RESUMO
A sensitive and specific method using high-performance liquid chromatography (LC)-electrospray tandem mass spectrometry (ESI-MS/MS) for the determination of indapamide in human serum was developed and validated. Indapamide and an internal standard (4-diethylaminobenzoic acid) were isolated from serum samples by solid-phase extraction (SPE) with Oasis HLB 96-well plates and determined by LC-MS/MS in multiple reaction monitoring (MRM) mode. The calibration curve of serum indapamide was linear in the range of 0.2-20 ng/ml with a correlation coefficient of 0.9999. The repeatability, intermediate precisions, and accuracies at 0.2, 5, and 20 ng/ml in serum were less than 15%. The absolute recoveries of indapamide and the internal standard were 79.4-81.5% and 87.5%, respectively, and the low limit of quantitation of serum indapamide was 0.2 ng/mL. The analytical method was applied to a bioequivalence study of KYD-041 (1 mg as film-coated tablets, test formulations) and Natrix Tab.1 (1 mg as sugar-coated tablets, reference formulation). The 90% confidence interval of the ratios (test formulation/reference formulation) for log(Cmax) and log(AUCt) were in the range log(0.80)-log(1.25), which supports the conclusion that KYD-041 is bioequivalent to Natrix Tab.1 with respect to the rate and extent of indapamide absorption.
