title: An investigation into the bias between liquid chromatography-tandem mass spectrometry and an enzyme multiplied immunoassay technique for the measurement of mycophenolic acid.
abstract: Mycophenolic acid is now the second most widely used immunosuppressant in solid organ transplantation. Overestimation of mycophenolic acid concentration is a recognized problem of immunoassay, and high-performance liquid chromatography with ultraviolet detection methods have long analysis times and a risk of analyte coelution which may compromise high sample throughput in a clinically meaningful time frame. A novel liquid chromatography-tandem mass spectrometry assay for mycophenolic acid was developed using very small (10 microL) sample volumes and evaluated in comparison with an established immunological assay. The enzyme mediated immunoassay showed a median positive bias compared with liquid chromatography-tandem mass spectrometry of 14.6%. Linear regression analysis showed a significant positive impact of bilirubin (r2 = 0.230) on bias with further increases of r2 to 0.261, 0.286, and 0.294 with the stepwise addition of creatinine, hematocrit, and gamma-glutamyl transpeptidase, respectively. The impact of comedication and transplant type depended on the patient population: analysis of all samples showed opposing effects to analysis of those samples lacking data with biochemical variables above. The liquid chromatography-tandem mass spectrometry method described in this report is capable of measuring mycophenolic acid concentrations in very small sample volumes and in a timely fashion without the significant overestimates characterizing enzyme mediated immunoassay measurements in patients with serologic features characterizing liver or renal graft rejection.
authors.affiliation: Immunosuppressive Drug Monitoring, Institute of Liver Studies, King's College Hospital and King's College London School of Medicine, London, UK.
authors.forename: Nigel W
authors.initials: NW
authors.lastname: Brown
authors.forename: Michael E
authors.initials: ME
authors.lastname: Franklin
authors.forename: Eyrun N
authors.initials: EN
authors.lastname: Einarsdottir
authors.forename: Christopher E
authors.initials: CE
authors.lastname: Gonde
authors.forename: Maria
authors.initials: M
authors.lastname: Pires
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Taylor
authors.forename: J Michael
authors.initials: JM
authors.lastname: Tredger
mesh_terms: D000328:Adult; D015982:Bias; D002851:Chromatography, High Pressure Liquid / Q000706:statistics & numerical data*; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods / Q000592:standards; D017248:Enzyme Multiplied Immunoassay Technique / Q000706:statistics & numerical data*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood*; D007677:Kidney Function Tests; D016014:Linear Models; D008297:Male; D009173:Mycophenolic Acid / Q000097:blood*; D011153:Population; D011786:Quality Control; D053719:Tandem Mass Spectrometry / Q000706:statistics & numerical data*
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid