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

Massimo Tempestilli, Enrico Di Stasio, Maria Rosaria Basile, Federica Elisei, Mario Antonini, Giuseppe Maria Ettorre, Massimo Iappelli, Leopoldo Paolo Pucillo

Research output: Contribution to journalArticle

11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)96-100
Number of pages5
JournalTherapeutic Drug Monitoring
Volume35
Issue number1
DOIs
Publication statusPublished - Feb 2013

Fingerprint

Tacrolimus
Immunoassay
Serum Albumin
Liver Transplantation
Transplants
Liver
Multivariate Analysis
Kidney
Tandem Mass Spectrometry
Liquid Chromatography
Quality Control
Immunosuppression
Demography

Keywords

  • ACMIA
  • assay interference
  • LC-MS/MS
  • tacrolimus
  • therapeutic drug monitoring

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology

Cite this

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. / Tempestilli, Massimo; Di Stasio, Enrico; Basile, Maria Rosaria; Elisei, Federica; Antonini, Mario; Ettorre, Giuseppe Maria; Iappelli, Massimo; Pucillo, Leopoldo Paolo.

In: Therapeutic Drug Monitoring, Vol. 35, No. 1, 02.2013, p. 96-100.

Research output: Contribution to journalArticle

Tempestilli, Massimo ; Di Stasio, Enrico ; Basile, Maria Rosaria ; Elisei, Federica ; Antonini, Mario ; Ettorre, Giuseppe Maria ; Iappelli, Massimo ; Pucillo, Leopoldo Paolo. / 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. In: Therapeutic Drug Monitoring. 2013 ; Vol. 35, No. 1. pp. 96-100.
@article{673846f120be42fa9de3b0a133b0a8aa,
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.",
keywords = "ACMIA, assay interference, LC-MS/MS, tacrolimus, therapeutic drug monitoring",
author = "Massimo Tempestilli and {Di Stasio}, Enrico and Basile, {Maria Rosaria} and Federica Elisei and Mario Antonini and Ettorre, {Giuseppe Maria} and Massimo Iappelli and Pucillo, {Leopoldo Paolo}",
year = "2013",
month = "2",
doi = "10.1097/FTD.0b013e318279dfd2",
language = "English",
volume = "35",
pages = "96--100",
journal = "Therapeutic Drug Monitoring",
issn = "0163-4356",
publisher = "Lippincott Williams and Wilkins",
number = "1",

}

TY - JOUR

T1 - 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

AU - Tempestilli, Massimo

AU - Di Stasio, Enrico

AU - Basile, Maria Rosaria

AU - Elisei, Federica

AU - Antonini, Mario

AU - Ettorre, Giuseppe Maria

AU - Iappelli, Massimo

AU - Pucillo, Leopoldo Paolo

PY - 2013/2

Y1 - 2013/2

N2 - 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.

AB - 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.

KW - ACMIA

KW - assay interference

KW - LC-MS/MS

KW - tacrolimus

KW - therapeutic drug monitoring

UR - http://www.scopus.com/inward/record.url?scp=84872843503&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84872843503&partnerID=8YFLogxK

U2 - 10.1097/FTD.0b013e318279dfd2

DO - 10.1097/FTD.0b013e318279dfd2

M3 - Article

C2 - 23191996

AN - SCOPUS:84872843503

VL - 35

SP - 96

EP - 100

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 1

ER -