Highly Sensitive and Selective Liquid Chromatography-Tandem Mass Spectrometry Method for the Simultaneous Determination of Upadacitinib and Atorvastatin in Rat Plasma and Its Application to a Pharmacokinetic Study.

A highly sensitive and versatile liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous quantification of upadacitinib and atorvastatin in rat plasma. The analytes and internal standard were extracted from 30 μL rat plasma using a simple protein precipitation technique. The method demonstrated excellent linearity over the concentration ranges of 0.5-500 ng/mL for upadacitinib and 0.05-100 ng/mL for atorvastatin and precision over all quality control levels. Detection was achieved using multiple reaction monitoring (MRM) in positive ionization mode. Method validation was carried out in accordance with the current ICH M10 guidance on bioanalytical method validation. The validated method was successfully applied to a pharmacokinetic study of a 10 mg oral formulation of upadacitinib and atorvastatin in rats. The pharmacokinetic results confirmed the applicability of the method for the reliable and simultaneous determination of both analytes in rat plasma.