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This Article Full Text Full Text (PDF) Data Supplement All Versions of this Article: clinchem.2004.043950v1 51/3/586    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (12) Citing Articles via Google Scholar Google Scholar Articles by Brown, N. W. Articles by Tredger, J. M. Search for Related Content PubMed PubMed Citation Articles by Brown, N. W. Articles by Tredger, J. M. Related Collections General Clinical Chemistry Drug Monitoring and Toxicology Automation and Analytical Techniques

Low Hematocrit and Serum Albumin Concentrations Underlie the Overestimation of Tacrolimus Concentrations by Microparticle Enzyme Immunoassay versus Liquid Chromatography–Tandem Mass Spectrometry

¹ Immunosuppressive Drug Monitoring, Institute of Liver Studies, King’s College Hospital, London, UK.
² Institute of Liver Studies, Guy’s King’s and St. Thomas’ School of Medicine, King’s College London, London, UK.

^aAddress correspondence to this author at: Immunosuppressive Drug Monitoring, Institute of Liver Studies, King’s College Hospital, Denmark Hill, London SE5 9RS, UK. Fax 44-20-7346-3760; e-mail nigel.brown{at}kingsch.nhs.uk.

Background: Rapid liquid chromatography–tandem mass spectrometry (LC-MS/MS) methods are used increasingly for tacrolimus (TRL) monitoring but show a negative difference with respect to a microparticle immunoassay (MEIA). This report examines possible reasons for this difference between methods.

Methods: We collected 1156 blood samples from 277 adult and 121 pediatric recipients of liver, renal, and bone marrow grafts or hepatocyte or pancreatic islet cell implants. TRL was measured in whole blood by MEIA and LC-MS/MS, and hematologic and biochemical data were collected when available.

Results: LC-MS/MS was significantly more precise (P <0.02) than the MEIA with increased sensitivity. The MEIA had a median difference of 16.2% vs LC-MS/MS overall, and this was significantly affected by patient cohort (P <0.001). The difference was greater in adult or pediatric liver graft recipients while they were inpatients rather than outpatients (31.8% and 14.0% vs 7.5% and 6.5%, respectively). The difference was also greater in bone marrow than kidney graft recipients (32.8% vs 15.8%, respectively). Multiple linear regression analysis showed significant inverse relationships of this difference with hematocrit (packed cell volume) and plasma albumin (P <0.001) in the total cohort and a positive relationship with plasma bilirubin in a subgroup of pediatric liver graft recipients.

Conclusions: Patients with a low packed cell volume and plasma albumin are likely to show artificially high concentrations of TRL when measured by MEIA. The increased risk of underimmunosuppression must be considered should doses be reduced to lower these seemingly high TRL concentrations.

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				R. Borrows, G. Chusney, M. Loucaidou, A. James, S. Goel, S. Borrows, J. Van Tromp, T. Cairns, M. Griffith, N. Hakim, et al. Analysis of Factors Influencing Tacrolimus Levels and Immunoassay Bias in Renal Transplantation J. Clin. Pharmacol., August 1, 2007; 47(8): 1035 - 1042. [Full Text] [PDF]