Reframing immunosuppressant therapeutic drug monitoring: an integrated analytical framework based on microvolume whole blood.

Abstract

Therapeutic drug monitoring (TDM) is essential for optimizing immunosuppressive therapy after solid-organ transplantation, yet monitoring often lacks coherence due to use of multiple drug-specific specimen matrices, separate analytical workflows, and disparate drug concentration ranges. I propose using microvolume whole blood as a common biological matrix in an integrated analytical framework with the intent of reframing immunosuppressant TDM. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) permits multiple immunosuppressants to be quantified from a single, microvolume, whole-blood sample, enabling analysis of drugs that differ markedly in their clinically relevant concentrations. Analyte-specific ionization strategies can accommodate these differences in a single, integrated, analytical workflow, while hematocrit-based estimation of plasma-equivalent mycophenolic acid concentrations can link whole-blood measurements to established plasma-based clinical interpretation. In this framework, microsampling is not simply a means of reducing sample volume, but a method that supports whole-blood analysis based upon fingerstick collection, simplified specimen handling, and potentially even patient-centered or remote TDM. This Perspective discusses analytical and translational implications of using microvolume whole blood for immunosuppressant monitoring. It further considers the preanalytical, analytical, and clinical validation required to move from fragmented drug-specific testing to integrated TDM.

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