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

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, Cexhaled exhibited a moderately strong linear correlation with Cplasma (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 (Tmax) for Cexhaled (2.00 ± 0.21 min) compared to Cplasma (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 (λz) 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.