{"title":"GC-MS和LC-MS技术在原料药中胺类物质直接分析中的应用","authors":"A. Witkowska, E. Stolarczyk, A. Groman, M. Zezula","doi":"10.32383/appdr/156083","DOIUrl":null,"url":null,"abstract":"Organic volatile chemicals such as amines are often not completely removed by practical manufacturing techniques and consequently their low levels are present in most pharmaceuticals. Based on good manufacturing practices and for the safety of the patients the level of hazardous for human health amines in pharmaceuticals have to be strictly controlled. Moreover, analysis of volatile amines in drug product has become recently an emerging topic of interest for analytical chemists since such residual impurities as: secondary amines, tertiary amine and other amine derivatives (in certain condition) have been reported to be a precursors of carcinogenic N-nitrosamines (NAs). In this study we present five new methods for control of such amines as: tert-butylamine (TBA), pyrrolidine, 4-fluoroaniline (4-FA), diisopropyl-ethylamine (DIPEA) and tetrabutylammonium hydrogensulfate (TBAHS) in pharmaceutical active ingredients (APIs) using GC-MS and LC-MS techniques. The validations results clearly demonstrate that the analytical procedures are suitable for their intended purpose. All revealed validations results meet the requirements of the ICH Q2R1 validation guidelines and the Q3A R2 guideline for residual impurities.","PeriodicalId":7147,"journal":{"name":"Acta poloniae pharmaceutica","volume":" ","pages":""},"PeriodicalIF":0.4000,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Application of GC-MS and LC-MS techniques for direct analysis of amines in pharmaceutical substances\",\"authors\":\"A. Witkowska, E. Stolarczyk, A. Groman, M. Zezula\",\"doi\":\"10.32383/appdr/156083\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Organic volatile chemicals such as amines are often not completely removed by practical manufacturing techniques and consequently their low levels are present in most pharmaceuticals. Based on good manufacturing practices and for the safety of the patients the level of hazardous for human health amines in pharmaceuticals have to be strictly controlled. Moreover, analysis of volatile amines in drug product has become recently an emerging topic of interest for analytical chemists since such residual impurities as: secondary amines, tertiary amine and other amine derivatives (in certain condition) have been reported to be a precursors of carcinogenic N-nitrosamines (NAs). In this study we present five new methods for control of such amines as: tert-butylamine (TBA), pyrrolidine, 4-fluoroaniline (4-FA), diisopropyl-ethylamine (DIPEA) and tetrabutylammonium hydrogensulfate (TBAHS) in pharmaceutical active ingredients (APIs) using GC-MS and LC-MS techniques. The validations results clearly demonstrate that the analytical procedures are suitable for their intended purpose. All revealed validations results meet the requirements of the ICH Q2R1 validation guidelines and the Q3A R2 guideline for residual impurities.\",\"PeriodicalId\":7147,\"journal\":{\"name\":\"Acta poloniae pharmaceutica\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":0.4000,\"publicationDate\":\"2023-01-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta poloniae pharmaceutica\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.32383/appdr/156083\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta poloniae pharmaceutica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.32383/appdr/156083","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Application of GC-MS and LC-MS techniques for direct analysis of amines in pharmaceutical substances
Organic volatile chemicals such as amines are often not completely removed by practical manufacturing techniques and consequently their low levels are present in most pharmaceuticals. Based on good manufacturing practices and for the safety of the patients the level of hazardous for human health amines in pharmaceuticals have to be strictly controlled. Moreover, analysis of volatile amines in drug product has become recently an emerging topic of interest for analytical chemists since such residual impurities as: secondary amines, tertiary amine and other amine derivatives (in certain condition) have been reported to be a precursors of carcinogenic N-nitrosamines (NAs). In this study we present five new methods for control of such amines as: tert-butylamine (TBA), pyrrolidine, 4-fluoroaniline (4-FA), diisopropyl-ethylamine (DIPEA) and tetrabutylammonium hydrogensulfate (TBAHS) in pharmaceutical active ingredients (APIs) using GC-MS and LC-MS techniques. The validations results clearly demonstrate that the analytical procedures are suitable for their intended purpose. All revealed validations results meet the requirements of the ICH Q2R1 validation guidelines and the Q3A R2 guideline for residual impurities.
期刊介绍:
The international journal of the Polish Pharmaceutical Society is published in 6 issues a year. The journal offers Open Access publication of original research papers, short communications and reviews written in English, in all areas of pharmaceutical sciences. The following areas of pharmaceutical sciences are covered: Analysis, Biopharmacy, Drug Biochemistry, Drug Synthesis, Natural Drugs, Pharmaceutical Technology, Pharmacology and General.
A bimonthly appearing in English since 1994, which continues “Acta Poloniae Pharmaceutica”, whose first issue appeared in December 1937. The war halted the activity of the journal’s creators. Issuance of “Acta Poloniae Pharmaceutica” was resumed in 1947. From 1947 the journal appeared irregularly, initially as a quarterly, then a bimonthly. In the years 1963 – 1973 alongside the Polish version appeared the English edition of the journal. Starting from 1974 only works in English are published in the journal. Since 1995 the journal has been appearing very regularly in two-month intervals (six books a year). The journal publishes original works from all fields of pharmacy, summaries of postdoctoral dissertations and laboratory notes.