Measurement of mycophenolic acid in plasma or serum by a commercial enzyme inhibition technique in comparison with a high performance liquid chromatography method.
BACKGROUND
Mycophenolic acid (MPA) is the primary active metabolite of the immunosuppressant mycophenolate mofetil. High performance liquid chromatography (HPLC) is commonly used for therapeutic drug monitoring (TDM) of MPA but requires batched runs. Recently, an enzyme inhibition assay (EIA) was approved for MPA TDM on random-access platforms using either serum or EDTA plasma. We evaluated the EIA on a Roche Integra 400 using serum and heparinized plasma in comparison with a validated HPLC method.


METHODS
Heparinized plasma from leftover clinical samples on which MPA was ordered along with paired serum samples, drawn at the same time for other clinical tests, were used for the method comparison.


RESULTS
The EIA was linear from 3.1 to 44.0 micromol/L with an accuracy of 93.9%-107.1%. The intra- and inter-day variations were 0.5%-2.7% and 1.6%-2.1%, respectively. The limit of detection was 0.8 micromol/L and the limit of quantification was 3.1 micromol/L. The method showed a mean bias of 0.6 micromol/L (7.6%) in serum samples (3.1-34.1 micromol/L) vs. the HPLC method using paired plasma (n=229). Heparinized plasma (n=114) vs. serum showed a mean bias of -0.1 mumol/L (-1.6%) by the EIA.


CONCLUSIONS
The random-access EIA on Integra 400 is acceptable for clinical MPA TDM in either serum or heparinized plasma.
Bunch
Dustin R
DR
Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, USA.
Wang
Sihe
S
D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007168:IMP Dehydrogenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009173:Mycophenolic Acid / Q000097:blood* / Q000378:metabolism; D015203:Reproducibility of Results
D006493:Heparin; D007168:IMP Dehydrogenase; C501687:IMPDH2 protein, human; D009173:Mycophenolic Acid