Journal
CLINICA CHIMICA ACTA
Volume 421, Issue -, Pages 152-156Publisher
ELSEVIER
DOI: 10.1016/j.cca.2013.02.009
Keywords
Tacrolimus; Sirolimus; Cyclosporin A; Dried blood spot assay; Immunosuppressant monitoring; Mass spectrometry
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Background: Therapeutic drug monitoring of immunosuppressive drugs is important in transplant patients. We developed and validated liquid chromatography-mass spectrometry (LC-MS/MS) assay for simultaneous quantitation of tacrolimus (TaC), sirolimus (SrL), and cyclosporin A (CsA) in dried blood spots (DBSs) to offer patients home sample collection, avoiding travel for blood draws. Methods: After extraction, samples were analyzed by LC-MS/MS in multiple reaction monitoring mode. Results: The assay was linear between 1.2-40 ng/ml for TaC and SrL, and 30-1000 ng/ml for CsA. Inter- and intra-assay CVs were <= 14.8% for all 3 drugs. This method correlated well with the existing clinical whole blood assay, with coefficients of determination >0.95 for all 3 drugs. DBS quality control samples were stable for at least 30 days at -20,4, and 25 degrees C. Stability of patient DBS samples was at least 5 days at temperatures up to 60 degrees C, except for SrL where degradation was observed at 60 degrees C within 24 h. No effect of hematocrit level, blood spot volume or punch location was observed. Conclusion: Immunosuppressant levels measured in DBS correlate with whole blood LC-MS/MS assay and may contribute to successful outcome of organ transplant and patient satisfaction. (C) 2013 Elsevier B.V. All rights reserved.
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