Simultaneous determination of sulindac and its metabolites sulindac sulfide and sulindac sulfone in human plasma by a sensitive UPLC-PDA method for a pharmacokinetic study

Abstract

A sensitive, rapid and reliable ultra-performance liquid chromatography (UPLC) with Photo-Diode Array (PDA) detection method was developed for simultaneous determination of sulindac and its metabolites sulindac sulfide and sulindac sulfone in human plasma. The analytes were extracted by dichloromethane from human plasma using a liquid–liquid extraction method. The chromatographic separation was performed on a Waters Acquity UPLC with a Waters Acquity UPLC BEH C₁₈ column (2.1 × 50 mm i.d., 1.7 μm) within 5 minutes. The mobile phase used for gradient elution consisted of ammonium formate buffer (20 mM) containing 1% acetic acid and acetonitrile. The flow rate was maintained at 0.4 mL min⁻¹. The monitor wavelength was set at 328 nm for PDA detection. All calibration curves of the analytes showed good linearity within the test ranges. The validated method was successfully applied to a pharmacokinetic study of sulindac, sulindac sulfide and sulindac sulfone in 15 healthy Chinese male subjects with oral administration of sulindac tablets.