Comparison of plasma and oral fluid concentrations of mycophenolic acid and its glucuronide metabolite by LC-MS in kidney transplant patients
Mycophenolic acid is one of the most used immunosuppressive drugs in solid organ transplant treatments in the world. Developing a highly sensitive analytical method to analyse the drug and its metabolites in oral fluid and plasma is important to evaluate the possibility of using oral fluid as a biological matrix in therapeutic drug monitoring, instead of plasma.
The liquid chromatography coupled to mass spectrometry (LC-MS) method was developed and validated for determining mycophenolic acid (MPA) and its glucuronide metabolite (MPAG) in oral fluid and plasma, with both matrices presenting a detection limit of 1 ng/mL for MPA and 5 ng/mL for MPAG. Both analytes were analysed after a simple protein precipitation procedure. Transplanted-kidney samples of oral fluid and blood were collected from 13 patients that were hospitalised and kept at − 80 °C until analyses.
The proposed method was linear in the concentration range of 5–500 ng/mL for MPA and 10–500 ng/mL for MPAG, with correlation coefficients (r) between 0.9925 and 0.9973. It was then applied to samples collected from kidney-transplanted patients and used for calculation of pharmacokinetics parameters.
After comparing plasma and oral fluid concentrations as well as performing a non-compartmental pharmacokinetic analysis of the average curves, it is possible to suggest that oral fluid concentration may be used as an alternative for MPA and MPAG monitoring in kidney transplant patients.
KeywordsLC-MS Oral fluid Plasma Mycophenolic acid Mycophenolic acid glucuronide Pharmacokinetic
The authors wish to thank CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) and PPGCF-UFRGS (the Postgraduate Program in Pharmaceutical Sciences - Federal University of Rio Grande do Sul) for the financial support, and the team on the 7th floor, especially the nurses, of Hospital São Lucas da PUC for their support and availability to perform the sample collections.
Compliance with ethical standards
Conflicts of interest
The authors declare that they have no conflict of interest.
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