Quantitative determination of vapor-phase compound A in sevoflurane anesthesia using gas chromatography-mass spectrometry

Abstract

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 vaporphase 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, find chromatographic separation of volatiles in an area complicated by limited availability of sample volume and low concentrations of the analyte. © 2001 American Association for Clinical Chemistry.