氯氮平片质量分析与研究
发布时间：2019-04-18 23:50
【摘要】：目的:对国内不同厂家生产的氯氮平片进行法定标准检验及探索性研究,对该品种的质量状况作出总体分析和评价。方法:法定标准检验依据《中国药典》2010年版二部,进行了全项检验。探索性研究参照美国药典USP35版氯氮平原料药项下有关物质检测方法,采用HPLC法检测,结合UPLC-MS,对不同企业提供的氯氮平原料药及国内制剂进行杂质研究,与进口原料药及制剂进行杂质谱比对;采用HPLC法测定了18个企业的46批样品在4种不同p H值介质中的溶出曲线,并采用f2因子与参比制剂TEVA公司生产的氯氮平片溶出曲线进行比较;对25 mg规格的氯氮平片测定了含量均匀度;用光散射的湿法测定进行粒度分析;采用DSC、X衍射进行原料晶型研究;进行溶剂残留、重金属及有害元素的检测,以及制剂与包材稳定性考察;建立氯氮平片近红外光谱快速检验模型;建立了快速液相定量方法。结果:法定标准检验:在199批样品中,全检合格198批,有1批样品重量差异项目不合格,不合格率为0.5%。探索性研究:有关物质研究表明,氯氮平原料药的国内外杂质谱基本一致,《中国药典》2010年版有关物质检查方法不能有效分离并控制单个特殊杂质。溶出曲线考察,仅有少数的样品在4种介质中溶出行为与参比制剂相似,多数样品溶出行为与参比制剂存在差异。粒度研究表明国产原料药平均粒径远远大于进口原料药。晶型研究未见不同晶型及结晶水情况。未检出溶剂残留;原料药及制剂的重金属和有害元素含量远远低于药典规定;产品在高温高湿条件下比较稳定;现有外包材能够满足药品储存运输的要求。共建立28个氯氮平片近红外光谱快速检验模型。建立了氯氮平片的快速液相定量分析方法。结论:氯氮平片质量总体较好,未发现违规违法生产问题。现行质量标准基本可行,个别项目检查方法需要改进。
[Abstract]:Aim: to analyze and evaluate the quality of clozapine tablets produced by different manufacturers in China. Methods: according to part two of Chinese Pharmacopoeia (2010 edition), the legal standard test was carried out. According to the related substances detection methods of clozapine in USP35 version of US Pharmacopoeia, the HPLC method and UPLC-MS, were used to study the impurities of clozapine raw materials and domestic preparations provided by different enterprises. The impurity spectra were compared with imported raw materials and preparations. The dissolution curves of 46 batches of samples from 18 enterprises in four media with different pH values were determined by HPLC, and the dissolution curves of clozapine tablets produced by reference agent TEVA were compared with f2 factor. The content uniformity of 25 mg clozapine tablets was determined, the particle size analysis was carried out by wet method of light scattering, the crystal structure of raw materials was studied by DSC,X diffraction, and the content uniformity of clozapine tablets was determined by DSC,X diffraction. The determination of solvent residues, heavy metals and harmful elements, as well as the stability of preparation and coating, the rapid detection model of near infrared spectrum of clozapine tablets and the quantitative method of rapid liquid phase were established. Results: in 199 batches of samples, 198 batches of total samples were qualified, one batch of sample weight difference items were not qualified, and the unqualified rate was 0.5%. Exploratory research shows that the impurity spectra of chloro-nitrogen plain drugs are basically the same at home and abroad, and the methods for the determination of related substances in the 2010 edition of Chinese Pharmacopoeia cannot effectively separate and control individual special impurities. The dissolution curve showed that only a few of the samples were similar to the reference formulation in four media, and the dissolution behavior of most samples was different from that of the reference preparation. Particle size studies show that the average particle size of domestic raw materials is much larger than that of imported raw materials. There are no different crystal forms and crystal water in the study of crystal form. Solvent residues were not detected; the contents of heavy metals and harmful elements in raw drugs and preparations were far lower than those prescribed in pharmacopoeia; the products were stable under high temperature and humidity; and the existing outsourcing materials could meet the requirements of drug storage and transportation. A total of 28 fast detection models of clozapine tablets by near infrared spectroscopy (NIR) were established. A rapid liquid phase quantitative analysis method for clozapine tablets was established. Conclusion: clozapine tablets were of good quality and no illegal production was found. The current quality standards are basically feasible, and individual inspection methods need to be improved.
【作者单位】： 云南省食品药品检验所;
【基金】：2013年国家药品计划抽验品种、中央补助地方经费项目(编号110)
【分类号】：R917
[Abstract]:Aim: to analyze and evaluate the quality of clozapine tablets produced by different manufacturers in China. Methods: according to part two of Chinese Pharmacopoeia (2010 edition), the legal standard test was carried out. According to the related substances detection methods of clozapine in USP35 version of US Pharmacopoeia, the HPLC method and UPLC-MS, were used to study the impurities of clozapine raw materials and domestic preparations provided by different enterprises. The impurity spectra were compared with imported raw materials and preparations. The dissolution curves of 46 batches of samples from 18 enterprises in four media with different pH values were determined by HPLC, and the dissolution curves of clozapine tablets produced by reference agent TEVA were compared with f2 factor. The content uniformity of 25 mg clozapine tablets was determined, the particle size analysis was carried out by wet method of light scattering, the crystal structure of raw materials was studied by DSC,X diffraction, and the content uniformity of clozapine tablets was determined by DSC,X diffraction. The determination of solvent residues, heavy metals and harmful elements, as well as the stability of preparation and coating, the rapid detection model of near infrared spectrum of clozapine tablets and the quantitative method of rapid liquid phase were established. Results: in 199 batches of samples, 198 batches of total samples were qualified, one batch of sample weight difference items were not qualified, and the unqualified rate was 0.5%. Exploratory research shows that the impurity spectra of chloro-nitrogen plain drugs are basically the same at home and abroad, and the methods for the determination of related substances in the 2010 edition of Chinese Pharmacopoeia cannot effectively separate and control individual special impurities. The dissolution curve showed that only a few of the samples were similar to the reference formulation in four media, and the dissolution behavior of most samples was different from that of the reference preparation. Particle size studies show that the average particle size of domestic raw materials is much larger than that of imported raw materials. There are no different crystal forms and crystal water in the study of crystal form. Solvent residues were not detected; the contents of heavy metals and harmful elements in raw drugs and preparations were far lower than those prescribed in pharmacopoeia; the products were stable under high temperature and humidity; and the existing outsourcing materials could meet the requirements of drug storage and transportation. A total of 28 fast detection models of clozapine tablets by near infrared spectroscopy (NIR) were established. A rapid liquid phase quantitative analysis method for clozapine tablets was established. Conclusion: clozapine tablets were of good quality and no illegal production was found. The current quality standards are basically feasible, and individual inspection methods need to be improved.
【作者单位】： 云南省食品药品检验所;
【基金】：2013年国家药品计划抽验品种、中央补助地方经费项目(编号110)
【分类号】：R917
【相似文献】
相关期刊论文 前10条
1 吴岚;;高效液相色谱法测定人血浆中氯氮平浓度[J];岳阳职业技术学院学报;2007年04期
2 刘伟忠;陈清霞;黄伟侨;吕永丰;温预关;王广发;;高效液相色谱法同时测定人血浆中氯氮平与氟西汀的浓度[J];广东药学院学报;2011年03期
3 谭晓辉;尉志文;于晓巍;，
本文编号：2460397
本文链接：https://www.wllwen.com/yixuelunwen/yiyaoxuelunwen/2460397.html
最近更新
教材专著
