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

Laboratories of
¹ Toxicology and
² Medical Biochemistry and Clinical Analysis, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
³ Department of Anesthesia, University Hospital, Ghent University, De Pintelaan 185, B-9000 Ghent, Belgium.
^a Author for correspondence. Fax 32-9-264-81-97; e-mail Andre.DeLeenheer{at}rug.ac.be.

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.

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				M.-P. L. A. Bouche, L. F. M. Versichelen, M. M. R. F. Struys, J. F. P. Van Bocxlaer, A. P. De Leenheer, E. P. Mortier, and G. Rolly No Compound A Formation with Superia(R) During Minimal-Flow Sevoflurane Anesthesia: A Comparison with Sofnolime(R) Anesth. Analg., December 1, 2002; 95(6): 1680 - 1685. [Abstract] [Full Text] [PDF]