title: Gas chromatographic determination of ethyl glucuronide in hair: comparison between tandem mass spectrometry and single quadrupole mass spectrometry.
abstract: Ethyl glucuronide (EtG), a minor metabolite of ethanol, accumulates in hair and is currently used as a long-term marker for the detection of chronic and excessive alcohol consumption. Sensitive methods are required to differentiate teetotalers from moderate drinkers according to the established cut-off (i.e., 7 pg/mg hair). The aim of this study was to develop a sensitive method using gas chromatography coupled to tandem mass spectrometry (GC-MS/MS) operated in the negative ion chemical ionization (NICI) mode. The validated method was applied to hair samples from teetotalers, moderate and excessive alcohol consumers, and results were compared to a previously validated GC-NICI-MS method. The developed GC-NICI-MS/MS method showed linearity over a range from 2 to 400 pg/mg hair, with a limit of detection (LOD) of 0.05 pg/mg hair and a lower limit of quantification (LLOQ) of 0.2 pg/mg hair, compared to an LOD of 0.5 pg/mg hair and LLOQ of 1.5 pg/mg hair obtained with GC-NICI-MS. Furthermore, lower background noise was observed using GC-NICI-MS/MS. Comparison of results of hair samples (n=58) obtained by GC-NICI-MS and GC-NICI-MS/MS showed no significant difference between both methods (paired-sample t-test, p>0.05; mean CV=1.0%). The differences between both methods were larger for EtG concentrations<30 mg/pg hair (mean CV=1.7%) than for EtG concentrations>30 mg/pg hair (mean CV=0.7%). This suggests a higher selectivity of GC-NICI-MS/MS at lower concentrations. In conclusion, by using GC-NICI-MS/MS, a higher analytical selectivity and an improved signal to noise ratio, can be achieved. Although GC-NICI-MS would not change the interpretation of the EtG concentrations, the present GC-NICI-MS/MS method should preferentially be used for the determination of EtG in hair, especially when differentiating between teetotalers and moderate drinkers according to the current cut-off (i.e., 7 pg/mg hair).
authors.affiliation: Toxicological University of Antwerp, Universiteitsplein 1, B2610 Antwerp, Belgium. Electronic address: delphine.cappelle@uantwerpen.be.
authors.forename: Delphine
authors.initials: D
authors.lastname: Cappelle
authors.affiliation: Toxicological University of Antwerp, Universiteitsplein 1, B2610 Antwerp, Belgium; Toxicology Laboratory, ZNA Stuivenberg Hospital, Lange Beeldekenstraat 267, B2060 Antwerp, Belgium.
authors.forename: Hugo
authors.initials: H
authors.lastname: Neels
authors.affiliation: Laboratoire National de Santé, Service de Toxicologie, 1, Louis Rech, L3555 Dudelange, Luxembourg.
authors.forename: Michel
authors.initials: M
authors.lastname: Yegles
authors.affiliation: Laboratoire National de Santé, Service de Toxicologie, 1, Louis Rech, L3555 Dudelange, Luxembourg.
authors.forename: Jeff
authors.initials: J
authors.lastname: Paulus
authors.affiliation: Toxicological University of Antwerp, Universiteitsplein 1, B2610 Antwerp, Belgium.
authors.forename: Alexander L N
authors.initials: AL
authors.lastname: van Nuijs
authors.affiliation: Toxicological University of Antwerp, Universiteitsplein 1, B2610 Antwerp, Belgium.
authors.forename: Adrian
authors.initials: A
authors.lastname: Covaci
authors.affiliation: Toxicological University of Antwerp, Universiteitsplein 1, B2610 Antwerp, Belgium.
authors.forename: Cleo L
authors.initials: CL
authors.lastname: Crunelle
mesh_terms: D000437:Alcoholism / Q000175:diagnosis; D015415:Biomarkers / Q000032:analysis; D002849:Chromatography, Gas / Q000379:methods*; D053593:Forensic Toxicology / Q000379:methods; D005965:Glucuronates / Q000032:analysis*; D006197:Hair / Q000737:chemistry*; D006801:Humans; D057230:Limit of Detection; D013058:Mass Spectrometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D015415:Biomarkers; D005965:Glucuronates; C093924:ethyl glucuronide
keywords: Alcohol; Ethyl glucuronide; GC–MS/MS; Hair; Negative ion chemical ionization; Validation