Expeditious quantification of plasma tacrolimus with liquid chromatography tandem mass spectrometry in solid organ transplantation

Tanja R. Zijp, Tim J. Knobbe, Kai van Hateren, Jan Roggeveld, Hans Blokzijl, C. Tji Gan, Stephan J.L. Bakker, Erwin M. Jongedijk, Transplant Lines Investigators, Daan J. Touw*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Traditionally, tacrolimus is assessed in whole blood samples, but this is suboptimal from the perspective that erythrocyte-bound tacrolimus is not a good representative of the active fraction. In this work, a straightforward and rapid method was developed for determination of plasma tacrolimus in solid organ transplant recipients, using liquid chromatography tandem mass spectrometry (LC-MS/MS) with heated electrospray ionisation. Sample preparation was performed through protein precipitation of 200 µl plasma with 500 µl stable isotopically labelled tacrolimus I.S. in methanol, where 20 µl was injected on the LC-MS/MS system. Separation was done using a chromatographic gradient on a C18 column (50 × 2.1 mm, 2.6 µm). The method was linear in the concentration range 0.05–5.00 µg/L, with within-run and between-run precision in the range 2–6 % and a run time of 1.5 min. Furthermore, the method was validated for selectivity, sensitivity, carry-over, accuracy and precision, process efficiency, recovery, matrix effect, and stability following EMA and FDA guidelines. Clinical validation was performed in 2333 samples from 1325 solid organ transplant recipients using tacrolimus (liver n = 312, kidney n = 1714, and lung n = 307), which had median plasma tacrolimus trough concentrations of 0.10 µg/L, 0.15 µg/L and 0.23 µg/L, respectively. This method is suitable for measurement of tacrolimus in plasma and will facilitate ongoing observational and prospective studies on the relationship of plasma tacrolimus concentrations with clinical outcomes.

Original languageEnglish
Article number123709
Number of pages8
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1222
DOIs
Publication statusPublished - 1-Apr-2023

Keywords

  • Alternative matrices
  • Bioanalysis
  • LC-MS/MS
  • Tacrolimus
  • Transplant

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