Therapeutic Drug Monitoring of Mycophenolic Acid

Abstract

Mycophenolic acid (MPA) is an immunosuppressant requiring therapeutic drug monitoring. Although immunoassays are commercially available, there is significant positive bias using this approach when compared to high-performance liquid chromatography or LC combined with mass spectrometry (LC/MS) or tandem mass spectrometry (LC/MS/MS). Positive bias is due to variable cross-reactivity of MPA acyl glucuronide with antibodies traditionally used in immunoassay formats. As can be expected, the magnitude of bias varies considerably. MPA strongly binds albumin and, as a result, disproportionate increases in free MPA occur in patients with uremia, hypoalbuminemia, and hepatic dysfunction. As such, monitoring free MPA poses additional challenges. Because MPA inhibits inosine monophosphate dehydrogenase, monitoring this enzyme may provide an alternative approach.

Keywords: Free fraction; Immunoassay; Liquid chromatography tandem mass spectrometry; MPA; TDM.