title: Low plasma concentrations of albumin influence the affinity column-mediated immunoassay method for the measurement of tacrolimus in blood during the early period after liver transplantation.
abstract: BACKGROUND
  Monitoring of tacrolimus (TAC) concentrations in transplanted patients is necessary to ensure effective immunosuppression and to avoid adverse side effects. The fully automated analysis of TAC by the affinity column-mediated immunoassay (ACMIA), which does not require a precipitation step, may represent an efficient alternative to liquid chromatography-tandem mass spectrometry (LC-MS/MS), including in the clinically urgent situation. The aim of this work was to compare the analytical performances of ACMIA with those of LC-MS/MS and to evaluate the influence of hematological parameters, time posttransplant, and type of transplant on the results obtained from routine blood samples.
  
  
  METHODS
  Performance characteristics of ACMIA were evaluated using quality control materials and samples spiked with TAC from the International Proficiency Testing Scheme. One hundred and fifty-eight whole-blood samples from patients who received a liver (n = 55) or kidney (n = 14) transplant were assayed by ACMIA and LC-MS/MS, and hematologic, biochemical, and demographic data were collected. Univariate and multivariate statistical analyses were also performed to assess associations between the interassay differences with clinical and laboratory parameters.
  
  
  RESULTS
  For artificially spiked samples, the average difference between results obtained by ACMIA and LC-MS/MS was 0.24 ± 0.51 ng/mL (2.91 ± 7.03%). Crosschecking of calibrators and controls by both methods was in accordance with the nominal concentrations of TAC. The lower limit of quantification of ACMIA was found to be 3.0 ng/mL. The results with the 2 methods using routine samples from the transplant recipients correlated well (Spearman's r = 0.90). However, the ACMIA method demonstrated a positive mean bias of 1.78 ng/mL in comparison with LC-MS/MS. Multivariate analysis showed that liver transplant and albumin plasma concentrations significantly and independently affected ACMIA results (P = 0.033 and P = 0.001, respectively). Samples from liver transplant recipients early postsurgery were associated with a larger method bias than those from renal transplant recipients.
  
  
  CONCLUSIONS
  Results obtained by ACMIA must be interpreted cautiously, particularly at lower TAC concentrations. Patients with low plasma concentrations of albumin are likely to display higher concentrations of TAC compared with LC-MS/MS in the early postsurgery period.
authors.affiliation: Clinical Biochemistry and Pharmacology Laboratory, National Institute for Infectious Diseases L. Spallanzani IRCCS, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Tempestilli
authors.forename: Enrico
authors.initials: E
authors.lastname: Di Stasio
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Basile
authors.forename: Federica
authors.initials: F
authors.lastname: Elisei
authors.forename: Mario
authors.initials: M
authors.lastname: Antonini
authors.forename: Giuseppe Maria
authors.initials: GM
authors.lastname: Ettorre
authors.forename: Massimo
authors.initials: M
authors.lastname: Iappelli
authors.forename: Leopoldo Paolo
authors.initials: LP
authors.lastname: Pucillo
mesh_terms: D000328:Adult; D000368:Aged; D002853:Chromatography, Liquid / Q000379:methods; D016903:Drug Monitoring / Q000379:methods; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood* / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000379:methods; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012709:Serum Albumin / Q000378:metabolism*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D007166:Immunosuppressive Agents; D012709:Serum Albumin; D016559:Tacrolimus