Work

Microdroplet Mass Spectrometry Enables Rapid and Sensitive Measurement of Glucose Homeostasis for Elucidating Mechanism of Drug Action

Year: 2025

Type: article

Abstract: Microdroplet chemistry has recently gained much attention, as reactions can be greatly accelerated in microdroplets. This study reports its first application in pharmaceutical bioanalysis settings to measure glucose homeostasis with unprecedented speed and sensitivity. Quantifying metabolic flux is critical for understanding drug action, but traditional isotope kinetic assays face challenges including the need of lengthy sample preparation and using radioactive tracers. To tackle these challenges, we used microdroplet reaction to facilitate on-the-fly derivatization in microseconds during mass spectrometry (MS) analysis, which increased sample throughput and sensitivity and avoided the use of radioactive tracers. This technique allowed us to elucidate a mechanism through which Semaglutide affects the levels of endogenous 12 C-glucose and exogenous [U– 13 C 6 ]glucose in mouse plasma and to quantify Pioglitazone-mediated changes of glucose uptake in mouse hearts. Such microdroplet-based bioanalysis would have an immediate high impact in characterizing disease phenotypes and guiding a mechanistic understanding of new drug discovery.

Source: Analytical Chemistry

DOI: 10.1021/acs.analchem.5c01759