Development and application of a thin-film molecularly imprinted polymer for the measurement of mycophenolic acid in human plasma

BackgroundMycophenolic acid (MPA) is used to suppress the immune response following organ transplantation; however, complex pharmacokinetic behavior and a large interpersonal variability necessitate therapeutic drug monitoring. To overcome the limitations of current sample preparation techniques, we present a novel thin-film molecularly imprinted polymer (TF-MIP) extraction device as part of a simple, sensitive, and fast method for analysis of MPA from human plasma. MethodsMycophenolic acid is extracted from plasma using a tailor-made TF-MIP that is subsequently desorbed into an organic solvent system compatible with mass spectrometry. The MIP yielded higher recovery of MPA relative to a corresponding non-imprinted polymer. The method allows for the determination of MPA in 45 min including analysis time and can be scaled for high throughput to process as many as 96 samples per hour. ResultsThe method gave an LOD of 0.3 ng mL(-1) and was linear from 5 to 250 ng mL(-1). Patient plasma samples (35 mu L) were diluted using charcoal-stripped pooled plasma to a final extraction volume of 700 mu L; when MPA in patient plasma is high, this ratio can easily be adjusted to ensure samples are within the method linear range. Intra- and inter-day variability were 13.8% and 4.3% (at 15 ng mL(-1)) and 13.5% and 11.0% (at 85 ng mL(-1)), respectively (n = 3); inter-device variability was 9.6% (n = 10). ConclusionsLow inter-device variability makes these devices suitable for single use in a clinical setting, and the fast and robust method is suitable for therapeutic drug monitoring, where throughput and time-to-result are critical.