Pre-Analytical Stability of Mycophenolic Acid and Its Glucuronide in Saliva Samples Stored in Cotton Salivette® Devices Before Centrifugation.

Background/

Objectives

Saliva may provide a non-invasive alternative to blood sampling for therapeutic drug monitoring (TDM) of mycophenolic acid (MPA) in children. This study assessed MPA and, secondarily, mycophenolic acid glucuronide (MPAG) in non-centrifuged Salivette® devices to determine an acceptable interval between saliva collection and laboratory processing.

Methods

Phosphate-buffered saline (PBS), artificial saliva, and saliva from five healthy adult volunteers were externally spiked with MPA and MPAG at 5 and 500 ng/mL and applied to Salivette® cotton swabs. Samples were stored for 12, 24, and 48 h at 22 °C and 6 °C and analyzed by liquid chromatography-tandem mass spectrometry. Percentage deviations from nominal concentration within ±15% were considered acceptable.

Results

In PBS, both analytes met the acceptance criterion for up to 24 h under both conditions. In artificial saliva, both met the criterion for at least 24 h and, under some conditions, for 48 h. In human saliva, all volunteer-level MPA results met the criterion after 12 h at both temperatures, whereas MPAG did not consistently meet it. Mean MPA deviations across volunteers ranged from -10.8 to 1.9% at 22 °C and from -12.3 to 2.4% at 6 °C.

Conclusions

MPA met the acceptance criterion after 12-h in non-centrifuged Salivette® devices, supporting the feasibility of a 12-h pre-centrifugation interval under comparable conditions. Prompt centrifugation and processing are advisable when MPAG determination is required. Confirmation using incurred post-dose saliva from pediatric patients receiving mycophenolate mofetil is required.