Received on October 12, 2004
Accepted on December 21, 2004

Drug Monitoring and Toxicology

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

^* To whom correspondence should be addressed. 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 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 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.