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Plasma concentrations of direct oral anticoagulants (DOAC) vary largely between individuals, while they correlate well with desired and adverse outcomes. Although regular concentration monitoring of DOAC is not recommended, information on DOAC exposure could be useful in situations, when multiple DOAC clearance pathways are impaired or non-adherence is suspected. Self-sampling techniques, like dried blood spots (DBS), would be particularly useful because they enable collecting information in ambulatory patients at relevant points in time of the dosing interval (e.g. trough). We developed and validated a DBS-based assay to quantify all currently marketed DOAC (apixaban, dabigatran, edoxaban, and rivaroxaban) in a single ultra-performance liquid chromatography/tandem mass spectrometry assay. It fulfilled all validation standards within a hematocrit range of 0.33-0.65 and was linear over a calibration range of 2.5 (apixaban, rivaroxaban), 4.4 (dabigatran), and 9.3 ng/mL (edoxaban) to 750 ng/mL. Only minor ion suppression (matrix effect ≤ 13 %) was present, inter- and intra-assay precision were ≤ 13 %, and inter- and intra-assay accuracies ranged between 88-110 %. All DOAC were stable in DBS up to 52 days at room temperature, if DBS were protected from light and humidity. The correlation between (whole blood) DBS and plasma concentrations was assessed in 33 patients under regular DOAC therapy. Deming regression coefficients between simultaneously collected capillary DBS and plasma samples were used to predict plasma concentrations from DBS. Bland-Altman plots revealed a strong agreement between predicted and observed plasma concentrations, thus, confirming the suitability of DBS for DOAC monitoring as an important step towards the important aim of self-sampling at home.
PMID: 29985592 [PubMed - as supplied by publisher]