Abstract
Irbesartan (IRB), an angiotensin II receptor AT1 blocker, is an antihypertensive agent commonly used with Sitagliptin (STG), a novel antidiabetic agent in diabetes. A finalised and validated LC-MS/MS method was used for the bioanalytical quantification of STG and IRB to be applicable to studies on the P.K drug-drug interactions between STG and IRB. Using a YMC triart C18 column (50 mm × 4.6 mm i.d., 3 µm), both the drugs and the Tolbutamide were separated using a gradient mode with a flow rate of 1 ml/min with run time of 5 min. For analyte detection, an LC-MS/MS system with multiple reaction monitoring (MRM) was used. The technique was validated across a concentration range of 5-1000 ng/ml, with the LLOQ for both analytes being 5 ng/ml. At all QC levels accuracies from spiked samples were > 83% for both drugs and internal standards. The accuracy for STG within-batch and between-batch was found within 98.4-107.2%, and for IRB was found within 92.4-102.5%. The precision for STG within batch and between batches was less than 12.3% CV, and for IRB was less than 10.2% CV at all concentration levels. The pharmacokinetic profiles of STG and IRB were successfully applied on simultaneous oral administration to rats. This method applies to pharmacokinetic multidrug interaction studies.