A volumetric absorptive microsampling LC-MS/MS method for five immunosuppressants and their hematocrit effects

Remco A Koster, Pascal Niemeijer, Herman Veenhof, Kai van Hateren, Jan-Willem C Alffenaar, Daan J Touw

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Scopus)

Abstract

AIM: The aim of this study was to develop and validate a LC-MS/MS assay for tacrolimus, sirolimus, everolimus, cyclosporin A and mycophenolic acid using volumetric absorptive microsampling tips as a sampling device and to investigate the effect on the recoveries of the analyte concentration in combination with the hematocrit (HT), which included temsirolimus (a structural analog).

RESULTS: The maximum observed overall bias was 9.6% for the sirolimus LLOQ, while the maximum overall coefficient of variation was 8.3% for the everolimus LLOQ. All five immunosuppressants demonstrated to be stable in the volumetic absorbtive microsampling tips for at least 14 days at 25°C. Biases caused by HT effects were within 15% for all immunosuppressants between HT levels of 0.20 and 0.60 l/l, except for cyclosporin A, which was valid between 0.27 and 0.60 l/l. Reduced recoveries were observed at high analyte concentrations in combination with low HT values for sirolimus, everolimus and temsirolimus.

CONCLUSION: A robust extraction and analysis method in volumetric absorptive microsampling tips was developed and fully validated. HT- and concentration-related recovery effects were observed but were within requirements of the purpose of the analytical method.

Original languageEnglish
Pages (from-to)495-508
Number of pages14
JournalBioanalysis
Volume11
Issue number6
Early online date20-Mar-2019
DOIs
Publication statusPublished - 2019

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