Development and application of GC-MS/MS method for determination of four Nitrosamine impurities in two Sartan drug products as per Procedure 4, USP General Chapter

Abstract

This study demonstrates that the chromatographic, mass spectrometric, and sample preparation conditions outlined in Procedure 4, USP General Chapter <1469> are compatible with the available laboratory equipment at the National Institute of Drug Quality Control for the analysis of four nitrosamine impurities: NDMA, NDEA, NEIPA, and NDIPA. We also validated the method on two finished pharmaceutical product matrices: film-coated tablets containing Losartan potassium and tablets containing Telmisartan. The results showed that the validation criteria met the requirements for both sample matrices. The method validation achieved limits of quantification (LOQ) of 0.01 to 0.03 µg/g, linearity ranges from 0.5 - 15.0 ng/mL or 5 - 100/200 ng/mL, recovery of 99.3% and 114.5%, and precision with relative standard deviations (RSDs) of 2.5% to 12.8%, indicating suitability for determining four impurities in the two studied finished products. Throughout the experiments, it was observed that the sample matrix significantly affects the nitrosamine impurity analysis. The method was then applied to analyze the four nitrosamine impurities in 13 finished product samples containing Losartan potassium and Telmisartan available on the market.