Capillary blood microsampling and LC-Orbitrap analysis for adherence monitoring of cardiovascular drugs: method development, cross-validation, and patient proof-of-concept using VAMS and Capitainer-B

Abstract

Microsampling enables decentralized adherence monitoring by capturing defined volumes of capillary blood. We developed, validated, and cross-evaluated a volumetric absorptive microsampling (VAMS) and Capitainer-B workflow for 15 cardiovascular drugs using high-resolution liquid chromatography Orbitrap analysis. Amlodi pine, atenolol, atorvastatin, bisoprolol, carvedilol, clopidogrel, diltiazem, lercanidipine, metoprolol, nebivolol, prasugrel, rosuvastatin, salicylic acid, simvastatin hydroxy acid, and verapamil were included. Sampling by VAMS and Capitainer-B should be evaluated and compared. VAMS tips and Capitainer-B disks loaded with 10 whole blood were extracted with 200 μ μ L L methanol, shaken and centrifuged, evaporated to dryness, reconstituted, and injected for analysis. The method met international validation criteria for most analytes, with quantification and selectivity achieved for all except prasugrel. Capitainer-B generally exhibited higher matrix effects than VAMS, while accuracy and precision were within acceptance limits except for lercanidipine across both devices and for atorvastatin on Capitainer-B. Under long-term storage, VAMS showed >15 % loss for carvedilol, lerca nidipine, and simvastatin hydroxy acid after two weeks, whereas Capitainer-B showed no degradation. In a proof-of-concept involving 30 patients, finger-prick concentrations from VAMS and Capitainer-B were inter changeable, supporting the suitability of these adherence workflows but reference ranges for capillary blood remain necessary to enable routine clinical interpretation. In summary, this work established a reliable, LC- Orbitrap-based microsampling platform for monitoring adherence and identified stability issued amongst others that guide future method selection and development.