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Tytuł pozycji:

Fully Automated Dried Blood Spot Extraction coupled to Liquid Chromatography-tandem Mass Spectrometry for Therapeutic Drug Monitoring of Immunosuppressants.

Tytuł:
Fully Automated Dried Blood Spot Extraction coupled to Liquid Chromatography-tandem Mass Spectrometry for Therapeutic Drug Monitoring of Immunosuppressants.
Autorzy:
Deprez S; Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium.
Stove CP; Laboratory of Toxicology, Faculty of Pharmaceutical Sciences, Ghent University, Ottergemsesteenweg 460, Ghent 9000, Belgium. Electronic address: .
Źródło:
Journal of chromatography. A [J Chromatogr A] 2021 Sep 13; Vol. 1653, pp. 462430. Date of Electronic Publication: 2021 Jul 21.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Amsterdam ; New York : Elsevier, 1993-
MeSH Terms:
Chromatography, Liquid*
Dried Blood Spot Testing*
Drug Monitoring*
Immunosuppressive Agents*
Humans ; Tandem Mass Spectrometry
Contributed Indexing:
Keywords: Automated extraction; DBS-MS 500; Dried blood spots; Immunosuppressants; Liquid chromatography-tandem mass spectrometry; Therapeutic drug monitoring
Substance Nomenclature:
0 (Immunosuppressive Agents)
Entry Date(s):
Date Created: 20210813 Date Completed: 20211018 Latest Revision: 20211018
Update Code:
20240105
DOI:
10.1016/j.chroma.2021.462430
PMID:
34384960
Czasopismo naukowe
Patients receiving immunosuppressant therapy, require intensive follow-up via therapeutic drug monitoring (TDM). This puts quite a burden on the patient involving frequent hospital visits and venipunctures and could (partially) be resolved by the use of dried blood microsamples (e.g. dried blood spots, DBS). One of the drawbacks of the use of DBS is the requirement for a dedicated, manual sample preparation. Fully automated DBS extraction systems, online coupled to standard liquid chromatography-tandem mass spectrometry (LC-MS/MS) configurations, could provide a solution for that. The aim of this study was to evaluate the use of the DBS-MS 500, online coupled to an LC-MS/MS system, for the TDM of immunosuppressants using DBS. Two methods for the quantification of tacrolimus, sirolimus, everolimus and cyclosporin A, in both DBS and whole blood, were developed and validated based on international guidelines. For the DBS method also DBS-specific parameters were taken into account. Both methods proved to be accurate and reproducible with biases below 11% (20% for the LLOQ) and CVs (%) below 14% (with a single exception) (20% for the LLOQ) over a calibration range from 1 to 50 ng/mL for tacrolimus, sirolimus and everolimus and 20 to 1500 ng/mL for cyclosporin A. Reproducible (CV < 15%) IS-compensated relative recovery values were obtained. However, a hematocrit-dependent relative recovery was observed for DBS, with lower hematocrit values yielding higher relative recoveries (and vice versa). Relative to the reference hematocrit of 0.37, this difference exceeded 15% at hematocrit extremes (0.18 and 0.60). Application on venous left-over patient samples showed reasonable agreement between the results of both methodologies (8,6,9 and 9/10 mean DBS results within 20% of the mean whole blood result for tacrolimus, sirolimus, everolimus and cyclosporin A, respectively), although also here an impact of the hematocrit could be discerned. As a next step, larger patient sets are needed to allow a better insight on how (correction for) the hct effect affects the quantification of immunosuppressants via fully automated DBS analysis.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021. Published by Elsevier B.V.)

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