Analysis of N-Nitrosodimethylamine (NDMA) & N-Nitrosodiethylamine (NDEA) in pharmaceutical substance by HSGCMS

Introduction

N-Nitrosodimethylamine (NDMA) & N- Nitrosodiethylamine (NDEA) are simplest of Dialkylnitrosamines. They are continued to be released as a by-product and contaminant from various industries and from municipal wastewater treatment plants. Major releases of NDMA, NDEA have been from the manufacture of pesticides, rubber tires, alkyl amines, and dyes. Similarly, these compounds are produced as a byproduct in the manufacturing of Active Pharmaceutical Ingredients (API’s). These compounds are classified as a Group 2A carcinogen (probable human carcinogen) by the World Health Organization. Recently, some drug products were discovered to have been contaminated with NDMA & NDEA. It is believed to have been introduced into the finished products as a result of the manufacturing process of the drug substance. This contamination, was far exceeding the regulatory exposure limits specific to drug products. Consequently, medical agencies across Europe as well as the US Food and Drug Administration (USFDA) withdrew all affected drug products from the market. Hence it is very essential to have a sensitive, accurate, reliable & robust method by using suitable analytical technique. The USFDA Office of Testing and Research (OTR) has developed an Headspace Gas Chromatography Mass Spectrometry (HSGCMS) method to detect the presence of NDMA in drug substance. In this experiment the pharmaceutical API’s namely Valsartan, Losartan & Olmesartan-Medoximil prone to contamination with NDMA and NDEA is analyzed by referring USFDA OTR HSGCMS method.

December 18, 2019 GMT