Development and validation of an LC-MS/MS method for simultaneous determination of three organic azido impurities in tetrazole-containing sartans

Abstract

This study aimed to develop a sensitive and simple liquid chromatography-tandem mass spectrometry for the simultaneous determination of organic azido impurities (AZBC, AZBT, and AZTT) in sartan active pharmaceutical ingredients and drug products. The method employed a HALO C8 column for chromatographic separation using gradient elution, with a mobile phase composed of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. Quantification of analytes was achieved using a triple quadrupole mass spectrometer, operating in multiple reaction monitoring mode with positive electrospray ionization. The method was fully validated following the ICH Q2 (R1) guideline, and the validation parameters met the criteria for specificity, carryover, and robustness. The developed method was found to be sufficiently sensitive, with LOD and LOQ below the acceptable limits of azido impurities in pharmaceuticals as per the ICH M7 guideline. The assay had dynamic ranges of 1.00–20.00 ng/mg for AZBC and 0.10–15.00 ng/mg for AZBT and AZTT in sartans. In conclusion, the established method was effectively utilized for determining azido impurities in sartan active pharmaceutical ingredients and drug products, achieving high accuracy and precision.