CN109085277A - The detection method of residual solvent pyridine in a kind of cefminox sodium - Google Patents
The detection method of residual solvent pyridine in a kind of cefminox sodium Download PDFInfo
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- CN109085277A CN109085277A CN201810804135.1A CN201810804135A CN109085277A CN 109085277 A CN109085277 A CN 109085277A CN 201810804135 A CN201810804135 A CN 201810804135A CN 109085277 A CN109085277 A CN 109085277A
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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
- 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
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Abstract
The present invention relates to a kind of detection methods of residual solvent pyridine in cefminox sodium, pyridine residue detection in Cefminox sodium sample is used and adds alkali external standard method, certain density sodium hydroxide solution is added in test sample, make pyridine separate out in the solution, to reach effective vapor liquid equilibrium in ml headspace bottle, to realize the accuracy of pyridine residue detection, this plus alkali external standard method is a kind of detection method for being more suitable for residual solvent pyridine in cefminox sodium, has the advantages that easy to operate, inspection cost is low etc..
Description
Technical field
The present invention relates to the detection method of medical product, in particular to the inspection of residual solvent pyridine in a kind of cefminox sodium
Survey method.
Background technique
Cefminox sodium is cephamycin-type antibiotic, highly stable to beta-lactamase, to Escherichia coli, the primary bar of Cray
Bacterium, proteus, Bacillus influenzae, bacteroid and streptococcus have stronger antibacterial activity, are important a line drug.In Cefminox
In the production of sodium, the stronger organic solvent pyridine of catalytic action has been used, which is hexa-atomic containing nitrogen heteroatom
Heterocyclic compound, character are colourless or yellowish liquid, foul smelling.Pyridine and its homologue be present in Dippel's oil, coal tar,
Coal gas, shale oil, in petroleum.Pyridine industrially can be used as denaturant, dyeing auxiliaries, and a series of products of synthesis (including medicine
Product, disinfectant, dyestuff etc.) raw material.On October 27th, 2017, international cancer research institution of the World Health Organization announce carcinogenic
The reference of object inventory edit, pyridine is in 2B class carcinogenic substance inventory.
Residual solvent is very important project in the detection of drug, is the important component of drug quality control,
In chemical synthesis, some special solvents such as pyridine used etc. refers to especially drug or API (active pharmaceutical ingredient) in ICH
It leads in principle and is provided in the guideline of Q3C residual solvent, pyridine, which belongs to the solvent that should be limited i.e. second class solvent its limit, to be wanted
It asks as≤200PPm (0.02%).If detected with some conventional methods, because of the defect of method itself, accuracy and quantitative
There is a problem that obvious, testing result inaccuracy is also unreliable, in this way its residual quantity of product just cannot be true
Reflection, this will seriously affect the quality of product.Immeasurable harm is caused using patient body to vast, or even jeopardizes patient
Life.
Summary of the invention
For the defect and problem in the presence of above-mentioned background technique, it is an object of the present invention to provide in a kind of cefminox sodium
The detection method of residual solvent pyridine can accurately and efficiently detect the residual quantity of solvent pyridine in cefminox sodium, determine
Whether it is in defined limit, to ensure that the quality of drug cefminox sodium, reduces or eliminates patient in use process
In hazard factor, reduce allergic reaction, thus achieve the purpose that protection and improve patient health, the invention provides a kind of behaviour
Work is easy, inspection cost is low and is more suitable for detecting the remaining detection method of solvent pyridine in cefminox sodium.
In order to achieve the above object, the invention provides the following technical scheme:
The detection method of residual solvent pyridine, includes the following steps: in a kind of cefminox sodium of the invention
Step 1, the preparation of sodium hydroxide solution, precision weigh sodium hydroxide 0.5-10g, add purified water molten to 1000ml
Measuring bottle shakes up；
Step 2, the preparation of reference substance solution, precision weigh pyridine 20mg and are placed in 100ml volumetric flask, and step 1 is added
In sodium hydroxide solution be diluted to scale, shake up, then precision pipettes 10ml and is placed in 100ml volumetric flask, be added step 1 in
Sodium hydroxide solution be diluted to scale, shake up, as reference substance solution；
Step 3, the preparation of test solution, precision weigh test sample 0.5g, set in 20ml ml headspace bottle, and step 1 is added
In sodium hydroxide solution 5ml dissolution, shake up, as test solution；
Step 4, the preparation of blank solution, the sodium hydroxide solution 5ml in accurate removing step one set 20ml ml headspace bottle
In, sealing, as blank solution；
Gas phase color is arranged using the chromatographic column of -94% dimethyl polysiloxane capillary column of 6% cyanogen propylbenzene in step 5
Injector temperature, column temperature, detector temperature, head space equilibrium temperature, the flow velocity, split ratio of spectrometer；
Step 6, system suitability operation, the reference substance solution 5ml that precision measures in step 2 are set in 20ml ml headspace bottle,
It covers, sealing, 5 bottles of preparation, each needle of continuous sample introduction, and records spectrogram, five for the opposite mark according to solvent peak area in spectrogram
Quasi- deviation is not more than 15%, and theoretical cam curve is not less than 5000；
Step 7, after system suitability is qualified, it is molten that precision measures the test solution in step 3, the blank in step 4
Liquid successively sample introduction, every bottle, respectively into a needle, is detected, and record chromatogram by the chromatographic condition in step 5；
Step 8 calculates, and by external standard method, is control with peak area obtained by the contrast solution in step 6, calculates each solvent
Content.
Further, in step 5, the injector temperature of gas chromatograph is 200-250 DEG C.
Further, in step 5, the column temperature of gas chromatograph is 35-45 DEG C, is maintained 3 minutes, per minute with 35-45 DEG C
200 DEG C are risen to, is maintained 5 minutes.
Further, in step 5, the detector temperature of gas chromatograph is 220-280 DEG C.
Further, in step 5, the head space equilibrium temperature of gas chromatograph is 65-75 DEG C.
Further, in step 5, the flow velocity of gas chromatograph is 1-2ml/ minutes.
Further, in step 5, the split ratio of gas chromatograph is 10-50:1.
Gas chromatograph can obtain accurate pyridine testing result in above-mentioned setting range.
The present invention using alkali external standard method is added, i.e., is added one to pyridine residue detection in Cefminox sodium sample in test sample
The sodium hydroxide solution for determining concentration makes pyridine separate out in the solution, thus reach effective vapor liquid equilibrium in ml headspace bottle,
To realize the accuracy of pyridine residue detection, this plus alkali external standard method is that one kind is more suitable for residual solvent in cefminox sodium
The detection method of pyridine has the advantages that easy to operate, inspection cost is low etc..
Detailed description of the invention
Fig. 1 is the gas chromatogram under the conditions of embodiment 1；
Fig. 2 is the gas chromatogram under the conditions of embodiment 2.
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical solution of the present invention is clearly and completely described, it is clear that
Described embodiments are only a part of the embodiments of the present invention, instead of all the embodiments.Based on the implementation in the present invention
Example, every other embodiment obtained by those of ordinary skill in the art without making creative efforts belong to
The scope of protection of the invention.
Embodiment 1
Step 1, the sodium hydroxide solution that concentration is 0.1% are prepared, and sodium hydroxide 1g is weighed, accurately weighed, are added
In 1000ml measuring bottle, shaken up with purified water dissolved dilution to scale.
Step 2, the preparation of reference substance solution, precision weigh pyridine 20mg and are placed in 100ml volumetric flask, add 0.1% hydrogen
Sodium hydroxide solution is diluted to scale, shakes up, then precision pipettes 10ml and is placed in 100ml volumetric flask, adds 0.1% sodium hydroxide molten
Liquid is diluted to scale, shakes up to get as reference substance solution, concentration 0.02mg/ml.
Step 3, the preparation of test solution, precision weigh test sample 0.5g, set in 20ml ml headspace bottle, add 0.1% hydrogen
Sodium hydroxide solution 5ml dissolution, shakes up, as test solution.
Step 4, the preparation of blank solution, the sodium hydroxide solution 5ml that precision pipettes 0.1% is set in 20ml ml headspace bottle, close
Envelope, as blank solution.
Step 5, the column model used is DB-624, -94% dimethyl polysiloxane capillary of 6% cyanogen propylbenzene
Column, specification are 0.32mm × 30m × 1.8 μm, and the injector temperature of gas chromatograph is 200 DEG C, sample volume 1ml, and column temperature is
40 DEG C maintain 3 minutes, rise to 200 DEG C per minute with 40 DEG C, maintain 5 minutes, and detector is flame ionization ditector, detection
Device temperature is 250 DEG C, and head space equilibrium temperature is 70 DEG C, is balanced 30 minutes, and carrier gas is nitrogen, and flow velocity is 1.5ml/ minutes, is shunted
Than for 30:1.
Step 6, system suitability, precision measure reference substance solution 5ml and set in 20ml ml headspace bottle, cover, sealing, preparation 5
Bottle, each needle of continuous sample introduction, and spectrogram is recorded, five are not more than for the relative standard deviation RSD according to solvent peak area in spectrogram
15%, theoretical cam curve is not less than 5000.
Step 7, detect program and tested as follows after system suitability is qualified: precision measures blank solution, test sample
Solution successively sample introduction, every bottle, respectively into a needle, is detected, and record chromatogram by chromatographic condition as above.
Step 8 is control with peak area obtained by contrast solution, is calculated the content of each solvent, calculation formula by external standard method
It is as follows:
In formula: Mr-reference substance weight (mg)；
Cr-reference substance purity；
Ar-reference substance peak area；
AS-sample peak area；
Ms-example weight (g)；
Nr-control extension rate；
Ns-sample extension rate.
It is computed the residual content 0.01% of pyridine.
Embodiment 2
Step 1, the sodium hydroxide solution that concentration is 0.5% are prepared, and sodium hydroxide 5g is weighed, accurately weighed, are added
In 1000ml measuring bottle, shaken up with purified water dissolved dilution to scale.
Step 2, the preparation of reference substance solution, precision weigh pyridine 20mg and are placed in 100ml volumetric flask, add 0.5% hydrogen-oxygen
Change sodium solution and be diluted to scale, shakes up, then precision pipettes 10ml and is placed in 100ml volumetric flask, adds 0.5% sodium hydroxide solution dilute
Release to scale, shake up to get.As reference substance solution.
Step 3, the preparation of test solution, precision weigh test sample 0.5g, set in 20ml ml headspace bottle, add 0.5% hydrogen-oxygen
Change sodium solution 5ml dissolution, shakes up, as test solution.
Step 4, the preparation of blank solution, precision pipettes 0.5% sodium hydroxide solution 5ml and sets in 20ml ml headspace bottle, close
Envelope, as blank solution.
Step 5, the column model used is DB-624, -94% dimethyl polysiloxane capillary of 6% cyanogen propylbenzene
Column, specification are 0.32mm × 30m × 1.8 μm, and the injector temperature of gas chromatograph is 200 DEG C, sample volume 1ml, and column temperature is
It 40 DEG C, maintains 3 minutes, rises to 200 DEG C per minute with 40 DEG C, maintain 5 minutes, detector is flame ionization ditector, inspection
Surveying device temperature is 250 DEG C, and head space equilibrium temperature is 70 DEG C, is balanced 30 minutes, and carrier gas is nitrogen, and flow velocity is 1.5ml/ minutes, point
Stream is than being 30:1.
Step 6, system suitability, precision measure reference substance solution 5ml and set in 20ml ml headspace bottle, cover, sealing, preparation 5
Bottle, each needle of continuous sample introduction, and spectrogram is recorded, five are not more than for the relative standard deviation RSD according to solvent peak area in spectrogram
15%, theoretical cam curve is not less than 5000.
Step 7 is tested as follows after system suitability is qualified, and precision measures blank solution, test solution successively
Sample introduction, every bottle, respectively into a needle, is detected, and record chromatogram by chromatographic condition as above.
Step 8 is control with peak area obtained by contrast solution, is calculated the content of each solvent, calculation formula by external standard method
It is as follows:
In formula: Mr-reference substance weight (mg)；
Cr-reference substance purity；
Ar-reference substance peak area；
AS-sample peak area；
Ms-example weight (g)；
Nr-control extension rate；
Ns-sample extension rate.
It is computed the residual content 0.01% of pyridine.
The above description is merely a specific embodiment, but scope of protection of the present invention is not limited thereto, any
Those familiar with the art in the technical scope disclosed by the present invention, can easily think of the change or the replacement, and should all contain
Lid is within protection scope of the present invention.Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.
Claims (7)
1. the detection method of residual solvent pyridine in a kind of cefminox sodium, which comprises the steps of:
Step 1, the preparation of sodium hydroxide solution, precision weigh sodium hydroxide 0.5-10g, add purified water to the molten measuring bottle of 1000ml,
It shakes up；
Step 2, the preparation of reference substance solution, precision weigh pyridine 20mg and are placed in 100ml volumetric flask, are added in step 1
Sodium hydroxide solution is diluted to scale, shakes up, then precision pipettes 10ml and is placed in 100ml volumetric flask, and the hydrogen in step 1 is added
Sodium hydroxide solution is diluted to scale, shakes up, as reference substance solution；
Step 3, the preparation of test solution, precision weigh test sample 0.5g, set in 20ml ml headspace bottle, are added in step 1
Sodium hydroxide solution 5ml dissolution, shakes up, as test solution；
Step 4, the preparation of blank solution, the sodium hydroxide solution 5ml in accurate removing step one is set in 20ml ml headspace bottle, close
Envelope, as blank solution；
Gas chromatograph is arranged using the chromatographic column of -94% dimethyl polysiloxane capillary column of 6% cyanogen propylbenzene in step 5
Injector temperature, column temperature, detector temperature, head space equilibrium temperature, flow velocity, split ratio；
Step 6, system suitability operation, the reference substance solution 5ml that precision measures in step 2 set in 20ml ml headspace bottle, cover,
Sealing, 5 bottles of preparation, each needle of continuous sample introduction, and spectrogram is recorded, five for the relative standard deviation according to solvent peak area in spectrogram
No more than 15%, theoretical cam curve is not less than 5000；
Step 7, after system suitability is qualified, precision measure the test solution in step 3, the blank solution in step 4 according to
Secondary sample introduction, every bottle, respectively into a needle, is detected, and record chromatogram by the chromatographic condition in step 5；
Step 8 calculates, and by external standard method, is control with peak area obtained by the contrast solution in step 6, calculates containing for each solvent
Amount.
2. the detection method of residual solvent pyridine in a kind of cefminox sodium according to claim 1, which is characterized in that step
In rapid five, the injector temperature of gas chromatograph is 200-250 DEG C.
3. the detection method of residual solvent pyridine in a kind of cefminox sodium according to claim 1, which is characterized in that step
In rapid five, the column temperature of gas chromatograph is 35-45 DEG C, is maintained 3 minutes, rises to 200 DEG C per minute with 35-45 DEG C, maintains 5 points
Clock.
4. the detection method of residual solvent pyridine in a kind of cefminox sodium according to claim 1, which is characterized in that step
In rapid five, the detector temperature of gas chromatograph is 220-280 DEG C.
5. the detection method of residual solvent pyridine in a kind of cefminox sodium according to claim 1, which is characterized in that step
In rapid five, the head space equilibrium temperature of gas chromatograph is 65-75 DEG C.
6. the detection method of residual solvent pyridine in a kind of cefminox sodium according to claim 1, which is characterized in that step
In rapid five, the flow velocity of gas chromatograph is 1-2ml/ minutes.
7. the detection method of residual solvent pyridine in a kind of cefminox sodium according to claim 1, which is characterized in that step
In rapid five, the split ratio of gas chromatograph is 10-50:1.
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112305102A (en) * | 2020-10-19 | 2021-02-02 | 南京格洛特环境工程股份有限公司 | Detection and analysis method for residual solvent pyridine in solid salt |
| CN114414715A (en) * | 2022-01-26 | 2022-04-29 | 武汉九州钰民医药科技有限公司 | Detection method and application of benzene in ceftazidime residual solvent |
| CN115060830A (en) * | 2022-07-05 | 2022-09-16 | 云南大理天新包装材料有限公司 | Method for detecting VOCs solvent residues of paper |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009089076A2 (en) * | 2008-01-10 | 2009-07-16 | Teva Pharmaceutical Industries Ltd. | Processes for the preparation and purification of paliperidone palmitate |
| CN104072520A (en) * | 2014-06-06 | 2014-10-01 | 广东立国制药有限公司 | Synthesis method of cefminox sodium |
| CN105067724A (en) * | 2015-08-05 | 2015-11-18 | 山东省药学科学院 | Method for detecting organic solvent residue in Cetilistat |
| CN105319283A (en) * | 2014-07-17 | 2016-02-10 | 上海市农药研究所 | Method for measuring content of terpyridine |
-
2018
- 2018-07-20 CN CN201810804135.1A patent/CN109085277A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2009089076A2 (en) * | 2008-01-10 | 2009-07-16 | Teva Pharmaceutical Industries Ltd. | Processes for the preparation and purification of paliperidone palmitate |
| CN104072520A (en) * | 2014-06-06 | 2014-10-01 | 广东立国制药有限公司 | Synthesis method of cefminox sodium |
| CN105319283A (en) * | 2014-07-17 | 2016-02-10 | 上海市农药研究所 | Method for measuring content of terpyridine |
| CN105067724A (en) * | 2015-08-05 | 2015-11-18 | 山东省药学科学院 | Method for detecting organic solvent residue in Cetilistat |
Non-Patent Citations (6)
| Title |
|---|
| LUO YI 等: "Comparison of headspace-GC with purge and trap-GC/MS methods in determination of acetaldehyde, acrolein, acrylonitrile and pyridine", 《HEBEI JOURNAL OF INDUSTRIAL SCIENCE & TECHNOLOGY》 * |
| 张辉 等: "顶空气相色谱法测定阿哌沙班原料药中有机残留溶剂的残留量", 《天津药学》 * |
| 王英瑛 等: "顶空气相色谱法测定克林霉素磷酸酯中有机溶剂残留量", 《药物鉴定》 * |
| 王钊 等: "顶空气相色谱-质谱联用测定饮用水中吡啶", 《分析试验室》 * |
| 苟琰 等: "顶空气相法测定亚甲基二膦酸中乙醚和吡啶残留量", 《华西药学杂志》 * |
| 赵翠丽: "气相色谱法在药物残留溶剂测定中的应用研究", 《中国优秀硕士学位论文全文数据库 医药卫生科技辑》 * |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112305102A (en) * | 2020-10-19 | 2021-02-02 | 南京格洛特环境工程股份有限公司 | Detection and analysis method for residual solvent pyridine in solid salt |
| CN114414715A (en) * | 2022-01-26 | 2022-04-29 | 武汉九州钰民医药科技有限公司 | Detection method and application of benzene in ceftazidime residual solvent |
| CN114414715B (en) * | 2022-01-26 | 2024-04-26 | 武汉九州钰民医药科技有限公司 | Method for detecting benzene in ceftazidime residual solvent and application |
| CN115060830A (en) * | 2022-07-05 | 2022-09-16 | 云南大理天新包装材料有限公司 | Method for detecting VOCs solvent residues of paper |
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Application publication date: 20181225 |