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Dried blood spot analysis of creatinine with LC-MS/MS in addition to immunosuppressants analysis

Analytical and Bioanalytical Chemistry volume 407, pages 1585–1594 (2015)Cite this article

Abstract

In order to monitor creatinine levels or to adjust the dosage of renally excreted or nephrotoxic drugs, the analysis of creatinine in dried blood spots (DBS) could be a useful addition to DBS analysis. We developed a LC-MS/MS method for the analysis of creatinine in the same DBS extract that was used for the analysis of tacrolimus, sirolimus, everolimus, and cyclosporine A in transplant patients with the use of Whatman FTA DMPK-C cards. The method was validated using three different strategies: a seven-point calibration curve using the intercept of the calibration to correct for the natural presence of creatinine in reference samples, a one-point calibration curve at an extremely high concentration in order to diminish the contribution of the natural presence of creatinine, and the use of creatinine-[2H3] with an eight-point calibration curve. The validated range for creatinine was 120 to 480 μmol/L (seven-point calibration curve), 116 to 7000 μmol/L (1-point calibration curve), and 1.00 to 400.0 μmol/L for creatinine-[2H3] (eight-point calibration curve). The precision and accuracy results for all three validations showed a maximum CV of 14.0 % and a maximum bias of −5.9 %. Creatinine in DBS was found stable at ambient temperature and 32 °C for 1 week and at −20 °C for 29 weeks. Good correlations were observed between patient DBS samples and routine enzymatic plasma analysis and showed the capability of the DBS method to be used as an alternative for creatinine plasma measurement.

From blood spot to chromatogram

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The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Clinical Pharmacy and Pharmacology, Laboratory for Clinical and Forensic Toxicology and Drugs Analysis, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB, Groningen, The Netherlands

    Remco A. Koster, Ben Greijdanus, Jan-Willem C. Alffenaar & Daan J. Touw

  2. Department of Pharmacy, Section Pharmacokinetics, Toxicology and Targeting, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands

    Daan J. Touw

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  1. Remco A. Koster
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  2. Ben Greijdanus
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  3. Jan-Willem C. Alffenaar
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  4. Daan J. Touw
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Correspondence to Remco A. Koster.

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Koster, R.A., Greijdanus, B., Alffenaar, JW.C. et al. Dried blood spot analysis of creatinine with LC-MS/MS in addition to immunosuppressants analysis. Anal Bioanal Chem 407, 1585–1594 (2015). https://doi.org/10.1007/s00216-014-8415-2

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  • DOI: https://doi.org/10.1007/s00216-014-8415-2

Keywords

  • Dried blood spot
  • Creatinine
  • Tacrolimus
  • Sirolimus
  • Everolimus
  • Cyclosporin A