Simple assay of plasma sevoflurane and its metabolite hexafluoroisopropanol by headspace GC-MS.
The anesthetic sevoflurane can now be delivered over periods of up to 48h using a newly developed medical system, the AnaConDa (anesthetic conserving device). Lack of pharmacokinetic data on sevoflurane and its main metabolite (hexafluoroisopropanol, HFIP) in this indication prompted us to develop a headspace GC-MS method to quantify the two substances. The only previously published method for assaying the two substances could not be adapted to our study since it uses expensive and rarely employed system components together with toxic carbon disulfide as a dilution solvent. The method developed is straightforward and uses the relatively non-toxic solvent undecane as dilution solvent and chloroform as internal standard. The method is linear for a concentration range of 1-150microg/ml, and presents high accuracy and precision. LOD and LOQ are 0.2 and 1microg/ml, with a short analysis time (7.6 min for a single analysis). The method was applied to determine the plasma levels of sevoflurane and HFIP in six patients under 48-h anesthetic sedation delivered via the AnaConDa system. Average sevoflurane and HFIP concentrations plateaued at 75 and 4microg/ml, respectively. Sevoflurane quickly tailed off after inhalation was stopped, and HFIP levels remained low.
Bourdeaux
Daniel
D
CHU Clermont-Ferrand, Department of Pharmacy, Hôp G Montpied, F-63003 Clermont-Ferrand, France. dbourdeaux@chu-clermontferrand.fr
Sautou-Miranda
Valérie
V
Montagner
Agnès
A
Perbet
Sébastien
S
Constantin
Jean Michel
JM
Bazin
Jean-Etienne
JE
Chopineau
Jean
J
D018685:Anesthetics, Inhalation / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D016014:Linear Models; D008738:Methyl Ethers / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D020005:Propanols / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D000077149:Sevoflurane; D013696:Temperature; D006845:Hydrocarbons, Fluorinated
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D020005:Propanols; D000077149:Sevoflurane; C001337:hexafluoroisopropanol; D006845:Hydrocarbons, Fluorinated