Determination of Nitrosamine Impurities and NDSRI in Anti-diabetic Drugs on Shimadzu LCMS-8060NX


User Benefits

- Simple and sensitive LC-MS/MS method to quantify ten nitrosamine impurities with simple sample pre-treatment - Achieve good linearity of R2> 0.999 with recovery within 70 –120 % without matrix-matched calibration


Detection of nitrosamines as impurities in drugs was first reported in June 2018 when N-nitrosodimethylamine (NDMA) was found in valsartan, an angiotensin II receptor blocker (ARB). Since then, nitrosamines have been found in other ARBs and drug classes. [1,2] Nitrosamines are a group of chemical compounds that can be found in several sources such as tobacco, cured meats, cosmetics, and pharmaceutical products. They are formed when an amine reacts with nitrite or nitrosating agents e.g., nitrous acid. Nitrosamine drug substance related impurities (NDSRIs) are a class of nitrosamine impurities that share a similar structure with the active pharmaceutical ingredients (APIs). Figure 1 shows an example of API sitagliptin and its NDSRI. Nitrosamines have been a concern due to their potential health risks, as some studies have linked them to an increased risk of cancer. As a result, regulatory authorities have implemented strict limits on the presence of nitrosamines in pharmaceutical products. It is important for pharmaceutical manufacturers to be aware of the formation and presence of nitrosamines to ensure the safety and efficacy of their products and protect patient health. The aim of this study is to present a simple and sensitive analytical method for ten nitrosamine impurities using APCI on Shimadzu LCMS-8060NX in MRM mode.