Bridging of Finger-Prick Volumetric Absorptive Microsampling and Conventional Venous Sampling with Clinical Specimens for Direct Oral Anticoagulants Analysis by LC–MS/MS

Abstract

OBJECTIVES: Direct oral anticoagulants (DOACs) are the first-line therapy for stroke prevention in non-valvular atrial fibrillation. Exposure-response analysis has shown correlations between drug concentrations and clinical outcomes, making therapeutic drug monitoring a valuable tool. Liquid chromatography–tandem mass spectrometry (LC–MS/MS) enables sensitive and accurate quantification for clinical analysis. Volumetric absorptive microsampling (VAMS) is a minimally invasive technique for collecting dried blood specimens. However, the translation from conventional venous blood sampling to VAMS and the conversion between plasma and whole-blood concentrations remain unclear. METHODS: We developed an LC–MS/MS method for quantifying four DOACs—dabigatran, apixaban, rivaroxaban, and edoxaban—in VAMS samples and applied it to paired clinical specimens to compare venous and finger-prick blood and establish conversion factors. RESULTS: Validation results support accuracy and precision of VAMS analysis by LC–MS/MS. Comparative analysis demonstrated no significant differences in concentrations between finger-prick and venous blood for dabigatran, apixaban, and rivaroxaban. Using paired clinical samples, conversion factors were derived via weighted Deming regression: 1.88, 1.57, 1.64, and 1.08 for dabigatran (n = 30), rivaroxaban (n = 33), apixaban (n = 35), and edoxaban (n = 36), respectively. The hematocrit effect was statistically significant for dabigatran. Bland–Altman analysis showed that more than 80% of samples fell within ±20% of the mean between estimated and measured plasma concentrations. CONCLUSION: These findings support the potential clinical utility of VAMS with LC–MS/MS as an accurate and convenient tool for DOAC monitoring, facilitating future implementation of precision medicine in anticoagulation management to minimize bleeding and stroke events.