Trace Level Quantification of Genotoxic Impurities through Atmospheric Pressure Chemical Ionization (APCI) Coupled with Triple Quardrapole Analyzer in Combination Diabetic Drug Product

Abstract

N-Nitrosamine impurities have been found in several drug products, showing a concern for regulatory aspects. The study presents the development and validation of a sensitive LC-MS/MS method for detecting eight nitrosamines in vildagliptin and metformin drug products. The developed method was specific and linearity was ranged 3.53-55.92 ppb for NDMA, 3.18-50.37 ppb for NMBA, 0.97-15.41 ppb for NDEA, 0.98-15.52 ppb for NEIPA, 1.00-15.86 ppb for NDIPA, 0.98-15.46 ppb for NDBA, 0.98-15.58 ppb for NMPA and 0.7-15.32 ppb for NDPA with correlation coefficient (r) was more than 0.98 and square of correlation coefficient (r2) was found to be greater than 0.96. The LOQ were obtained in the range of 0.97-3.53 ppb with %RSD in the range of 2.5-10.9% for eight nitrosamines showed good sensitivity. Accuracy was found in the range of 98.63 ± 5.77-125.17 ± 3.68% at LOQ level, 74.77 ± 0.83-88.17 ± 0.15% at 50% level, 79.93 ± 8.47-89.00 ± 0.61% at 100% level and 74.67 ± 2.31-84.03 ± 0.93% at 150% level for the eight nitrosamine impurities that were well within acceptance criteria of not less than 70% and not more than 130%. The method validation results demonstrated that the method is precise, accurate and linear, can be applied to quantify the nitrosamines in vildagliptin and metformin drug products.