Quantitation of 8 Nitrosamines in 12 Different Solvents by LC-MS/MS System

User Benefits

・A single LC-MS/MS method for the determination of 8 nitrosamines in 12solvents. ・It easily meets current regulatory requirement i.e. 0.03 ppm for the nitrosamines　[EMA(Europian Medical Agency)]. ・The same method can be extended for the other solvents which are not mentioned in the application note.

Introduction

In June 2018, the American Food and Drug Administration (FDA) was informed of the presence of an impurity identified as N-nitrosodimethylamine (NDMA) in the ARB valsartan. Through investigation, the Agency determined that numerous valsartan and a few other ARB drug products from different manufactures contained unacceptable levels of nitrosamines. The drug product manufacturers voluntarily recalled the affected batches of these drug products, which led to a drug shortage in some of the affected products. In addition, the FDA evaluated processes that use common amines in API synthesis and learned that common synthetic pathways could also introduce other types of nitrosamine impurities besides NDMA. General Root Causes for the Presence of Nitrosamine Impurities in APIs: 1)Source of secondary, tertiary and quaternary amines that can form nitrosamines. 2)Contamination of raw material used for the manufacturing of APIs leads to the addition of nitrosamines. 3)Recovery solvents, catalysts and reagents as source of contaminations. A manufacturing site may produce the same API more than one synthetic process that uses common solvents. If any of those synthetic processes produce nitrosamines or contains precursor amines, the solvents sent for recovery are at risk. The use of recovered solvents that are comingled from different processes or across manufacturing lines without control and monitoring can introduce nitrosamine impurities. If a recovered solvent is contaminated in this way and then used to manufacture an API, the API will be contaminated even if the synthetic route is not normally susceptible to nitrosamine formation. Traditionally the GCMS is a preferred and simple technique to determine the nitrosamines in solvents. However, NMBA can only be detected by LCMS technique. In this application note an LCMS method has been developed for the simultaneous determination of 8 nitrosamines in 12 different solvents.

September 5, 2023 GMT