Quantitative Analysis of Nitrosamine Impurities using LC-MS Methods from the United States Pharmacopeia General Chapter <1469>

Petra Lewits, Merck KGaA, Darmstadt, Germany (petra.lewits@merckgroup.com)
Tim Mueller, Merck Kgaa, Darmstadt, Germany
Patrik Appelblad, Merck Life Science As, Oslo, Norway

The United States Pharmacopeia (USP) published in December 2021 new procedures and methods as a response to unexpected detection of nitrosamines, classified as probable human carcinogens, such as N-nitrosodimethylamine (NDMA), in certain pharmaceutical active pharmaceutical ingredients (API), i.e., valsartan, ranitidine, etc. and corresponding final formulations. As a result, demand for nitrosamine analysis has rapidly increased worldwide. The list of concerned products manufactured from drug substances using specific synthetic routes has grown after extensive synthetic route assessments.

Chapter <1469> provide recommendations regarding; a) the creation of controls of nitrosamine levels to ensure their elimination or reduction; and b) analytical procedure performance characteristics for procedures to monitor nitrosamine levels (using two GC-MS and two LC-MS based procedures).

This poster discusses findings from work with establishing validated analytical protocols based on the new liquid chromatography high-resolution (HR) mass spectrometry (MS) method (procedure 1) and the new liquid chromatography MS/MS method (procedure 3) for the quantitative analysis of relevant nitrosamine impurities in pharmaceutical active pharmaceutical ingredients. 

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Short Biography of Presenting Author

Petra works with Chromatography for more than 35 years. She started her career in separation science in 1983 using several chromatographic methods, including HPLC, TLC, GC and Solid Phase Extraction (SPE), for food control in a governmental institution lab.
1986 she joined Merck´s pharmaceutical R&D and QC department (Merck KGaA in Darmstadt, Germany) were she development HPLC methods for R&D and QC of pharmaceutical API´s and formulations as well as for diet convenience foods.

From 1991 on she supported customers in different positions with technical and application related inquires in Europe as a sales specialist for HPLC instruments, technical support for Chromatography and complaint management.

Since 2002 she is a Global Product Manager for Analytical Chromatography (HPLC). From 2014 she was focusing on Thin-Layer Chromatography (TLC). Since April 2018 Petra has the global responsibility for analytical HPLC columns at Merck.