Analysis of Nitrosamines in APIs

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Event Overview:

In the summer of 2018, the pharmaceutical landscape for the manufacture of small molecules changed forever with the discovery of a small genotoxic compound in a batch of pharmaceuticals manufactured in China. Zhejiang Huahai pharmaceuticals produce valsartan, which is a prescription-only drug to treat high blood pressure and heart failure. It is a selective angiotensin II receptor blocker (ARB) which dilates blood vessels and so consequently reduces blood pressure. It is often given to patients directly after a heart attack. In performing the routine analysis, the quality control (QC) chemists found that there were approaching 60 ppm of N-nitrosodimethylamine (NDMA), which is high enough to cause one extra case of cancer in 500 patients. On the 5th July 2018, the European Medical Agency gave notice on their website that selected batches of valsartan were to be recalled with immediate effect. Since 2018, NDMA and other nitrosamines have been observed in a range of different pharmaceuticals.

This webinar will begin with a brief overview of nitrosamine formation, the chronological developments since 2018 and impacts on the regulatory landscape. We will then focus on the development of a LC-MS/MS method for the analysis of eight targeted nitrosamines. The method development will investigate how careful analysis of the physiochemical data can allow a better separation to be developed, in particular how the pH can affect both peak shape and retention time of individual nitrosamines. The impact that the use of the mass spectrometer as a detector can have on the integrity of the analytical data will be thoroughly investigated. This will include insight into the impact that ion suppression can have when analyzing real samples and also the impact that different calibration models have on the determination of a working LOD. The presentation will be summarized with a review of the data produced from a validatable method that can be applied to the analysis of nitrosamines in an active API. Potential issues arising from coelution of NMDA with DMF will be discussed, along with potential solutions, including an assessment of alternative column selectivity.

Key Learning Objectives:

• Learn the importance of testing for nitrosamine concentrations in pharmaceuticals
• Understand the regulatory landscape that has evolved to deal with this range of genotoxins
• Review examples of nitrosamine analysis
• Learn key aspects of effective method development for LC–MS methods for nitrosamine analysis

Who Should Attend?

• Researchers involved in the study and analysis of nitrosamines

Speakers

Matt James, Ph.D.
Senior Research Scientist
Avantor

Matt James is a Senior Research Scientist at Avantor Sciences. Matt gained his PhD at University of Bristol, working on the analysis of archaeological samples and also worked within the pharmaceutical industry for a year. Over the last 11 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 by LC-MS/MS. Matt has co-authored seven peer reviewed articles and presented work at several conferences.

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