Development and validation of a novel UV-TOF MS method for real-time exhaled propofol analysis in Beagles†

Abstract

Propofol, a fast-acting anesthetic, requires precise titration to minimize adverse effects. While plasma-based monitoring is slow, exhaled propofol offers a real-time, non-invasive alternative, though its clinical application remains limited. This study evaluates ultraviolet time-of-flight mass spectrometry (UV-TOF MS) for real-time monitoring, presenting its calibration and validation in Beagle dogs. Calibration showed excellent linearity (R² = 0.9939) over 3.23–46.13 ppbv. The intra-day imprecision at propofol concentrations of 4.61 and 23.06 ppbv was below 5.83% and 7.75%, respectively, while the inter-day imprecision was 9.69% and 9.75%, respectively. Carry-over effects were minimal, with signal recovery within 40–60 s, measuring 8.7%, 9.1%, and 4.7% at 4.61, 9.30, and 23.06 ppbv, respectively. In Beagle dogs, C_exhaled exhibited a moderately strong linear correlation with C_plasma (R² = 0.7950) and a moderate correlation with sedative effects, as indicated by the bispectral index (R² = 0.5501) after a single bolus injection. Pharmacokinetic (PK) analysis revealed a delay in peak concentration (T_max) for C_exhaled (2.00 ± 0.21 min) compared to C_plasma (1.00 ± 0.00 min). While AUC values were not directly comparable, both exhibited R_AUC > 80%, indicating reliable drug kinetic reflection. Mean residence time (MRT) and elimination rate constants (λ_z) showed no significant differences. These results suggest that exhaled breath analysis provides pharmacokinetic insights comparable to plasma, with a slight delay in peak concentration. UV-TOF MS proved to be an efficient method for detecting exhaled propofol, offering potential for real-time anesthesia monitoring in clinical settings.