Low level determinations of methyl methanesulfonate and ethyl methanesulfonate impurities in Lopinavir and Ritonavir Active pharmaceutical ingredients by LC/MS/MS using electrospray ionization

Methyl methanesulfonate (MMS) and ethyl methanesulfonate (EMS) have been highlighted as potential genotoxic impurities (PGIs). A sensitive LC/MS/MS method is developed and validated for the determination of MMS and EMS impurities in both Lopinavir and Ritonavir Active pharmaceutical ingredient. Method utilizes, Atlantis T3 column with electrospray ionization in multiple reactions monitoring (MRM) mode for quantitation of impurities. The proposed method is specific, linear, accurate and precise. The calibration curves show good linearity over the concentration range of 0.01-0.23 mu g/mL for MMS and 0.005-0.23 mu g/mL for EMS. The correlation coefficient obtained is >0.99 in each case. Method has very low limit of detection (LOD) and quantification (LOQ). LOD and LOQ of MMS and EMS are as low as similar to 0.002 mu g/mL and similar to 0.01 mu g/mL respectively. Method has accuracy within 80-120% for both the analytes. This method is a good quality control tool for quantitation of MMS and EMS impurities at very low levels in Lopinavir and Ritonavir. (C) 2011 Elsevier B.V. All rights reserved.