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 CO(2) 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 microL/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 microL/L, and the limit of quantification was 0.3 microL/L. Analytical recoveries were 100.6% +/- 10.1%, 102.5% +/- 7.3%, and 99.0% +/- 4.1% at 0.5, 10, and 75 microL/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.
Bouche
M P
MP
Laboratory of Toxicology, Ghent University, Harelbekestraat 72, B-9000 Ghent, Belgium.
Van Bocxlaer
J F
JF
Rolly
G
G
Versichelen
L F
LF
Struys
M M
MM
Mortier
E
E
De Leenheer
A P
AP
D000388:Air / Q000032:analysis; D018685:Anesthetics, Inhalation / Q000737:chemistry*; D004987:Ethers / Q000032:analysis*; D008401:Gas Chromatography-Mass Spectrometry; D006845:Hydrocarbons, Fluorinated / Q000032:analysis*; D008738:Methyl Ethers / Q000737:chemistry* / Q000633:toxicity; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077149:Sevoflurane; D014835:Volatilization
D018685:Anesthetics, Inhalation; D004987:Ethers; D006845:Hydrocarbons, Fluorinated; D008738:Methyl Ethers; D000077149:Sevoflurane; C078742:fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether