Development and evaluation of a novel capillary blood collection method for decentralized therapeutic drug monitoring using the True Dose kit.

Interindividual variability in epirubicin exposure limits the efficacy of standard chemotherapy dosing based on body surface area (BSA) in breast cancer. This study evaluated a novel liquid-based capillary microsampling technology, True Dose, to enable decentralized therapeutic drug monitoring (TDM). It integrates internal standards (IS) at the blood collection point, enabling the immediate precipitation of proteins and stabilization of analytes. Analytical validation using liquid chromatography-tandem mass spectrometry (LC-MS/MS) showed that epirubicin signal responses from capillary samples corresponded with those from conventional venous samples, achieving R² values of ≥ 0.99. Intra-assay coefficient of variation (CV%) improved over time, decreasing from up to 18.6% at T0 to ≤ 11% from Day 3 onward, consistent with time-dependent matrix equilibration and improved extraction efficiency. Pre- and post-activation stability studies confirmed analyte integrity for up to 14 days at ambient temperatures. Hematocrit levels ranging from 7 to 18 g/dL showed no more than 17% signal variation, confirming matrix stability. In a clinical substudy involving 4 early-stage breast cancer patients, capillary-collected samples (n = 4 Cap-TD) yielded epirubicin/doxorubicin ratios that differed by no more than 15% from venous-derived samples; interpretation is limited by the small sample size. The findings support the feasibility of the True Dose system as a method for decentralized TDM of anthracycline (epirubicin) chemotherapy. The technology demonstrated analyte stability under room temperature storage for up to 14 days, time-dependent improvement in analytical precision, and minimal hematocrit bias, warranting further investigation in a broader clinical setting.Clinical trial identification: EudraCT 2017-000641-44 (registered 27 Feb 2017); EUCT 2024-514818-12-00 (CTIS, transitioned from EudraCT).