Determination of Dimethylamine and Nitrite in Pharmaceuticals by Ion Chromatography to Assess the Likelihood of Nitrosamine Formation

Since July 2018 several drugs have been recalled due to contamination with N-nitrosodimethylamine (NDMA), a probable human carcinogen. Dimethylamine (DMA) and nitrite are precursors in the formation of NDMA.

Ion chromatography (IC) methods were developed for the determination of these two precursors in drug substances and drug products. Dimethylamine was determined by a cation exchange separation with suppressed conductivity detection using one of two methods, depending on the chemical nature of the drug substance. Nitrite was determined by coupling an anion exchange separation with UV absorbance detection. The developed methods were successfully applied to DMA and nitrite determinations in five drug products including metformin, losartan, ranitidine, Nytol, and Benadyrl, and two drug substances (APIs), losartan potassium and metformin hydrochloride. Some samples contained nitrite and DMA at detectable levels. The developed methods should be useful for the rapid screening and quantification of nitrite and DMA in pharmaceuticals and in-process sample to assess the likelihood of NDMA formation. The methods for DMA should be applicable to other amines to assess the likelihood of the formation of other nitrosamines in pharmaceutical products.

Key learning objectives:

• Advantages of ion chromatography for the evaluation/characterization of pharmaceutical samples
• Details of IC methods for the determination of two NDMA precursors (dimethylamine and nitrite) in pharmaceutical samples
• How to develop IC methods to determine an amine in a pharmaceutical sample

Who should attend:

• Analysts, team leaders, data integrity specialist, QA auditors & lab managers in Pharma analytical testing environments
• Scientists and chemists at analytical science testing laboratories, CDMOs, or pharmaceutical manufacturers
• Analysts and companies performing nitrosamine analysis in drug products and drug substances

Presenter: Jingli Hu (Senior Applications Chemist, Thermo Fisher Scientific)

Jingli is a Senior applications chemist at Thermo Fisher Scientific in Sunnyvale, CA. She has been with Thermo Fisher Scientific for about five years. At Thermo Fisher Scientific, she is currently focusing on ion chromatography applications within the food, environmental and biopharma markets. Prior to joining Thermo Fisher Scientific, she has seven years of R&D lab experience in food and pharmaceutical industries.