Preanalytic Variables

Plasma or serum can be used to measure MPA and free MPA blood concentrations (187). However, plasma from EDTA-anticoagulated whole blood is the recommended specimen of choice because the same sample can be used to measure whole blood CsA, tacrolimus, and sirolimus (196). MPA and MPAG are stable in whole blood and plasma samples at room temperature for at least 4h (197). Plasma samples are stable at 4°C for 4 days and at least 11 months when stored at —20°C (196). Free MPA is stable for at least 6 months when stored at —20°C (198). Thawing and re-freezing of plasma samples can be performed up to four times without significant loss of MPA (199). When monitoring MPA during intravenous infusion of mycophenolate mofetil, whole blood samples should be immediately placed in ice and the plasma separated within 30min (200,201). This is because mycophenolate mofetil is very unstable and rapidly undergoes temperature-dependent degradation to MPA in whole blood samples placed at room temperature (200).

Trough concentrations of MPA are routinely used for drug monitoring and are generally believed to be a relatively good indicator of total drug exposure (202). This is somewhat surprising as numerous studies have shown that area under the curve (0-12 h) measurements are more predictive of total drug exposure and acute graft rejection than trough concentrations (203-205). In addition, MPA trough concentrations can vary considerably depending upon time after transplantation (205). Nevertheless, the superiority of area under the curve measurements is probably overshadowed by practical considerations such as additional testing costs and difficulties associated with the collection of multiply timed samples.

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