Simple assay of plasma sevoflurane and its metabolite hexafluoroisopropanol by headspace GC–MS

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2010-01, Vol.878 (1), p.45-50
• Main Authors: Bourdeaux, Daniel, Sautou-Miranda, Valérie, Montagner, Agnès, Perbet, Sébastien, Constantin, Jean Michel, Bazin, Jean-Etienne, Chopineau, Jean
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Anesthetic conserving device; Anesthetics, Inhalation - blood; Anesthetics, Inhalation - chemistry; Anesthetics, Inhalation - pharmacokinetics; Biological and medical sciences; Drug Stability; Fundamental and applied biological sciences. Psychology; Gas Chromatography-Mass Spectrometry - methods; General pharmacology; Headspace gas chromatography; HFIP; Humans; Linear Models; Mass spectroscopy; Medical sciences; Methyl Ethers - blood; Methyl Ethers - chemistry; Methyl Ethers - pharmacokinetics; Pharmacokinetic study; Pharmacology. Drug treatments; Propanols - blood; Propanols - chemistry; Propanols - pharmacokinetics; Reproducibility of Results; Sensitivity and Specificity; Sevoflurane; Temperature
• ISSN: 1570-0232; 1873-376X
• DOI: 10.1016/j.jchromb.2009.11.018

The anesthetic sevoflurane can now be delivered over periods of up to 48 h 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 1–150 μg/ml, and presents high accuracy and precision. LOD and LOQ are 0.2 and 1 μg/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 4 μg/ml, respectively. Sevoflurane quickly tailed off after inhalation was stopped, and HFIP levels remained low.