Clinical Sevoflurane Metabolism and Disposition

Abstract

Sevoflurane was rapidly metabolized to fluoride and HFIP, which was rapidly glucuronidated and eliminated in the urine. The overall extent of sevoflurane metabolism was approximately 5%.

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

“…Plasma concentrations of sevoflurane used as an anesthetic [6][7][8] can reach 150 g/ml for a level of sevoflurane in exhaled air of 2.5%. The sevoflurane level in exhaled air studied under sedation was 1.5%, which makes it reasonable to assume that a calibration standard can be set with an upper bound of 150 g/ml.…”

“…A new medical delivery system, the anesthetic conserving device (or AnaConDa for short), which evaporates and conserves the halogenated vapor in a respiratory filter opens up perspectives for using halogenated agents for ICU patient sedation over periods of several days [2][3][4]. The time-course patterns of the plasma concentrations of sevoflurane and its main metabolite hexafluoroisopropanol (HFIP) [5] have been determined for anesthetic sedation only over periods of a few hours [6][7][8]. The pharmacokinetic profile of sevoflurane for sedation periods up to 48 h also remains unknown.…”

Simultaneous determination of unmodified sevoflurane and of its metabolite hexafluoroisopropanol in urine by headspace sorptive extraction–thermal desorption–capillary gas chromatography–mass spectrometry

“…2). After addition of enflurane, urine samples were incubated at 100 • C for 60 min to achieve acid hydroly- sis of glucuronized HFIP [1]. No further sample preparation step was required.…”

“…It is partially excreted in urine as the unmodified halide; in addition, up to 4-6% of intake is thought to be rapidly excreted as hexafluoroisopropanol (HFIP), mostly in form of inorganic fluoride and the glucuronide complex [1,2] (Fig. 1).…”

Analyses of representative biomarkers of exposure and effect by chromatographic, mass spectrometric, and nuclear magnetic resonance techniques: Method development and application in life sciences

“…Previous attempts to measure HFIP in urine have involved extensive extraction and/or complicated derivatization steps. These include headspace gas chromatography for HFIP after hydrolysis by b-glucuronidase [88,89], or by acid [90] treatment, and direct ion-exchange chromatography for HFIP-glucuronide [91]. The present 19 F-NMR technique does not require any sample preparation except b-glucuronidase treatment.…”