Objective: The main goal of this research was to develop a simple, rapid and sensitive liquid chromatography/tandem mass spectrometry (LC–MS/ MS) method for the simultaneous quantification of mycophenolate mofetil and mycophenolic acid. Methods: Sample extraction was carried out using a simple solid phase extraction (SPE) technique. The extracted samples were chromatographed on a C18 column using an isocratic mobile phase composed of acetonitrile and 0.1% formic acid buffer (80:20, v/v) pumped at a flow rate of 1.00 mL/min. Results: Method linearity was established in the concentration range of 0.10–20.0 ng/mL for mycophenolate mofetil and 101–19955 ng/mL for mycophenolic acid. Intra–day and inter–day precision and accuracy results of mycophenolate mofetil and mycophenolic acid were well within the acceptance criteria specified in the US FDA and EMEA guidelines. Conclusion: The projected LC–MS/MS assay method is simple, rapid and sensitive for the simultaneous determination of mycophenolate mofetil and mycophenolic acid in human plasma. This method was successfully used to quantitate the in–vivo plasma concentrations obtained from a pharmacokinetic study.
Key words: Mycophenolate mofetil, Mycophenolic acid, Human plasma, Liquid chromatography–tandem mass spectrometry (LC–MS/MS), Method validation, Pharmacokinetics.