Quantification of Mycophenolic Acid in Plasma by High Performance Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Abstract

Mycophenolate mofetil (MMF) and sodium mycophenolate are commonly prescribed immunosuppressive drugs for patients who have undergone solid organ transplant. Therapeutic drug monitoring (TDM) of these drugs is performed by assessing mycophenolic acid (MPA) in plasma. Due to the large inter-individual variability and narrow therapeutic range, the precise determination of systemic MPA concentration carries great clinical significance. We present a rapid, sensitive, specific, and robust liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitation of MPA in plasma. A Waters Xevo TQ-S Micro mass spectrometer coupled to a Water's Acquity liquid chromatography system was used in positive electrospray ionization (ESI) mode. MPA quantitation was achieved using multiple reaction monitoring (MRM). Mycophenolic acid carboxybutoxy ether (MPAC) was employed as an internal standard. The method is linear from 0.25 to 40.00 mg/L, has intra-assay (N = 24) imprecision of 2.7% at 1.57 mg/L and 3.9% at 4.61 mg/L and inter-assay (N = 20 days) imprecision of 4.0% at 1.62 mg/L and 5.6% at 4.68 mg/L.

Keywords: Liquid chromatography; Mass spectrometry; Mycophenolic acid; Plasma; Quantification.