Detection and quantification of Nitrosamines in Omeprazole, Esomeprazole and Pantoprazole

Abstract

Nitrosamines are species characterized by the chemical structure R2N-N=O. Studies on rats have highlighted their carcinogenic potential in organs such as the esophagus, oral cavity, brain, stomach and urinary bladder. To date, the International Agency for Research on Cancer (IARC) has classified dimethylnitrosamine (NDMA) and diethylnitrosamine (NDEA) as possible carcinogens for humans, and related studies on other nitrosamines are being conducted. Such species can be present in various foods and have even been found in medicines such as valsartan and ranitidine, which has led to global concerns about patients' health. Nitrosamines result from reactions in acidic environments between nitro groups and secondary amines, which may be present in nitrocellulose packaging or from biological interactions. These facts have prompted the search for methods to detect, quantify and mitigate such compounds in Active Pharmaceutical Ingredients (APIs) and medicines. The most widely used techniques for determining nitrosamines include liquid chromatography (LC) and gas chromatography (GC), both coupled to mass spectrometers (MS). Both are effective for identifying compounds in complex samples, such as drugs. Since there are no studies using these techniques to identify nitrosamines in medications such as Omeprazole, Esomeprazole and Pantoprazole, this work aims to optimize and apply methodologies based on LC-MS and GC-MS to quantify nitrosamines in the drugs mentioned.