CN104155370A - Analytical method for determination of ethanol residual quantity in coating layer of tablet - Google Patents
Analytical method for determination of ethanol residual quantity in coating layer of tablet Download PDFInfo
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- CN104155370A CN104155370A CN201310175426.6A CN201310175426A CN104155370A CN 104155370 A CN104155370 A CN 104155370A CN 201310175426 A CN201310175426 A CN 201310175426A CN 104155370 A CN104155370 A CN 104155370A
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Abstract
The invention belongs to the technical field of medicines, and in particular relates to an analytical method for determination of ethanol residual quantity in a coating layer of a tablet. According to the method, ethanol residual quantity in coated tablet powder is determined by use of headspace capillary gas chromatography, the effects of residual ethanol in uncoated tablets can be excluded, the ethanol residual value taken into the tablet by the ethanol coating layer can be accurately determined by the method, and an important reference for the improvement of the ethanol coating process is provided.
Description
Technical field
The present invention relates to medical technical field, particularly a kind of analytical approach of measuring Residual ethanol.
Background technology
" Chinese Pharmacopoeia " version in 2010 has increased the dissolvent residual project of many medicines with respect to front version pharmacopeia, controlling dissolvent residual also becomes the trend that medical industry is produced from now on." Chinese Pharmacopoeia " specified that in medicine, alcohol residue must not cross 0.5% for 2010 in version, in view of current ethanol is a kind of common dressing solvent, in production, can go out the method for Residual ethanol in tablet coatings by Accurate Measurement in the urgent need to a kind of, to instruct the improvement of dressing operation.
Summary of the invention
The technical problem to be solved in the present invention is: a kind of method that uses the ethanol content that the preparation medicine of ethanol dressing brings in dressing process that effectively detects is provided.
The invention provides a kind of analytical approach of measuring Residual ethanol in tablet coatings, step is as follows:
(1) tablet of getting after dressing is made powder, and precision takes in a certain amount of DMF of being dissolved in;
(2) adopt Residual ethanol in the tablet powder after head space capillary gas chromatography dressing;
(3) get not dressing plain sheet before and make powder, precision takes in a certain amount of DMF of being dissolved in, and adopts wherein Residual ethanol of head space capillary gas chromatography;
(4) Residual ethanol in the tablet after dressing is deducted to Residual ethanol in the plain sheet before dressing not and obtain Residual ethanol in coatings.
Due in the preparation process of bulk drug; or in pelletization, usually can use ethanol; therefore in dressing plain sheet before, may not have alcohol residue; conventional method is directly measured the ethanol content in the tablet after dressing; the result obtaining probably cannot reflect the ethanol content in coatings accurately; above-mentioned steps (4) has effectively been got rid of the interference of ethanol content in the plain sheet before dressing not; no matter in the plain sheet before dressing, whether do not contain alcohol residue, can not affect the mensuration to Residual ethanol in coatings.
Head space capillary gas chromatography chromatographic condition is:
Chromatographic column: DB-624 type capillary chromatographic column; Column temperature: 50 DEG C of initial temperatures, maintain 3 minutes, rise to 90 DEG C with the speed of 10 DEG C/min, maintain 2 minutes, rise to 200 DEG C with the speed of 35 DEG C/min, maintain 2 minutes; 180 DEG C of injector temperatures; Detecting device is flame ionization ditector, 250 DEG C of temperature; Carrier gas: nitrogen; 85 DEG C of head space equilibrium temperatures; Equilibration time 30 minutes.
What preferably, in described mensuration tablet coatings, the analytical approach of Residual ethanol adopted is external standard method.Comprise the following steps: get appropriate amount of ethanol, accurately weighed, add DMF and dissolve and quantitatively dilute and make the solution that every 1ml contains 0.2mg, precision measures 5.0ml, puts in 20ml head space bottle sealing, product solution in contrast; Get the about 0.2g of powder after preparation medicine porphyrize, accurately weighed, put in 20ml head space bottle, add DMF5.0ml, sealing, as need testing solution; Separately get not dressing plain sheet before and make the about 0.2g of powder, accurately weighed, put in 20ml head space bottle, add DMF5.0ml, sealing, as blank solution.Get above-mentioned solution, headspace sampling, records chromatogram, by external standard method with calculated by peak area Residual ethanol.
Embodiment
Embodiment 1
Diltiazem (upper Hisense friendship everything medicine company, 90mg) alcohol residue quantitative determination and method validation
Get the about 0.2g(of powder after 20 porphyrizes of this product divide get nine parts) put in 20ml head space bottle, add respectively 5.0ml contrast storing solution 22.0ml, 5.0ml contrast storing solution 1(tri-levels, each three parts), thinning agent DMF0ml, 3.0ml, 0ml, seal 85 DEG C of heating 30 minutes.
Head space capillary gas chromatography chromatographic condition is:
Chromatographic column: DB-624 type capillary chromatographic column; Column temperature: 50 DEG C of initial temperatures, maintain 3 minutes, rise to 90 DEG C with the speed of 10 DEG C/min, maintain 2 minutes, rise to 200 DEG C with the speed of 35 DEG C/min, maintain 2 minutes; 180 DEG C of injector temperatures; Detecting device is flame ionization ditector, 250 DEG C of temperature; Carrier gas: nitrogen; 85 DEG C of head space equilibrium temperatures; Equilibration time 30 minutes.
Each level all adopts 3 batches of finished products to do respectively average recovery, 1,4,7; 2,5,8; 3,6,9.
Average recovery evaluation criterion: average recovery 90.0%～110.0%; RSD≤10.0%
Get the powder after diltiazem (upper Hisense friendship everything medicine company) 20 porphyrizes of plain sheet before dressing not, measure Residual ethanol, measurement result: do not detect alcohol residue according to preceding method.
Embodiment 2
Simvastatin sheet (upper Hisense friendship everything medicine company, 20mg) alcohol residue quantitative determination and method validation
Get the about 0.2g(of powder after 20 porphyrizes of this product divide get nine parts) put in 20ml head space bottle, add respectively 5.0ml contrast storing solution 22.0ml, 5.0ml contrast storing solution 1(tri-levels, each three parts), thinning agent DMF0ml, 3.0ml, 0ml, seal 85 DEG C of heating 30 minutes.
Head space capillary gas chromatography chromatographic condition is:
Chromatographic column: DB-624 type capillary chromatographic column; Column temperature: 50 DEG C of initial temperatures, maintain 3 minutes, rise to 90 DEG C with the speed of 10 DEG C/min, maintain 2 minutes, rise to 200 DEG C with the speed of 35 DEG C/min, maintain 2 minutes; 180 DEG C of injector temperatures; Detecting device is flame ionization ditector, 250 DEG C of temperature; Carrier gas: nitrogen; 85 DEG C of head space equilibrium temperatures; Equilibration time 30 minutes.
Each level all adopts 3 batches of finished products to do respectively average recovery, 1,4,7; 2,5,8; 3,6,9.
Average recovery evaluation criterion: average recovery 90.0%～110.0%; RSD≤10.0%
Get the powder after Simvastatin sheet (upper Hisense friendship everything medicine company, 20mg) 20 porphyrizes of plain sheet before dressing not, measure Residual ethanol, measurement result: do not detect alcohol residue according to preceding method.
Embodiment 3 quantitative limit, detectability and linear evaluation
Quantitative limit: evaluate and be about 10:1 according to signal to noise ratio (S/N ratio), RSD<10.0%
Operation steps:
Storing solution: get ethanol reference substance 30mg and put in 100ml measuring bottle and be diluted to scale with DMF.
Contrast liquid: get 3ml storing solution and put 25ml measuring bottle DMF and be diluted to scale, get 1ml and put in 100ml measuring bottle and be diluted to scale with DMF, get 5ml and put and seal 85 DEG C of balances 30 minutes in 20ml head space bottle.
Detectability: evaluate and be about 3:1 according to signal to noise ratio (S/N ratio), RSD<15.0%
Operation steps:
Storing solution: get ethanol reference substance 30mg and put in 100ml measuring bottle and be diluted to scale with DMF.
Contrast liquid: get 3ml storing solution and put 25ml measuring bottle DMF and be diluted to scale, get 3ml and put in 10ml measuring bottle and be diluted to scale with DMF, get 1ml and put in 100ml measuring bottle and be diluted to scale with DMF, get 5ml and put and seal 85 DEG C of balances 30 minutes in 20ml head space bottle.
Linear: evaluation criterion R>0.999
Operation steps:
Storing solution: get ethanol reference substance 30mg and put in 100ml measuring bottle and be diluted to scale with DMF.
(1) get storing solution 3ml and put 25ml measuring bottle DMF and be diluted to scale, get 1ml and put in 100ml measuring bottle and be diluted to scale with DMF;
(2) getting storing solution 2.5ml puts in 10ml measuring bottle and is diluted to scale with DMF;
(3) getting storing solution 4.0ml puts in 10ml measuring bottle and is diluted to scale with DMF;
(4) getting storing solution 6.7ml puts in 10ml measuring bottle and is diluted to scale with DMF;
(5) getting storing solution 7.8ml puts in 10ml measuring bottle and is diluted to scale with DMF;
(6) getting storing solution 8.8ml puts in 10ml measuring bottle and is diluted to scale with DMF;
(7) storing solution
Above-mentioned solution is respectively got 5ml and is put and in 20ml head space bottle, seal 85 DEG C of balances 30 minutes, sample introduction respectively.
A=-0.39453+450.36c
Sum up: from above-mentioned summary sheet, can find out, accuracy and the precision of 2 piece of data all conform with the regulations, and the first piece of data average recovery rate is 102.01%, recovery RSD
9be 5.88%, repeated RSD
6be that 4.41%, the second piece of data average recovery rate is 103.66%, recovery RSD
9be 3.83%, repeated RSD
6be 4.52%; Quantitative limit RSD=3.9%, signal to noise ratio (S/N ratio)=10.2; Detectability RSD=11.3%, signal to noise ratio (S/N ratio)=3.3; Linearly dependent coefficient R=0.9997; All meet standard.When the method can apply to measure with ethanol dressing, layer is brought the practice examining of the alcohol residue value of tablet into, and the improved important references that provides of ethanol art for coating is provided.
Claims (3)
1. an analytical approach of measuring Residual ethanol in tablet coatings, step is as follows:
(1) tablet of getting after dressing is made powder, and precision takes in a certain amount of DMF of being dissolved in;
(2) adopt Residual ethanol in the tablet powder after head space capillary gas chromatography dressing;
(3) get not dressing plain sheet before and make powder, precision takes in a certain amount of DMF of being dissolved in, and adopts wherein Residual ethanol of head space capillary gas chromatography;
(4) Residual ethanol in the tablet after dressing is deducted to Residual ethanol in the plain sheet before dressing not and obtain Residual ethanol in coatings.
2. the analytical approach of Residual ethanol in mensuration tablet coatings as claimed in claim 1, is characterized in that described head space capillary gas chromatography chromatographic condition is:
Chromatographic column: DB-624 type capillary chromatographic column; Column temperature: 50 DEG C of initial temperatures, maintain 3 minutes, rise to 90 DEG C with the speed of 10 DEG C/min, maintain 2 minutes, rise to 200 DEG C with the speed of 35 DEG C/min, maintain 2 minutes; 180 DEG C of injector temperatures; Detecting device is flame ionization ditector, 250 DEG C of temperature; Carrier gas: nitrogen; 85 DEG C of head space equilibrium temperatures; Equilibration time 30 minutes.
3. the analytical approach of Residual ethanol in mensuration tablet coatings as claimed in claim 1 or 2, it is characterized in that described method is external standard method, comprise the following steps: get appropriate amount of ethanol, accurately weighed, add DMF and dissolve and quantitatively dilute and make the solution that every 1ml contains 0.2mg, precision measures 5.0ml, puts in 20ml head space bottle, sealing, product solution in contrast; Get the about 0.2g of powder after preparation medicine porphyrize, accurately weighed, put in 20ml head space bottle, add DMF5.0ml, sealing, as need testing solution; Separately get not dressing plain sheet before and make the about 0.2g of powder, accurately weighed, put in 20ml head space bottle, add DMF5.0ml, sealing, as blank solution; Get above-mentioned solution, headspace sampling, records chromatogram, by external standard method with calculated by peak area Residual ethanol.
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| CN201310175426.6A CN104155370A (en) | 2013-05-13 | 2013-05-13 | Analytical method for determination of ethanol residual quantity in coating layer of tablet |
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| CN201310175426.6A CN104155370A (en) | 2013-05-13 | 2013-05-13 | Analytical method for determination of ethanol residual quantity in coating layer of tablet |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110208440A (en) * | 2019-07-24 | 2019-09-06 | 鲁南制药集团股份有限公司 | The detection method of Residual ethanol in amoxicillin and clavulanate potassium preparation |
| CN115561353A (en) * | 2022-09-22 | 2023-01-03 | 河北省药品医疗器械检验研究院(河北省化妆品检验研究中心) | Method for measuring amount of ethanol in ergot maleate tablets |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102949370A (en) * | 2012-11-27 | 2013-03-06 | 贵州信邦制药股份有限公司 | Roflumilast tablets as well as preparation method and detection method thereof |
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2013
- 2013-05-13 CN CN201310175426.6A patent/CN104155370A/en active Pending
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102949370A (en) * | 2012-11-27 | 2013-03-06 | 贵州信邦制药股份有限公司 | Roflumilast tablets as well as preparation method and detection method thereof |
Non-Patent Citations (3)
| Title |
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| 冯明霞， 王雪芹， 刘杰: "顶空气相色谱法测定伊曲康哇薄膜衣片中二氯甲烷及乙醇残留量", 《药物分析杂志》 * |
| 时涛， 陈振德: "顶空气相色谱法测定制剂包衣中乙醇和二氯甲烷残留量", 《西北药学杂志》 * |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110208440A (en) * | 2019-07-24 | 2019-09-06 | 鲁南制药集团股份有限公司 | The detection method of Residual ethanol in amoxicillin and clavulanate potassium preparation |
| CN115561353A (en) * | 2022-09-22 | 2023-01-03 | 河北省药品医疗器械检验研究院(河北省化妆品检验研究中心) | Method for measuring amount of ethanol in ergot maleate tablets |
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Application publication date: 20141119 |