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A candidate reference measurement procedure for Cyclosporine A in whole blood

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Abstract

Monitoring of Cyclosporine A (CsA) concentrations in whole blood is widely performed due to the narrow therapeutic index of the drug. Required standardisation for routine analysis of CsA is still missing. The candidate reference measurement procedure presented here is designated for the assignment of CsA values in hemolysed blood associated with expanded measurement uncertainty. Separate stock solutions for calibration and control materials were prepared by spiking hemolysed blood with CsA under gravimetric control. The essential sample pretreatment step was protein precipitation. Analysis was performed using isotope dilution LC-MS/MS with online solid phase extraction. Interference by matrix components was investigated. Using [2H4]-CsA as the internal standard, no interference from the investigated matrices were detected. Measurement repeatability using three pools of whole blood as samples revealed coefficients of variation (CV) ranging from 1.0 % to 1.6 %. Intermediate measurement precision was determined by repeated analysis of self-prepared control materials taken from different stock solutions of pooled whole blood. CVs were between 0.8 % and 2.4 %. Measurement accuracy was checked using three control materials prepared from three different stock solutions. The recoveries of the mean of mean values obtained on four measurement days ranged from 99.4 % to 101.3 %. The combined expanded uncertainty of measurement based on 5 days of measurement and was evaluated according to the GUM as U = 2.0 % (k = 2).

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Acknowledgments

This study was financially supported by Reference Institute for Bioanalytics (RfB), Foundation for Pathobiochemistry and Molecular Diagnostics, Bonn, Germany.

Conflict of interest

There is no conflict of interests regarding the publication of this article. Research funding had no influence on the study design.

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Authors and Affiliations

  1. Institute of Clinical Chemistry, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany

    Denis Grote-Koska, Stefan Czajkowski, Rainer Klauke, Eva Panten, Korbinian Brand & Gerhard Schumann

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  1. Denis Grote-Koska
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  2. Stefan Czajkowski
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  3. Rainer Klauke
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  4. Eva Panten
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  5. Korbinian Brand
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  6. Gerhard Schumann
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Correspondence to Denis Grote-Koska.

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Grote-Koska, D., Czajkowski, S., Klauke, R. et al. A candidate reference measurement procedure for Cyclosporine A in whole blood. Accred Qual Assur 19, 147–157 (2014). https://doi.org/10.1007/s00769-014-1048-5

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  • DOI: https://doi.org/10.1007/s00769-014-1048-5

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