An Investigation Into the Bias Between Liquid Chromatography–Tandem Mass Spectrometry and an Enzyme Multiplied Immunoassay Technique for the Measurement of Mycophenolic Acid

Autor: Paul J. Taylor, Michael E. Franklin, J. Michael Tredger, Christopher E. Gonde, Eyrun N Einarsdottir, Nigel W. Brown, Maria Pires
Rok vydání: 2010
Předmět:
Zdroj: Therapeutic Drug Monitoring. 32:420-426
ISSN: 0163-4356
DOI: 10.1097/ftd.0b013e3181e6b348
Popis: 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.
Databáze: OpenAIRE