N-nitrosodimethylamine (NDMA) is a pharmaceutical Class 1 impurity and has been identified as a probable human carcinogen. The source of NDMA impurities in active pharmaceutical ingredients (APIs) varies, and can be introduced at a number of points in the API manufacturing process. NDMA impurities have been observed in the drug ranitidine, an H2 (histamine-2) blocker commonly used to relieve and prevent heartburn. Multiple regulatory bodies, including the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA), have established interim acceptable daily intake limits for NDMA in ranitidine at 96 ng per day.
To support pharmaceutical manufacturers seeking to achieve proper control and reduce the possibility of formation of carcinogenic impurities, this application note details a sensitive, specific, precise and accurate quantitative analytical method for the analysis of NDMA impurities in ranitidine, utilizing a QSight® 120 UHPLC/MS/MS.