DETERMINATION OF ANTIPSYCHOTIC MEDICATIONS IN HUMAN PLASMA BY UPLC: PHARMACOKINETIC STUDY

Abstract A simple and sensitive ultra-performance liquid chromatography (UPLC) method has been developed and validated for simultaneous estimation of olanzapine (OLZ), risperidone (RIS) and 9-hydroxyrisperidone (9-OHRIS) in human plasma in vitro. The sample preparation was performed by simple liquid–liquid extraction technique. The analytes were chromatographed on a Waters Acquity H class UPLC system using isocratic mobile phase conditions at a flow rate of 0.3mL/min and Acquity UPLC BEH shield RP18 column maintained at 40°C. Quantification was performed on a photodiode array detector set at 277 nm and clozapine was used as internal standard (IS). OLZ, RIS, 9-OHRIS and IS retention times were found to be 0.9, 1.4, .1.8 and 3.1 min, respectively, and the total run timewas4min.Themethodwasvalidatedforselectivity,specificity,recovery,linearity, accuracy, precision and sample stability. The calibration curve was linear over the concentration range 1–100ng/mL for OLZ, RIS and 9-OHRIS.Intra-andinter-dayprecisionsforOLZ, RIS and 9-OHRIS were found to be good with the coefficient of variation <6.96%, and the accuracy ranging from 97.55 to 105.41%, inhuman plasma. The validated UPLC method was successfully applied to the pharmacokinetic study of RIS and 9-OHRIS in human plasma. Keywords: UPLC; risperidone; 9-hydroxyrisperidone; olanzapine; pharmacokinetics