Quantitative Determination of Vapor-Phase Compound A in Sevoflurane Anesthesia Using Gas Chromatography–Mass Spectrometry

Background: During low-flow or closed-circuit anesthesia with the fluorinated inhalation anesthetic sevoflurane, compound A, an olefinic degradation product with known nephrotoxicity in rats, is generated on contact with alkaline CO2 adsorbents. To evaluate compound A formation and thus potential sevoflurane toxicity, a reliable and reproducible assay for quantitative vapor-phase compound A determination was developed. Methods: Compound A concentrations were measured by fully automated capillary gas chromatography–mass spectrometry with cryofocusing. Calibrators of compound A in the vapor phase were prepared from liquid volumetric dilutions of stock solutions of compound A and sevoflurane in ethyl acetate. 1,1,1-Trifluoro-2-iodoethane was chosen as an internal standard. The resulting quantitative method was fully validated. Results: A linear response over a clinically useful concentration interval (0.3–75 μL/L) was obtained. Specificity, sensitivity, and accuracy conformed with current analytical requirements. The CVs were 4.1–10%, the limit of detection was 0.1 μL/L, and the limit of quantification was 0.3 μL/L. Analytical recoveries were 100.6% ± 10.1%, 102.5% ± 7.3%, and 99.0% ± 4.1% at 0.5, 10, and 75 μL/L, respectively. The method described was used to determine compound A concentrations during simulated closed-circuit conditions. Some of the resulting data are included, illustrating the practical applicability of the proposed analytical approach. Conclusions: A simple, fully automated, and reliable quantitative analytical method for determination of compound A in air was developed. A solution was established for sampling, calibration, and chromatographic separation of volatiles in an area complicated by limited availability of sample volume and low concentrations of the analyte.