잔류용매 모니터링에 관한 연구 (II) - 원료의약품 중 잔류용매 (Class 3,4) 모니터링
The study on residual solvents (II) ; Monitoring of residual solvents (Class 3,4) in pharmaceutical raw material
보고서 정보
주관연구기관
랩프런티어(주) LabFrontier Co. Ltd
연구책임자
박종세
발행국가
대한민국
언어
한국어
발행년월
2002-12
주관부처
식품의약품안전청
사업 관리 기관
랩프런티어(주) LabFrontier Co. Ltd
등록번호
TRKO200300001460
DB 구축일자
2013-04-18
초록▼
본 연구에서는 ICH가이드라인 중 Class 3, 4에 해당하는 잔류유기용매들의 분석방법으로서 USP 25, EP 4 및 기타 문헌들에서 가장 많이 채택하고 있는 CC-Headspace Sampler (GC-HSS) 방법 및 직접주입방법을 검증하였다. 해외 문헌 및 USP 25, EP 4등의 공정서에 나타난 잔류유기용매의 분석방법 및 시료전처리방법 등을 검토하고, 현재 국내의 일부 제약회사에서 사용되고 있는 잔류유기용매 분석방법을 기초로 하여 최적의 분석방법을 검토하였다. 또한 한국제약협회 및 한국의약품수출입협회의 자료에 따
본 연구에서는 ICH가이드라인 중 Class 3, 4에 해당하는 잔류유기용매들의 분석방법으로서 USP 25, EP 4 및 기타 문헌들에서 가장 많이 채택하고 있는 CC-Headspace Sampler (GC-HSS) 방법 및 직접주입방법을 검증하였다. 해외 문헌 및 USP 25, EP 4등의 공정서에 나타난 잔류유기용매의 분석방법 및 시료전처리방법 등을 검토하고, 현재 국내의 일부 제약회사에서 사용되고 있는 잔류유기용매 분석방법을 기초로 하여 최적의 분석방법을 검토하였다. 또한 한국제약협회 및 한국의약품수출입협회의 자료에 따라 2001년 국내생산 및 수입된 시중에 유통되는 국산 원료의약품 22품목과 수입원료 의약품 18품목에 대하여 잔류유기용매를 모니터링 하였다. ICH에서 허용된 기준 이상의 잔류유기용매가 검출 된 원료의약품에 대해서는 GC-MS를 통하여 그 종류를 최종적으로 확인하였다.
Abstract▼
Synthesis and purification of pharmaceutical raw materials involves many kinds of organic solvents, which are usually removed by several steps of evaporation. Some solvents, however, may remain in the final product, if an improper evaporation method is chosen for those solvents. These residual solve
Synthesis and purification of pharmaceutical raw materials involves many kinds of organic solvents, which are usually removed by several steps of evaporation. Some solvents, however, may remain in the final product, if an improper evaporation method is chosen for those solvents. These residual solvents possibly change the physical or chemical characteristics such as the crystal structure or solubility of the raw material, then make the quality of the drug unreliable and uncontrollable. Moreover the residual solvents can act as narcotics, neurotoxigens, carcinogens and environmental pollutants. International Conference of Harmonization(ICH) had made a regulation on the kind and quantity limit of the important residual solvents through the Q3C Residual Solvents section in the Quality Regulation part. The United States Pharmacopoeia 25(USP 25) and European Pharmacopeia 4(EP 4) have adopted this ICH guideline for their own residual solvents regulation. Exporting the pharmaceutical raw materials and pharmaceutical products to these nations requires the quality control data for the kind and quantity limit of the residual solvents in the exports according to each pharmacopeia. Large amount of the raw materials fur the domestic pharmaceutical products is now imported from China, India, and etc. The problem is that the residual solvents in these cheap imports are not properly regulated yet. It is very necessary to prepare a resonable regulation on the kind and quantity limit of the residual solvents in both the imported and the domestically producted pharmaceutical raw materials and pharmaceutical products. We compared the analytical methods for the residual solvents presented by ICH guidelines, USP 25, EP 4 and other references on residual solvents of Class 3 and 4 residual solvents by ICH classification. The sample preparation methods and the gas chromatography flame ionization detector(GC-FID) methods with the static headspace autosampler are investigated to propose an optimized analytical method. The optimized method was validated according to the ICH guidelines, and the precision and accuracy results satisfied the USP 25 regulation. This method was applied to the 22 kinds of domestically producted and 18 kinds of imported pharmaceutical raw materials for the determination of the residual solvents. The gas chromatography mass spectrometry(GC-MS) was used to identify the ever detected one. No significant residual solvent was detected in all the raw materials from domestic and imported raw materials.
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