RESUMO
Glimepiride (GLI) is prescribed for the management of type-2 diabetes where as pitavastatin (PIT) for the treatment of diabetes associated dyslipidemia. Both the drugs are metabolized by CYP2C9 and have the potential of altering the enzyme through either inhibition or induction. In this respect, we present a simple, fast and validated bioanalytical LC-MS/MS method for the simultaneous estimation of GLI and PIT from rat plasma. Waters XTerra RP HPLC column (4.6×100mm, 5µm) with mobile phase consisting of acetonitrile and 10mM ammonium acetate (pH-6.0) in the ratio 85:15 (v/v) at a flow rate of 1mL/min was used for the chromatographic separation. The negative ionization mode with MRM transitions: m/z 420.17â288.13 for PIT, m/z 489.59â350.12 for GLI and m/z 380.08â316.31for celecoxib as internal standard (IS). A total run time of 3min and LLOQ was found to be 5ng/mL for both PIT and GLI. The method was applied to study the drug interaction between GLI and PIT in rat liver microsomes. In vivo rat pharmacokinetics study showed there was a 1.29-fold increase in AUC0-∞ and 1.2-fold decrease in the clearance of PIT in presence of GLI. No notable difference in the pharmacokinetic profile of GLI was observed upon the intravenous co-administration of PIT.
