LCMS/MS Method Considerations for Nitrosamine Analysis in APIs

Detecting nitrosamines is a complex challenge, but new LC-MS/MS methods are making it easier to achieve accuracy and confidence in results. Join us to discover proven strategies that overcome common interferences and deliver reliable detection at regulatory limits.

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Event Overview:

Detection of mutagenic nitrosamines in drug substance and product is an area of global concern. The polar nature and low molecular weight of some nitrosamines makes achieving chromatographic retention by LC challenging and presents possibilities for interference from other low molecular weight impurities.
During development of an LC-MS/MS method for eight target nitrosamines in API, significant over-quantification of N-nitrosodimethylamine (NDMA) was observed due to isobaric interference from co-eluting DMF. Several stationary phase chemistries were found to provide enhanced retention and separation of NDMA and DMF. Two alternative methods were developed and both demonstrated excellent linearity (R2 ≥ 0.99), accuracy (93.3 to 109.1%) and precision (%RSD 0.3 to 9.5%) with limits of detection ranging from 0.02 to 0.55 ppb with respect to drug substance (0.04 to 1.5 pg on column), significantly lower than limits specified by regulatory authorities. The improved chromatographic selectivity successfully improved NDMA quantification accuracy in the presence of DMF.

Key Learning Objectives:

• High-sensitivity targeted reversed-phase LC-MS analysis of small molecule nitrosamines can be effectively achieved.
• How isobaric interference from DMF was observed for NDMA.
• Why metformin drug substance analysis has additional challenges.

Who Should Attend:

• Laboratory professionals, researchers, scientists, and lab managers involved in analytical chemistry, quality control, drug discovery, environmental testing, and other applications utilizing LC-MS technology.
• Pharma, R&D labs, Biotech, Analytical specialty labs, Academia

Speaker:

Matt James is a Senior Research Scientist at Avantor Sciences. Matt gained his PhD at University of Bristol and over the last 15 years, he has worked within the Technical Support, Applications and R&D teams within Hichrom, now part of Avantor. Recent focuses have been HPLC/UHPLC method transfer and translation, the use of solid core phases, development of next generation LC stationary phases and the development of LC methods for key applications, such as the analysis of nitrosamines and PFAS by LC-MS/MS.

Register Free: https://www.chromatographyonline.com/lcgc_w/method_considerations