Quantitation of mycophenolic acid and metabolites by UPLC-MS/MS in renal transplant patients

Abstract

Mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), specific inhibitors of lymphocyte proliferation, are commonly used as adjuvant therapy with calcineurin inhibitor agents after kidney transplantation. After administration, MMF and EC-MPS are hydrolyzed to mycophenolic acid (MPA), the active form of the drug, which must be monitored due to its narrow therapeutic window, drug–drug interactions, and large intra-and inter-individual pharmacokinetic variability despite a fixed dose. Monitoring plasma MPA level is recommended to maintain the drug within the therapeutic window, optimize its efficacy, and minimize side effects. This study aims to develop a method for quantifying MPA and its major metabolites (mycophenolic acid glucuronide [MPAG]) using on-line solid phase extraction (SPE) coupled with an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in kidney transplant patients. The linearity of MPA and MPAG were 0.3–13.6 μg/mL and 2.6–232.9 μg/mL, respectively (r 2 > 0.999). The relative error of accuracy was <15%. The within-run and between-run imprecision was <5.8%. No carryover, ion suppression, or ion enhancement were observed. This method was used to analysis of 351 plasma samples from renal transplant patients after MMF or EC-MPS using this method showed large pharmacokinetic variability between patients. Analysis of the same samples by immunoassay showed a large positive bias compared with our validated UPLC-MS/MS method, averaging 15.1%. These results suggest that this UPLC-MS/MS method is more effective than immunoassay for quantitation of MPA and its metabolites in clinical samples.

Ultrathin Cu–TCPP Nanosheet-Based Electrochemical Microsensor for Detecting the Immunosuppressive Drug Mycophenolic Acid

“…These powerful properties of MPA have been exploited in solid organ transplantation to reduce the rate of rejection after transplantation. However, because of the narrow therapeutic window of MPA and notable differences between and within individuals, it is necessary to ensure individualized medication and promote the rational use of medicine. , Therefore, the quantitative analysis of MPA in patients is essential and helpful for prescribing optimal individualized medicine management and also could increase patient survival rates.…”