CN101008637B - Quality control method of fasudil hydrochloride injection - Google Patents
Quality control method of fasudil hydrochloride injection Download PDFInfo
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- CN101008637B CN101008637B CN2007100002261A CN200710000226A CN101008637B CN 101008637 B CN101008637 B CN 101008637B CN 2007100002261 A CN2007100002261 A CN 2007100002261A CN 200710000226 A CN200710000226 A CN 200710000226A CN 101008637 B CN101008637 B CN 101008637B
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Abstract
This invention relates to alcaine telfairic injection liquid quality control method, which comprises the following steps: property observing, content identifying; content testing and testing component volume.
Description
Technical field:
The present invention relates to a kind of method of quality control of pharmaceutical preparation, particularly a kind of method of quality control that is used for the medicine Fasudic hydrochloride parenteral solution of the ICVD doing well,improving that cerebral vasospasm after subarachnoid hemorrhage etc. causes.
Background technology:
Fasudic hydrochloride, English name: Fasudil is that a kind of kinases inhibitor is the intracellular calcium antagonist, it is a kind of medicine for the treatment of ischemic cerebral disease, the pharmaceutical preparation listing of existing injection.The Fasudic hydrochloride structure is special, is difficult to effectively control the quality of Fasudic hydrochloride preparation, thereby influences the production of product and ensure the quality of products.
For effectively controlling product quality, we have set up the new method of quality control of fasudil hydrochloride injection, this method adopts nickel hydroxide test paper and ultraviolet spectrophotometry that Fasudic hydrochloride is differentiated, adopts UV-VIS spectrophotometry that Fasudic hydrochloride is carried out assay.This method of quality control precision, sensitivity, stability are all good, can guarantee " safety, the homogeneous, stable, effective, controlled " of product quality.
Summary of the invention:
The invention provides a kind of method of quality control of fasudil hydrochloride injection; Fasudic hydrochloride has following chemical constitution: six hydrogen-1-(5-sulfonyl isoquinoline)-1 (H)-1; 4-diazepine hydrochloride; owing in the structure isoquinoline and diazepine group are arranged; make the product instability; therefore need in process of production finished product to be differentiated and assay timely, so that the product quality of control production run.Method of quality control of the present invention, simple, precision and accuracy height can be used in big production, and method of quality control of the present invention has strict specific aim at pharmaceutical preparation of the present invention, pharmaceutical preparation of the present invention, its prescription is composed as follows:
Every 1-10mL, hydrochloric Fasudil 15-60mg, solvent are water for injection.
Preferably:
Every 2mL, hydrochloric Fasudil 15-60mg, solvent are water for injection.
Its preparation method is as follows:
Get Fasudic hydrochloride, add the dissolving of injection water, be diluted to scale, degerming is filtered, embedding, and sterilization is stopped leakage in the roof, lamp inspection, packing.
The present invention be directed to the method for quality control of above preparation, at its characteristics and prescription of the present invention, we provide following method of quality control:
Method of quality control of the present invention may further comprise the steps:
The observation of proterties, the discriminating of content, the inspection of content is carried out assay to the composition that contains, and therefore, the main step of method of quality control of the present invention is:
One, the observation of proterties, step is:
This product is colourless or yellowish clear liquid.
Two, the discriminating of content, step is:
(1) gets this product 2ml, put evaporate to dryness in the water-bath (or near doing), get the about 5mg of residual solids.Put in the small test tube, the test tube mouth covers with the nickel hydroxide test paper, heating, and green nickel hydroxide test paper promptly shows black or gray corrosion.
(2) get solution under the assay item, measure, absorption maximum is arranged, minimal absorption is arranged at 250nm, 297nm wavelength place at 275nm, 312nm, 324nm wavelength place according to UV-VIS spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A).
Three, the inspection of content, step is:
The pH value should be 4.0-5.0 (two appendix VI of Chinese Pharmacopoeia version in 2005 H).
Color is got this product, compares with yellow No. 1 standard color solution (two appendix IXA first methods of Chinese Pharmacopoeia version in 2005), must not be darker.
Related substance is got this product, adds the moving phase dilution and makes the solution that contains 0.3mg among every 1ml, as need testing solution; Precision is measured 1ml, puts in the 100ml measuring bottle, is diluted to scale with moving phase, shakes up, in contrast solution.Measure according to high performance liquid chromatography (two appendix V of Chinese Pharmacopoeia version in 2005 D).With octadecylsilane chemically bonded silica is filling agent, and (with phosphoric acid adjust pH to 7.0)-methyl alcohol (15: 15) is moving phase with 1.0% triethylamine aqueous solution, and the detection wavelength is 275nm, and number of theoretical plate calculates by the Fasudic hydrochloride peak and generally is not less than 6600.The degree of separation of Fasudic hydrochloride peak and adjacent impurity peaks should meet the requirements.Get contrast solution 20 μ l and inject liquid chromatograph, regulate detection sensitivity, the peak height that makes the major component peak is the 10-20% of full scale, precision is measured need testing solution and each 20 μ l of contrast solution again, inject liquid chromatograph respectively, the record chromatogram is to 3 times of main peak retention time, in the need testing solution chromatogram if any impurity peaks, the peak area of single impurity must not be greater than 3/10 of contrast solution main peak area, main peak area each impurity peak area and that must not cross contrast solution.
Pyrogen is got this product, checks (two appendix XI of Chinese Pharmacopoeia version in 2005 D) in accordance with the law, and dosage should be up to specification by rabbit per kilogram of body weight injection 3mg.
The aseptic this product of getting is checked (two appendix XI of Chinese Pharmacopoeia version in 2005 H) in accordance with the law, should be up to specification.
Other should meet every regulation relevant under the injection item (two appendix IB of Chinese Pharmacopoeia version in 2005).
Four, the composition that contains is carried out assay, step is:
Get this product, add the solution that water is made hydrochloric approximately Fasudil 30 μ g among every 1ml,, measure absorbance at the wavelength place of 275nm according to UV-VIS spectrophotometry (two appendix IV of Chinese Pharmacopoeia version in 2005 A); It is an amount of that other gets the Fasudic hydrochloride reference substance, accurate claims surely, is dissolved in water and quantitatively is diluted to the solution of hydrochloric approximately Fasudil 30 μ g among every 1ml, measure with method, and calculating, promptly.
This product is the sterile water solution of Fasudic hydrochloride.Hydrochloric Fasudil (C
14H
17N
3O
2S.HCI) should be the 90.0-110.0% of labelled amount.
The above this product is a fasudil hydrochloride injection of the present invention.
The invention has the advantages that: method of quality control of the present invention has guaranteed that the quality inspection standard of preparation of the present invention can be than the qualitative character of effectively controlling preparation comprehensively, have accuracy and advance, can be used as the effective technology means of the stability of quality control and investigation technology.Be of great importance to improving the quality of products.
Embodiment:
Further specify the present invention by the following examples, but not as limitation of the present invention.
Embodiment 1:
The preparation of fasudil hydrochloride injection:
Get Fasudic hydrochloride 15g, add the dissolving of injection water, be diluted to the 1000ml scale, degerming is filtered, embedding, and sterilization is stopped leakage in the roof, lamp inspection, packing.
Embodiment 2:
The preparation of fasudil hydrochloride injection:
Get Fasudic hydrochloride 30g, add the dissolving of injection water, be diluted to the 1000ml scale, degerming is filtered, embedding, and sterilization is stopped leakage in the roof, lamp inspection, packing.
Embodiment 3:
The preparation of fasudil hydrochloride injection:
Get Fasudic hydrochloride 7.5g, add the dissolving of injection water, be diluted to the 1000ml scale, degerming is filtered, embedding, and sterilization is stopped leakage in the roof, lamp inspection, packing.
Embodiment 4,
The method of quality control of the fasudil hydrochloride injection of embodiment 1-3, step is as follows:
Observe proterties: this product is colourless or little yellow clear liquid.
Content is differentiated:
Sulfuryl (＞SO
2) differentiate
Get the about 2ml of this product, put in the water-bath and to steam driedly to being bordering on, get the about 5mg of residual solids, put in the microtest tube, the test tube mouth is put a small pieces nickel hydroxide test paper and is covered, and test tube heat a moment on spirit lamp, promptly apparent black of the nickel hydroxide test paper of green or gray corrosion.Sample all is positive reaction.
Ultraviolet spectrum
Get the need testing solution under this product assay item, draw the interior ultra-violet absorption spectrum of 400-200 scope according to spectrophotometric method (Chinese Pharmacopoeia appendix IV A), reference substance and clinical preceding sample and production sample all have absorption maximum at 275nm, 312nm, 324nm wavelength place, at 250nm, 297nm wavelength place minimal absorption are arranged.
Content is checked
The pH value
It is an amount of to get this product, presses two appendix VI of Chinese Pharmacopoeia H and measures, and clinical sample and production sample measurement result see Table 1.
Table 1. fasudil hydrochloride injection pH value measurement result
| Lot number | 971229 | ?971230 | ?971231 | ?20011201 | ?20011202 | ?20011203 |
| PH value | 4.60 | ?4.59 | ?4.66 | ?4.61 | ?4.65 | ?4.64 |
Solution colour
Get this product, press two appendix IXA of Chinese Pharmacopoeia, the first method inspection, sample determination the results are shown in Table 2.
Table 2. fasudil hydrochloride injection color detection result
| Lot number | 971229 | 971230 | 971231 | 20011201 | 20011202 | 20011203 |
| Color | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification | Up to specification |
Related substance is wherein checked
Adopt high performance liquid chromatography, measure with Self-control method.(second appendix VD of Chinese Pharmacopoeia).
Chromatographic condition performance liquid chromatographic column C
18ODS (5 μ granularity), [transferring pH value to 7.0 with phosphoric acid]-methyl alcohol [13: 17] is moving phase to 1.0% 3 amine aqueous solution, the detection wavelength is 275nm, flow velocity 0.6ml/min.
System suitability test is by above-mentioned conditional operation, and number of theoretical plate calculates by Fasudic hydrochloride and is not less than 3600.Main peak is up to specification with separating of each impurity peaks.
Determination method is got this product, adds moving phase and makes the solution that contains 0.3mg among every 1ml respectively, as need testing solution; Precision is measured 1ml, put in the 100ml measuring bottle, be diluted to scale with moving phase, shake up, solution in contrast, measure contrast solution 20 μ l, inject liquid chromatograph, regulate detection sensitivity, make the peak height at major component peak be about the 10-20% of full scale, other gets need testing solution 20 μ l, inject liquid chromatograph, the record chromatogram is to 3 times of the main peak retention time, in the chromatogram of need testing solution as show impurity peaks, measure each impurity peak area sum, with peak area (1.0%) comparison at contrast solution major component peak.Sample related substance check result sees Table 3.
Table 3. fasudil hydrochloride injection related substance check result
| Lot number | 971229 | ?971230 | ?971231 | ?20011201 | ?20011202 | ?20011203 |
| Related substance (%) | 0.12 | ?0.12 | ?0.12 | ?0.174 | ?0.139 | ?0.178 |
Clarity test
Get 200 of this product, by the regulation inspection of Ministry of Public Health's standard " clarity test detailed rules and regulations and criterion ", clinical sample and production sample are all up to specification.
Loading quantity inspection
Get 5 of this product, check that by Chinese Pharmacopoeia appendix IB relevant regulations clinical sample and production sample are all up to specification.
Sterility test
Get this product, the method (appendix XI H) of pressing under the Chinese Pharmacopoeia sterility test method item checks that clinical sample and production sample are all up to specification.
Assay
Get this product, add water and make the solution that the about saliferous of every ml is calculated Fasudil 30 μ g, it is an amount of that other gets the Fasudic hydrochloride reference substance, and accurate the title decides, and adds water and makes the contrast solution that solution is 30 μ g/ml.Get above-mentioned two kinds of solution,, measure absorbance log respectively, calculate, promptly at the 275nm place according to spectrophotometric method (Chinese Pharmacopoeia version appendix IV A).Sample determination the results are shown in Table 4.
Table 4.
| Lot number | 971229 | ?971230 | ?971231 | ?20011201 | ?20011202 | ?20011203 |
| Mean value (%) | 100.7 | ?99.27 | ?101.5 | ?93.57 | ?94.02 | ?94.02 |
Claims (1)
1. the detection method of a fasudil hydrochloride injection is characterized in that, described detection method may further comprise the steps:
The discriminating of content, step is:
(1) get this product 2ml, put evaporate to dryness in the water-bath, get the about 5mg of residual solids, put in the small test tube, the test tube mouth covers with the nickel hydroxide test paper, heating, and green nickel hydroxide test paper promptly shows black or gray corrosion,
(2) get solution under the assay item, measure, absorption maximum is arranged, minimal absorption is arranged at 250nm, 297nm wavelength place at 275nm, 312nm, 324nm wavelength place according to UV-VIS spectrophotometry, assay, step is:
Get this product, add the solution that water is made hydrochloric approximately Fasudil 30 μ g among every 1ml,, measure absorbance at the wavelength place of 275nm according to UV-VIS spectrophotometry; It is an amount of that other gets the Fasudic hydrochloride reference substance, accurate claims surely, is dissolved in water and quantitatively is diluted to the solution of hydrochloric approximately Fasudil 30 μ g among every 1ml, measure with method, and calculating, promptly.
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| CN101008637B true CN101008637B (en) | 2010-07-21 |
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Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102144971B (en) * | 2011-03-30 | 2012-10-03 | 天津红日药业股份有限公司 | Fasudil-containing oral spray or aerosol |
| CN102706997B (en) * | 2012-06-28 | 2014-07-16 | 武汉武药科技有限公司 | Detection method of fasudil hydrochloride-related substance |
| CN103901116B (en) * | 2012-12-26 | 2017-02-08 | 江苏万邦生化医药股份有限公司 | Detection analysis method for impurity homopiperazine in fasudil hydrochloride |
| CN103222953B (en) * | 2013-05-03 | 2014-03-12 | 成都苑东药业有限公司 | Fasudil hydrochloride injection composition and its preparation method |
| CN105866263B (en) * | 2016-03-24 | 2018-06-29 | 四川升和药业股份有限公司 | A kind of method of quality control of Fasudic hydrochloride |
| CN108593831B (en) * | 2018-05-08 | 2020-05-19 | 山东新华制药股份有限公司 | HPLC detection method of fasudil hydrochloride related substances |
| CN108398507A (en) * | 2018-05-08 | 2018-08-14 | 山东新华制药股份有限公司 | A kind of efficient liquid phase chromatographic analysis detection method of Fasudic hydrochloride impurity 5- isoquinolin methylmesylates |
| CN113752702B (en) * | 2021-10-13 | 2023-01-10 | 合肥京东方卓印科技有限公司 | Ink jet printing nozzle, cleaning method thereof and ink jet printing device |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6699508B1 (en) * | 1998-08-10 | 2004-03-02 | Asahi Kasei Pharma Corporation | Sustained release oral preparations of fasudil hydrochloride |
| CN1813762A (en) * | 2005-12-12 | 2006-08-09 | 天津红日药业股份有限公司 | Fasudic hydrochloride oral formulation |
-
2007
- 2007-01-11 CN CN2007100002261A patent/CN101008637B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6699508B1 (en) * | 1998-08-10 | 2004-03-02 | Asahi Kasei Pharma Corporation | Sustained release oral preparations of fasudil hydrochloride |
| CN1813762A (en) * | 2005-12-12 | 2006-08-09 | 天津红日药业股份有限公司 | Fasudic hydrochloride oral formulation |
Non-Patent Citations (1)
| Title |
|---|
| 张琳等.盐酸法舒地尔治疗急性脑梗死的临床研究.《实用心脑血管病杂志》.2006,第14卷(第5期),362、363. * |
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