Quantitation of 5 NSA in Metformin API as per proposed USP General Chapter Procedure-4 by GC-MS/MS

User Benefits

- A GC-MS/MS method for the determination of 5 Nitrosamines in Metformin API - The GCMS-TQ 8050 NX system easily meets the criteria as per the USP guidance on Nitrosamines

Introduction

Overview : The presence of Nitrosamine (NSA) as impurity has been detected recently in several drug substances and drug products. In 2018, N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA) were detected in some Valsartan Active Pharmaceutical Ingredients (API) and Finished Dosage Form (FDF). This led to an ongoing investigation to check presence of NSA in pharmaceutical substances and products. One such drug is Metformin; it is used to control high blood sugar observed in patients suffering from type 2 diabetes. What are NSA? : NSA are organic compounds of the chemical structure R₂N−N=O, where R is usually an alkyl group. These compounds are listed as Class 1 mutagens in ICH M7: Assessment and Control of DNA Reactive (Mutagenic) Impurities in Pharmaceuticals to limit potential carcinogenic risk. As a result of the significant toxicity associated with these impurities, it is recommended to take steps to control and limit their presence in pharmaceutical materials. USP General Chapter <1469> : To protect patients from the adverse effects of NSA as impurities in drug products, Unites States Pharmacopeia (USP) has proposed a new general chapter <1469>. This chapter is aligned with current scientific and regulatory approaches developed to ensure the appropriate control of NSA in pharmaceuticals. The proposed chapter comprises of 4 procedures for NSA determination in API and FDF. However, this application note aims to replicate the procedure-4 for quantitation of following 5 NSA in Metformin API using Shimadzu GCMS-TQ 8050 NX system with AOC-20i Plus autosampler. 1) N-nitrosodimethylamine (NDMA) 2) N-nitrosodiethylamine (NDEA) 3) N-nitrosoethylisopropylamine (NEIPA) 4) N-nitrosodiisopropylamine (NDIPA) 5) N-nitrosodibutylamine (NDBA)

May 16, 2022 GMT