Method-Comparison Validation of a Novel Capillary Blood Collection Kit, True Dose^® TD-EPI, for Therapeutic Drug...

Background: Therapeutic drug monitoring (TDM) is a promising strategy to personalize chemotherapy dosing, especially for agents with narrow therapeutic indices such as epirubicin. However, widespread adoption is hindered by logistical challenges associated with venous blood sampling and centralized laboratory workflows. Objective: This study aimed to perform a method-comparison validation of the True Dose^® TD-EPI microsampling kit by verifying analytical agreement between capillary and venous epirubicin measurements in real patient samples. The study focuses on analytical performance and does not constitute validation of the whole decentralized workflow, including unsupervised patient self-sampling. Methods: 13 patients with early-stage breast cancer receiving the first cycle of neoadjuvant or adjuvant epirubicin were enrolled. Capillary samples were collected using the finalized TD-EPI kit (Cap-TD) at 2.5 h (n = 13) and/or 48 h (n = 10) post-infusion and stored at room temperature for 72 h before analysis. Matched venous samples were analyzed using both conventional protein precipitation ("Traditional") and a modified lab-based True Dose workflow (Lab-TD). Epirubicin concentrations were quantified via validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Results: Cap-TD concentrations showed strong agreement with Traditional venous values (r = 0.953), with minimal bias (mean difference = 0.013 μM) in Bland-Altman analysis. Passing-Bablok regression confirmed analytical equivalence. Intra-assay variability remained within ICH M10 guidelines (CV ≤ 15%), and recovery was unaffected by 72 h ambient storage. Lab-TD results closely matched Traditional workflows, supporting reproducibility. Conclusions: The TD-EPI kit enables accurate decentralized monitoring of epirubicin, eliminating the need for venous access, cold-chain logistics, or in-clinic sampling. These findings support its integration into personalized oncology care and future applications in home-based TDM. Trial Registration: This study is part of an approved protocol registered in the EU Clinical Trials Register (EUCT Number 2024-514818-12-00; EudraCT Number 2017-000641-44; registration date: 15 June 2017).