Analysis of Cyclosporin A in Hair Samples From Liver Transplanted Patients

作者：Mueller Alexander; Jungen Hilke; Iwersen Bergmann Stefanie; Sterneck Martina; Andresen Streichert Hilke

来源：Therapeutic Drug Monitoring, 2013, 35(4): 450-458.

DOI：10.1097/FTD.0b013e31828abb1d

• cyclosporin A
• hair analysis
• liquid chromatography
• mass spectrometry

Introduction: Cyclosporin A (CsA) is one of the most important immunosuppressants currently used to prevent organ rejection after liver transplantation. Therapeutic benefit and adverse toxicity are associated with only small differences in CsA blood concentration. Correct individual dosage and compliance are therefore essential for successful therapy. To this end, we developed a validated analytical assay for the determination of CsA in hair samples. Hair samples from patients treated with CsA after liver transplantation were analyzed to investigate correlations between hair concentrations, blood concentrations, and CsA doses. The aim of this study was to evaluate whether hair analysis could be useful for the long-term follow-up of liver transplantation patients.Materials and Methods: Hair samples from patients were segmented and decontaminated. After alkaline hydrolysis and liquid-liquid extraction, CsA was analyzed by liquid chromatography-tandem mass spectrometry.Results: The peptide CsA (molecular weight 1202.6 Da) was detected in all the patient hair segments corresponding to times of CsA intake, whereas all hair segments reflecting times without CsA treatment tested negative. Correlation between CsA hair concentrations and CsA doses was poor. Consequently, it was not possible to verify the amount of CsA intake by hair analysis. A correlation coefficient of r(2) = 0.57 was found for the correlation of average whole blood trough concentrations and hair concentrations. The segmental CsA hair concentrations were found to be much steadier than the whole blood trough concentrations. In patients with stable or slightly changed CsA dosages, a comparable segmental concentration profile with a decrease in CsA hair concentrations from proximal to distal was found. Major modifications in CsA dosage are followed by a corresponding trend in segmental hair concentrations.Conclusions: Our results suggest that it is not possible to quantify the amount of CsA intake by hair analysis. Segmental hair analysis might be useful in the detection of substantial noncompliance and to detect changes in drug-taking behavior.

• 出版日期2013-8