Determination of mycophenolic acid in human plasma by ultra-performance liquid chromatography–tandem mass spectrometry and its pharmacokinetic application in kidney transplant patients

To implement and validate an analytical method by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC MS/MS) to quantify mycophenolic acid (MPA) in kidney transplant patients. Quantification of MPA was performed in an ACQUITY UPLC H Class system coupled to a Xevo TQD detector and it was extracted from plasma samples by protein precipitation. The chromatographic separation was achieved through an ACQUITY HSS C18 SB column with 0.1%25 formic acid and acetonitrile (60:40 vol/vol) as mobile phase. The pharmacokinetic parameters were calculated by non-compartmental analysis of MPA plasma concentrations from 10 kidney transplant patients. The linear range for MPA quantification was 0.2–30 mg/L with a limit of detection of 0.07 mg/L; the mean extraction recovery was 99.99%25. The mean intra- and inter-day variability were 2.98%25 and 3.4%25 with a percentage of deviation of 8.4%25 and 6.6%25, respectively. Mean maximal concentration of 10 mg/L at 1.5 h, area under the concentration–time curve of 36.8 mg·h/L, elimination half-life of 3.9 h, clearance of 0.32 L/h/kg and volume of distribution of 1.65 L/kg were obtained from MPA pharmacokinetics profiles. A simple, fast and reliable UPLC–MS/MS method to quantify MPA in plasma was validated and has been applied for pharmacokinetic analysis in kidney transplant patients. © 2019 John Wiley %26 Sons, Ltd.

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