Development and validation of an LC-MS/MS method for the determination of pelubiprofen and its active metabolite, trans-alcohol, in human plasma and its application to pharmacokinetic study

• We have developed LC-MS/MS method to analyze pelubiprofen and its active metabolite (trans-OH) in human plasma.
• This method is selective, reproducible, and accurate.
• The validated method has been successfully applied to a pharmacokinetic study.

A suitable liquid chromatography tandem mass spectrometry (LC-MS/MS) method is required to determine pelubiprofen and its active metabolite, trans-alcohol (M-D), in human plasma for pharmacokinetic studies of pelubiprofen preparations. After one-step liquid–liquid extraction (LLE) using methyl tert-butyl ether (MTBE), pelubiprofen, M-D, and tolbutamide (the internal standard, IS) were eluted from a Capcellpak C18 ACR column using a gradient mobile phase consisting of 0.1% formic acid in water and acetonitrile at a flow rate 0.35 mL/min. The achieved lower limits of quantitation (LLOQ) of pelubiprofen and M-D were both 15 ng/mL (S/N > 10) and the standard calibration curves for pelubiprofen and M-D were linear (correlation coefficients >0.99) over the studied concentration range (15–2000 ng/mL). Intra- and inter-day precisions were within 7.62% for all analytes and the deviation of assay accuracies was within ±13.23%. The developed method was successfully applied to a pharmacokinetic study of pelubiprofen in healthy Korean male volunteers.