DEVELOPMENT OF GC-MS/MS METHOD FOR SIMULTANEOUS ESTIMATION OF FOUR NITROSOAMINES GENOTOXIC IMPURITIES IN VALSARTAN
- 31 August 2022
- journal article
- research article
- Published by Galenos Yayinevi in Turkish Journal of Pharmaceutical Sciences
- Vol. 19 (4), 455-461
- https://doi.org/10.4274/tjps.galenos.2021.17702
Abstract
Objectives: Recently, N-nitrosamines were unexpectedly detected in valsartan and other generic sartan products. Taking into this account, we developed a sensitive and stable multiple reaction monitoring mode-based "gas chromatography-tandem mass spectrometry (GC-MS/MS)" approach for the quantification of "four N-nitrosamines" in valsartan, especially, N-nitrosodiisopropylamine, N-nitroso ethyl isopropylamine, N-nitrosodiethylamine, and N-nitrosodimethylamine.Materials and Methods: GC and MS conditions were optimized with specificity, sensitivity, linearity, precision, and accuracy of the parameters. The approach was validated as per the "International Council for Harmonization" recommendations.Results: The identification limits and limits of quantification of N-nitrosamines in valsartan varied between 0.02 and 0.03 ppm, and 0.06-0.09 ppm, respectively. The obtained values were satisfactory with limits established by the United States Food and Drug Administration for sensitivity requirements. The regression coefficients greater than 0.999 for four N-nitrosamines in the calibration curve demonstrated the strong linearity of the process. The retrievals of "N-nitrosamines" in valsartan between 91.9-122.7%. For the intra-day and inter-day accuracy studies, the (relative standard deviation) was less than 9.15%.Conclusion: The proposed approach has rapid analysis capability, high precision, accuracy, and good sensitivity, which give a reliable approach for N-nitrosamines quality control in valsartan.Keywords
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