Determination of Calcineurin Inhibitors in Dried Blood Spots from Kidney Transplant Recipients

Lars Wilhelm, Martin Nitschke, Markus Meier, Reinhard Vonthein, Jan Kramer

Institute of Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany.
LADR GmbH Medizinisches Versorgungszentrum Dr. Kramer und Kollegen, Geesthacht, Germany.
LADR GmbH Medizinisches Versorgungszentrum Dr. Kramer und Kollegen, Geesthacht, Germany Medical Clinic I, Transplant Center, University Hospital of Schleswig-Holstein, Lübeck, Germany.
Medical Clinic I, Transplant Center, University Hospital of Schleswig-Holstein, Lübeck, Germany.
Medical Clinic I, Transplant Center, University Hospital of Schleswig-Holstein, Lübeck, Germany Nephrology Center Reinbek and Geesthacht, Reinbek, Germany.

DOI: 10.4236/ajac.2013.410A2004                

Abstract

Background: Determination of cyclosporine A (CsA) and tacrolimus (Tac) in dried blood spots (DBS) could enable drug monitoring in transplanted patients without the necessity of having to take venous blood samples. Therefore, we have developed a method for quantitative determination of calcineurin inhibitors (CNI) by liquid-chromatography-tandem mass spectrometry (LCMS). Methods: In a study with 68 kidney transplant recipients (KTR, 34 CsA, 34 Tac), we tested the clinical application of LCMS monitoring in DBS in comparison to LCMS in whole blood. Results: The measuring range is proven for 27.33 to 1345 ng/ml for CsA and for 1.63 to 39.7 ng/ml for Tac. The requirements for clinical chemical analyses for precision and accuracy are complied with. Stability is documented for a period of 14 days. The study showed the following deviations from LCMS in whole blood for determination of CsA and Tac in DBS after introducing a correction factor by the haematocrit (Hct) value (CsA trough level: mean = 4.7%, ±1.96 standard deviation (SD) －52.1% to 61.4%, N = 96; CsA peak level: mean = 7.3%, ±1.96 SD －39.7% to 54.4%, N = 95; Tac trough level: mean = －0.5%, ±1.96 SD －76.4% to 75.3%, N = 88; Tac peak level: mean = 3.9%, ±1.96 SD －80.1% to 88.7%, N = 92). Conclusions: Our data show comparable results with the reference method by means of LCMS in whole blood. Therefore, DBS of KTR for determination of CNI levels could be transported on filter cards by mail to the respective laboratory resistant to breakage and the hazard of infection.

Keywords

Cyclosporine A; Tacrolimus; LCMS; DBS; Immunochemistry; Kidney Transplant

Conflicts of Interest

The authors declare no conflicts of interest.

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