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

Kidney transplantation is the gold standard in treatment of patients with terminal kidney failure. To prevent rejection of an allogenic donor organ, it is necessary to suppress the patient’s immune system. The cyclical peptide cyclosporine A (CsA) has been used as an immunosuppressive drug and the macrolide lactone tacrolimus (Tac) has been used in transplantation medicine.

For 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, the authors developed a method for quantitative determination of calcineurin inhibitors (CNI) by liquid-chromatography-tandem mass spectrometry (LCMS). And in a study with 68 kidney transplant recipients (KTR, 34 CsA, 34 Tac), the authors tested the clinical application of LCMS monitoring in DBS in comparison to LCMS in whole blood.

The results showed that the measuring range was 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 were complied with. Stability was 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).

In conclusion, the obtained data showed 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.

Article by Lars Wilhelm, et al, from Germany.

Full access: http://mrw.so/1VvQUH
Image by melissa.a.metz, from Flickr-cc.

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