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

Abstract

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 C 18 SB column with 0.1% 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%. The mean intra-and inter-day variability were 2.98% and 3.4% with a percentage of deviation of 8.4% and 6.6%, respectively. Mean maximal concentration of 10 mg/L at 1.5 h, area under the concentrationtime 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.

Population pharmacokinetics of mycophenolic acid in Mexican patients with lupus nephritis

“…MPA plasmatic concentrations were determined by a validated ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) technique. 17 Briefly, MPA was extracted from plasma by deproteinization with acetonitrile. Chromatographic separation was performed on an ACQUITY UPLC H Class system (Waters Corp., Milford, MA) followed by detection on a tandem quadruple mass spectrometer (XEVO TQD®; Waters Corp.).…”

Validated Simple HPLC-UV Method for Mycophenolic Acid (MPA) Monitoring in Human Plasma. Internal Standardization: Is It Necessary?

“…These methods have been compared in several reviews [ 7 , 8 , 10 , 11 ]. MS or tandem MS/MS detection was applied in a list of publications including multi-drug methods [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 ], and there are also papers with fluorescent detection [ 22 , 23 ]; however, UV spectroscopy is a most frequently used detection [ 6 , 9 , 10 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. Most methods used C8 or C18 packed columns, and detection was commonly carried out at a wavelength of ca.…”