PMID: 8585114Oct 1, 1995Paper

Simplified high-performance liquid chromatography-mass spectrometry assay for measurement of tacrolimus and its metabolites and cross-validation with microparticle enzyme immunoassay

Therapeutic Drug Monitoring
A K GonschiorK F Sewing

Abstract

In this study, a modified, specific assay for measurement of tacrolimus and its metabolites in blood and urine from transplant patients using high-performance liquid chromatography (HPLC) linked to mass spectrometry (MS) is described. Samples were prepared for HPLC-MS by modified solid-liquid extraction. The original two-step washing procedure was replaced by a single washing step, and samples were eluted with acetonitrile/water instead of dichloromethane, thus avoiding an evaporation step. Samples were injected automatically every 3 min into the HPLC-MS system. Time-consuming gradient elution was replaced by isocratic elution. This procedure resulted in a lower limit of quantitation of 0.2 microgram/L. The interassay variability was 14.5% for 5 micrograms/L and 15.8% for 25 micrograms/L. The intrassay variability was 11.2% for 5 micrograms/L and 4% for 25 micrograms/L. The recovery for tacrolimus in blood was 90.4% for 1 microgram/L, 78.9% for 10 micrograms/L, and 81.3% for 25 micrograms/L. Measurement of tacrolimus and its metabolites in samples from various transplant patients showed that the main metabolites found in blood and urine are demethyl-tacrolimus, di-demethyl-tacrolimus and demethyl-hydroxy-tacrolimus. Cross valid...Continue Reading

Citations

May 15, 2002·Clinical Chemistry and Laboratory Medicine : CCLM·Michael DetersVolkhard Kaever
Dec 4, 2004·Clinical Chemistry and Laboratory Medicine : CCLM·Pierre E Wallemacq
May 23, 2001·Clinical Pharmacokinetics·P E Wallemacq, R K Verbeeck
Jul 15, 2006·Rapid Communications in Mass Spectrometry : RCM·Simone CristoniMarco Cantu
Oct 7, 2004·Analytical Biochemistry·Yoshihiro MurakamiEiichi Tamiya
Dec 2, 2005·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Yu-Luan ChenMasakazu Kobayashi
Jul 1, 1997·Clinical Pharmacology and Therapeutics·L C FlorenM F Hebert
Apr 29, 1998·Therapeutic Drug Monitoring·P J TaylorA G Johnson
Jan 8, 1998·Therapeutic Drug Monitoring·F BraunB Ringe
Mar 13, 2012·Therapeutic Drug Monitoring·Ilse R DubbelboerOlof Beck
Nov 25, 2000·Journal of Chromatography. B, Biomedical Sciences and Applications·U ChristiansG I Kirchner
Mar 3, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·G I KirchnerK F Sewing

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