Inter-laboratory Variability of Current Immunoassay Methods for Tacrolimus among Japanese Hospitals

Abstract

The aim of this study was to assess inter-hospital laboratory variability (coefficient of variation; CV) of immunoassay methods for tacrolimus and the comparability of control samples and results obtained by immunoassay measurements. One hundred seven hospital laboratories routinely performing therapeutic drug monitoring (TDM) of tacrolimus participated in the study. Thirteen spiked samples with known tacrolimus concentrations in the range of 0-26.0 ng/mL were prepared. Each spiked sample was analyzed according to the manufacturer's instructions using an affinity column-mediated immunoassay (ACMIA) on a Dimension ® analyzer, the enzyme multiplied immunoassay technique (EMIT) on a Viva-E ® analyzer, a chemiluminescent enzyme immunoassay (CLIA) on the Architect ® system, and the electro-chemiluminescence immunoassay (ECLIA) on a cobas ® analyzer. The 20% coefficient of variation values for the CLIA, ACMIA, EMIT, and ECLIA assays in the hospital laboratories were 1.82, 5.36, 4.59, and 0.89 ng/mL, respectively. CLIA and ECLIA had positive biases at concentrations of tacrolimus above 12 ng/mL relative to the spiked concentration, whereas the assay bias for ACMIA tended to be more negative at concentrations of tacrolimus above 6 ng/mL. EMIT had positive biases over the wide concentration range of 0.0-26.0 ng/mL (mean of mean errors 1.224). CLIA and ECLIA provided adequate precision at the target tacrolimus concentration of 3.0 ng/ mL, whereas ACMIA and EMIT were unable to respond to target concentrations between 3.0 and 5.0 ng/ mL for renal transplant recipients. Appropriate assessment of tacrolimus concentration by an assay having higher sensitivity, precision, and accuracy is necessary to ensure long-term survival of transplant recipients receiving tacrolimus.

A comparison of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and enzyme-multiplied immunoassay technique (EMIT) for the determination of the cyclosporin A concentration in whole blood from Chinese patients

“…CLIA systematically yielded a higher CyA concentration than UPLC-TMS did (15). Compared to EMIT, CLIA and ECLIA have a higher sensitivity and a higher precision when measuring the tacrolimus concentration in blood (16). However, no study has compared EMIT and CLIA or ECLIA when measuring the CyA concentration as part of TDM, so this topic should be studied further.…”

Pharmacokinetic considerations related to therapeutic drug monitoring of tacrolimus in kidney transplant patients

“…The correlation of albumin with the interassay differences may possibly be explained by the presence of unbound Tac or metabolites with a lower affinity for albumin, still able to cross-react with the antibody [39]. Some studies found that immunoassays appear unable to analyze Tac concentrations in the lower concentration range (between 3.0 and 5.0 ng/mL) and have a higher coefficient of variation (CV) [40]. Tac concentration measurement by LC-MS methods have higher sensitivity, precision, and accuracy, while the application of LC-MS in individual centers is limited.…”

Recent advances in analytical methods for the therapeutic drug monitoring of immunosuppressive drugs

“…Schniedewind et al 77 Miura et al 84 The magnitude of the bias varied considerably. Monitoring free MPA creates additional challenges because free MPA approximated by the fraction of total MPA concentration may be misleading in many conditions such as uremia, hypoalbuminemia, and hepatic dysfunction.…”

“…Miura et al assessed the inter‐hospital laboratory variability of immunoassay methods for TAC. The results were obtained by immunoassay including an affinity column‐mediated immunoassay (ACMIA) on a Dimension analyzer, an enzyme‐multiplied immunoassay technique (EMIT) on a Viva‐E analyzer, a CLIA on the Architect system, and the ECLIA on a cobas analyzer.…”