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.
AIMS: To evaluate neutralizing antibodies (NAb) against insulin icodec and explore whether an anti-drug antibody (ADA) titer threshold can guide clinically meaningful NAb testing. PATIENTS AND METHODS: A cell-based insulin icodec NAb assay was developed and applied to follow-up samples collected after 6 weeks of drug wash-out from two treat-to-target trials in insulin-naïve patients with type 2 diabetes. ADA status and titers, NAb status, efficacy, and safety outcomes were evaluated. RESULTS: Of 355 follow-up samples, 270 (76%) were ADA positive and 35 (9.9%) were NAb positive. Neither ADA nor NAb status was associated with safety or efficacy concerns. The rate of NAb positivity increased with ADA titer. A titer threshold of 200 improved reliability and interpretability and reduced the number of samples requiring NAb testing by 68%. A higher threshold would be required during active treatment because of residual drug interference. CONCLUSIONS: NAb testing. When NAb testing is required, an appropriate ADA titer threshold should guide sample selection. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov IDs NCT03751657 and NCT04795531.
The International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) convened a workshop on bioanalysis of antibody-drug conjugates (ADCs) in March 2026, in Spring House, Pennsylvania. The one-day event brought together pharmaceutical industry scientists and regulatory agency representatives to discuss bioanalytical strategies for ADC development. This report summarizes key presentations-including an industry survey on the current practices, perspectives on ADC clinical pharmacology, and regulatory considerations-along with findings from breakout sessions focused on preclinical bioanalysis, pharmacokinetic assays and modeling, and immunogenicity assessments. Workshop participants generally supported early characterization of relevant ADC-related analytes, emphasizing that analyte selection should remain risk-based and molecule-specific and that measurement strategies may be streamlined when supported by data and, when appropriate, regulatory consultation. Emerging themes included the growing use of hybrid liquid chromatography-tandem mass spectrometry (LC-MS/MS) platforms, the central role of exposure-response modeling in dose optimization and assay strategy, and risk-based approaches to immunogenicity assessment. These discussions provide a foundation for advancing ADC bioanalytical best practices and regulatory alignment in this rapidly evolving therapeutic area.
