Calibration and validation of ultraviolet time-of-flight mass spectrometry for online measurement of exhaled ciprofol

Abstract

Ciprofol (HSK 3486, C₁₄H₂₀O), a novel 2,6-disubstituted phenol derivative similar to propofol, is a new type of intravenous general anaesthetic. We found that the exhaled ciprofol concentration could be measured online by ultraviolet time-of-flight mass spectrometry (UV-TOFMS), which could be used to predict the plasma concentration and anaesthetic effects of ciprofol. In this study, we present the calibration method and validation results of UV-TOFMS for the quantification of ciprofol gas. Using a self-developed gas generator to prepare different concentrations of ciprofol calibration gas, we found a linear correlation between the concentration and intensity of ciprofol from 0 parts per trillion by level (pptv) to 485.85 pptv (R² = 0.9987). The limit of quantification was 48.59 pptv and the limit of detection was 7.83 pptv. The imprecision was 12.44% at 97.17 pptv and was 8.96% at 485.85 pptv. The carry-over duration was 120 seconds. In addition, we performed a continuous infusion of ciprofol in beagles, measured the exhaled concentration of ciprofol by UV-TOFMS, determined the plasma concentration by high-performance liquid chromatography, and monitored the anaesthetic effects as reflected by the bispectral index value. The results showed that the exhaled and plasma concentrations of ciprofol were linearly correlated. The exhaled ciprofol concentration correlated well with the anaesthetic effect. The study showed that we could use UV-TOFMS to provide a continuous measurement of gaseous ciprofol concentration at 20 second intervals.