Regulatory Updates and Analytical Methodologies for Nitrosamine Impurities Detection in Sartans, Ranitidine, Nizatidine, and Metformin along with Sample Preparation Techniques

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

Keywords:

• GC-MS-HS-AS
• HPLC
• LC-HRMS
• LC-MS/MS
• LLE
• NDEA
• NDMA
• SPE

Acknowledgment

Authors of the manuscript appreciate the infrastructure and basic facilities support provided by Director, NIPER, Guwahati, in this regard.

Disclosure statement

No potential conflict of interest was reported by the authors.