Abstract

HIGHLY SENSITIVE AND ROBUST DETERMINATION OF 12 NITROSAMINE IMPURITIES IN VALSARTAN DRUG PRODUCT

*Varun Khali, Jyoti Rawat

Abstract

Nitrosamine impurities belong to a class of probable carcinogens that are present in various pharmaceutical products and are also called as pharmaceutical contaminants. In this study 12 out of the most significant nitrosamine impurities were taken for quantitative determination in Valsartan tablet formulation that are commercially available in multiple strengths of 40mg, 80mg and 320mg etc. For acceptable intake and other relevant information, EMA and FDA guidelines were referred. The experiments in this work were performed as per current requirements in analytical chemistry where highly sophisticated analytical techniques are required such as LCMS/ MS to quantify trace levels of nitrosamine impurities in drug products. The results show that an appropriate method is required to be developed and validated for an accurate and reliable detection of nitrosamine impurities and that is what is performed in this study. Depending upon the Acceptable intake of 26.5 ng/day and 320mg of Maximum daily dose for Valsartan, 0.083 ppm (parts per million) was the specification limit. This kind of methodology supports routine product testing to ensure product safety and regulatory compliance.

Keywords: Nitrosamines (NSA), Nitroso drug substance related impurities (NDSRIs), analytical chemistry, LC-MS/MS, pharmaceutical contaminants, carcinogens, acceptable intake (AI), maximum daily dose (MDD).