难溶性原料药、辅料、制剂细菌内毒素检查方法的研究进展

doi:10.19803/j.1672-8629.20230423

摘要/Abstract

摘要： 目的总结药典及近10年相关文献中有关难溶性样品检测方法的建立思路,为难溶性原料药、辅料、制剂的内毒素检查研究提供借鉴。方法重点对药典及国内文献中难溶性样品的内毒素限值确定、检查方法、溶解方法、排除干扰的思路进行详细分析与论述,尤其对有机溶剂的选择重点阐述。结果及结论 难溶性样品细菌内毒素检测方法建立的难点在于寻找合适的溶剂及排除干扰,溶解方法考虑有机溶剂、非有机溶剂、物理方法,排除干扰的方法考虑调节pH、补充二价阳离子、使用抗增液、分散剂等思路,以期为后续研究提供思路。

关键词: 原料药, 辅料, 制剂, 细菌内毒素, 鲎试剂, 难溶性, 方法学, 质量安全, 排除干扰

Abstract: Objective To summarize the ideas behind test methods established for insoluble samples in the Chinese Pharmacopoeia and related literature in China over the past 10 years, and to provide reference for endotoxin detection of insoluble APIs, excipients and preparations. Methods The determination of endotoxin limits, inspection methods, dissolution methods, and strategies for excluding interferences in domestic literature on insoluble samples were analyzed by focusing on the selection of organic solvents. Results and conclusion The difficulty in establishing a method for the detection of bacterial endotoxin in insoluble samples lies in the search for suitable solvents and the elimination of interferences. Dissolution methods involve organic solvents, non-organic solvents and physical methods, while the elimination of interferences involves the adjustment of pH, the supplementation of divalent cations, and the use of antiproliferative fluids and dispersants. This study is expected to inspire ideas for subsequent research.

Key words: raw materials, excipients, preparations, bacterial endotoxin, TAL, insolubility, methodology, quality safety, elimination of interference

中图分类号:

R927.1

张晨雪, 裴宇盛, 蔡彤. 难溶性原料药、辅料、制剂细菌内毒素检查方法的研究进展[J]. 中国药物警戒, 2024, 21(3): 273-279.

ZHANG Chenxue, PEI Yusheng, CAI Tong. Research progress in bacterial endotoxin test methods for insoluble raw materials, excipients and preparations[J]. Chinese Journal of Pharmacovigilance, 2024, 21(3): 273-279.

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