue in imidazole vermifuges |
| CN104502491A (en) * | 2015-01-20 | 2015-04-08 | 陕西汉江药业集团股份有限公司 | Method for determining bulk drug oxfendazole solvent residues by headspace sampling |
| CN108828124A (en) * | 2018-06-27 | 2018-11-16 | 湖北省宏源药业科技股份有限公司 | Methyl formate and methanol limit test method are remained in metronidazole |
| US20210285920A1 (en) * | 2018-07-07 | 2021-09-16 | Zhejiang Huahai Pharmaceutical Co., Ltd | Detection method for n-nitrosodimethylamine impurities |
-
2020
- 2020-10-13 CN CN202011092829.0A patent/CN112034075A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102901784A (en) * | 2012-11-02 | 2013-01-30 | 江苏吉贝尔药业有限公司 | Method for performing headspace gas chromatographic detection on formic acid in aceclofenac bulk pharmaceutical chemicals |
| CN103630628A (en) * | 2013-12-05 | 2014-03-12 | 常州亚邦齐晖医药化工有限公司 | Method used for detecting formic acid residue in imidazole vermifuges |
| CN104502491A (en) * | 2015-01-20 | 2015-04-08 | 陕西汉江药业集团股份有限公司 | Method for determining bulk drug oxfendazole solvent residues by headspace sampling |
| CN108828124A (en) * | 2018-06-27 | 2018-11-16 | 湖北省宏源药业科技股份有限公司 | Methyl formate and methanol limit test method are remained in metronidazole |
| US20210285920A1 (en) * | 2018-07-07 | 2021-09-16 | Zhejiang Huahai Pharmaceutical Co., Ltd | Detection method for n-nitrosodimethylamine impurities |
Non-Patent Citations (1)
| Title |
|---|
| 孟军等: "顶空气相色谱法测定阿扎胞苷中有机溶剂残留量", 《中国药师》 * |
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Application publication date: 20201204 |