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

• Published in: Biomedical chromatography 2019-12, Vol.33 (12), p.e4681-n/a
• Main Authors: Reséndiz‐Galván, Juan Eduardo, Romano‐Aguilar, Melissa, Medellín‐Garibay, Susanna Edith, Milán‐Segovia, Rosa del Carmen, Chevaile‐Ramos, Alejandro, Romano‐Moreno, Silvia
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Chromatography, High Pressure Liquid - methods; Female; Humans; kidney transplant patients; Kidney Transplantation; Limit of Detection; Linear Models; Male; mycophenolic acid; Mycophenolic Acid - blood; Mycophenolic Acid - chemistry; Mycophenolic Acid - pharmacokinetics; non‐compartmental pharmacokinetics; Reproducibility of Results; Tandem Mass Spectrometry - methods; Transplant Recipients; UPLC–MS/MS; Young Adult
• ISSN: 0269-3879; 1099-0801
• DOI: 10.1002/bmc.4681

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% 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 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.