Objective  To establish a liquid chromatography-tandem mass spectrometry method for determining concentration of mycophenolic acid in plasma of patients with systemic lupus erythematosus (SLE).

Methods  Multiple reaction monitoring mode, positive ion scanning and electrospray ion source were applied with ion pairs of m/ z 321.2 → 159.0 (mycophenolic acid) and m/z 327.2 → 270.0 (internal standard). 50 μL plasma sample was precipitated with acetonitrile after the addition of internal standard. The sample was separated with Welch XB-C₁₈ (50 mm×2.1 mm, 5 μm), the mobile phase consisted of 2 mmol·L^-1 ammonium acetate solution (0.1% formic acid)- acetonitrile (0.1% formic acid) with gradient elution at the flow rate of 0.8 mL·min^-1, the injection volum was 3 μL and analytical time was 3.5 min. After 20 patients with SLE were given regular oral doses of mycophenolate mofetil dispersive tablets to reach steady state, whole blood was taken and plasma was separated within 30 min before the next dose of drug, processed and analyzed.

Results  The linear range of mycophenolic acid was well accepted within 0.25-20 μg·mL−1 (r=0.997 0), the relative standard deviation of iner-and intra-day precision was 4.4%~14.7% with a accuracy of 87.5%~114.7% among each quality control level, the recovery was 93.7%-110.2%. The trough concentration of mycophenolic acid in 20 patients with SLE ranged from 285 to 5 297 ng·ml-1. After dose standardization, the trough concentrations ranged from 285.4 to 5 297 ng·ml-1·g^-1, with the coefficient of variation as high as 95.9%.

Conclusion  This is a highly specific, high-sensitive, time-saving, and simple pre-treatment method and could be finely applied to monitoring the plasma concentration of mycophenolic acid in patients with SLE.

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