title: Use of 19F-nuclear magnetic resonance and gas chromatography-electron capture detection in the quantitative analysis of fluorine-containing metabolites in urine of sevoflurane-anaesthetized patients.
abstract: 1: The use of fluorine-19 nuclear magnetic resonance (19F-NMR) and gas chromatography-electron capture detection (GC-ECD) in the analysis of fluorine-containing products in the urine of sevoflurane-exposed patients was explored. 2: Ten patients were anaesthetized by sevoflurane for 135-660 min at a flow rate of 6 l min(-1). Urine samples were collected before, directly after and 24 h after discontinuation of anaesthesia. 3: 19F-NMR analysis of the urines showed the presence of several fluorine-containing metabolites. The main oxidative metabolite, hexafluoroisopropanol (HFIP)-glucuronide, showed two strong quartet signals in the 19F-NMR spectrum. HFIP concentrations after beta-glucuronidase treatment were quantified by (19)F-nuclear magnetic resonance. Concentrations directly after and 24 h after discontinuation of anaesthesia were 131 +/- 41 (mean +/- SEM) and 61 +/- 19 mol mg(-1) creatinine, respectively. Urinary HFIP excretions correlated with sevoflurane exposure. 4: Longer scanning times enabled the measurement of signals from two compound A-derived metabolites, i.e. compound A mercapturic acid I (CAMA-I) and compound A mercapturic acid II (CAMA-II), as well as products from beta-lyase activation of the respective cysteine conjugates of compound A. The signals of the mercapturic acids, 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid were visible after combining and concentrating the patient urines. CAMA-I and -II excretions in patients were completed after 24 h. 5: Since 19F-nuclear magnetic resonance is not sensitive enough, urinary mercapturic acids concentrations were quantified by gas chromatography-electron capture detection. CAMA-I and -II urinary concentrations were 2.3 +/- 0.7 and 1.4 +/- 0.4 mol mg(-1) creatinine, respectively. Urinary excretion of CAMA-I showed a correlation with sevoflurane exposure, whereas CAMA-II did not. 6. The results show that 19F-nuclear magnetic resonance is a very selective and convenient technique to detect and quantify HFIP in non-concentrated human urine. 19F-nuclear magnetic resonance can also be used to monitor the oxidative biotransformation of sevoflurane in anaesthetized patients. Compound A-derived mercapturic acids and 3,3,3-trifluoro-2-(fluoromethoxy)-propanoic acid and 3,3,3-trifluorolactic acid, however, require more sensitive techniques such as gas chromatography-electron capture detection and/or gas chromatography-mass spectrometry for quantification.
authors.affiliation: Toxicology Department, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
authors.forename: H
authors.initials: H
authors.lastname: Orhan
authors.forename: J N M
authors.initials: JN
authors.lastname: Commandeur
authors.forename: G
authors.initials: G
authors.lastname: Sahin
authors.forename: U
authors.initials: U
authors.lastname: Aypar
authors.forename: A
authors.initials: A
authors.lastname: Sahin
authors.forename: N P E
authors.initials: NP
authors.lastname: Vermeulen
mesh_terms: D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000378:metabolism* / Q000652:urine; D002849:Chromatography, Gas; D017611:Fluorine Compounds / Q000652:urine*; D005462:Fluorine Radioisotopes; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008738:Methyl Ethers / Q000378:metabolism* / Q000652:urine; D012680:Sensitivity and Specificity; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D017611:Fluorine Compounds; D005462:Fluorine Radioisotopes; D008738:Methyl Ethers; D000077149:Sevoflurane