Abstract

Nitrosamine impurities have been detected in various pharmaceutical products in recent days. Various sartans, ranitidine, nizatidine, and metformin have been recalled from the markets due to the high limit of nitrosamine impurities. This review aims to provide a brief overview of nitrosamine impurities, detection methods in detail, mechanism of action of nitrosamine impurities, sample preparation techniques, and regulatory limits. Numerous reported nitrosamine impurities also have been discussed with chemical structure. Various detection methods including LC-MS/MS, GC-MS-HS, and HPLC for nitrosamine impurities along with sartans, ranitidine, nizatidine, and metformin are being discussed in this review article. Various sample preparation techniques such as solid-phase extraction, liquid–liquid extraction, and rapid-fire techniques have also been discussed. This review will provide the detail information to the analytical manpower working in various quality control laboratories as well as in research organizations.

• Highlights

• Detection of nitrosamine (NA) impurities in drug substances as well as finished products.

• HPLC, LC-MS/MS, and GC-MS/HS/AS discussed for the quantification

• Solid-phase extraction, liquid–liquid extraction, and rapid-fire method for NA sample preparation

• Mechanistic approach for nitrosamine formation and its removal strategies

• Regulatory limits for NA impurities incorporated

摘要

最近几天在各种药品中检测到亚硝胺杂质。由于亚硝胺杂质含量过高，各种沙坦类、雷尼替丁、尼扎替丁和二甲双胍已从市场召回。本综述旨在简要概述亚硝胺杂质、详细的检测方法、亚硝胺杂质的作用机制、样品制备技术和监管限制。许多报道的亚硝胺杂质也与化学结构进行了讨论。本综述文章讨论了各种检测方法，包括 LC-MS/MS、GC-MS-HS 和 HPLC，用于检测亚硝胺杂质以及沙坦类、雷尼替丁、尼扎替丁和二甲双胍。多种样品制备技术，如固相萃取、液-液萃取、还讨论了速射技术。该审查将为在各种质量控制实验室以及研究机构工作的分析人员提供详细信息。

• 强调

• 检测原料药和成品中的亚硝胺 (NA) 杂质。

• 讨论了定量的 HPLC、LC-MS/MS 和 GC-MS/HS/AS

• 用于 NA 样品制备的固相萃取、液-液萃取和速射法

• 亚硝胺形成的机理方法及其去除策略

• 纳入的 NA 杂质的监管限制