Do drug users use less alcohol than non-drug users? A comparison of ethyl glucuronide concentrations in hair between the two groups in medico-legal cases

Paul, Richard; Kingston, R. H.; Tsanaclis, Lolita; Berry, Antony J.; Guwy, Alan J.

doi:10.1016/j.forsciint.2007.06.025

Cited by 47 publications

(26 citation statements)

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“…Paul et al (2008) compared the mean concentration of EtG in hair samples between a group of narcotic and drug consumers (opiates, cocaine, amphetamines, methamphetamine, benzodiazepines, and cannabis) and a group of non-consumers. The mean concentration of EtG was significantly higher in the drugnegative group than that found in the drug-positive group (0.107 versus 0.011 ng/mg; P , 0.05) (Paul et al, 2008). To better understand such possible interactions, we used pooled HLM to perform in vitro co-incubations of ethanol with various compounds frequently used by alcohol consumers.…”

Section: Discussionmentioning

confidence: 99%

“…However, considering the numerous factors that could affect glucuronidation (e.g., genetic polymorphisms, inhibition or induction by xenobiotics, and age), the relevance of these cutoffs in clinical and forensic practices can be questioned in certain circumstances (Kiang et al, 2005). Some reports have indeed documented a high interindividual variability in EtG production (Halter et al, 2008;Paul et al, 2008). Halter et al (2007) showed that the administration of a conventional dose of ethanol to 13 individuals resulted in highly variable (8-fold) maximum concentrations of serum EtG, and that EtG concentrations did not correlate with blood ethanol concentrations (Halter et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

et al. 2012

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Ethyl glucuronide (EtG) determination is increasingly used in clinical and forensic toxicology to document ethanol consumption. The enzymes involved in EtG production, as well as potential interactions with common drugs of abuse, have not been extensively studied. Activities of human liver (HLM), kidney (HKM), and intestinal (HIM) microsomes, as well as of 12 major human recombinant UDP-glucuronosyltransferases (UGTs), toward ethanol (50 and 500 mM) were evaluated in vitro using liquid chromatography-tandem mass spectrometry. Enzyme kinetic parameters were determined for pooled microsomes and recombinant UGTs with significant activity. Individual contributions of UGTs were estimated using the relative activity factor approach, proposed for scaling activities obtained with cDNA-expressed enzymes to HLM. Interaction of morphine, codeine, lorazepam, oxazepam, nicotine, cotinine, cannabinol, and cannabidiol (5, 10, 15 mg/l) with ethanol (1.15, 4.6, 11.5 g/l; i.e., 25, 100, 250 mM) glucuronidation was assessed using pooled HLM. Ethanol glucuronidation intrinsic clearance (Cl int ) was 4 and 12.7 times higher for HLM than for HKM and HIM, respectively. All recombinant UGTs, except UGT1A1, 1A6, and 1A10, produced EtG in detectable amounts. UGT1A9 and 2B7 were the most active enzymes, each accounting for 17 and 33% of HLM Cl int , respectively. Only cannabinol and cannabidiol significantly affected ethanol glucuronidation. Cannabinol increased ethanol glucuronidation in a concentrationdependent manner, whereas cannabidiol significantly inhibited EtG formation in a noncompetitive manner (IC 50 = 1.17 mg/l; inhibition constant (K i ) = 3.1 mg/l). UGT1A9 and 2B7 are the main enzymes involved in ethanol glucuronidation. In addition, our results suggest that cannabinol and cannabidiol could significantly alter ethanol glucuronidation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

et al. 2012

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“…This LOD value is considerably 612 higher than the established cut-off limit to evidence alcohol use disorders (Kintz, 2012b). spectrometer, and SRM (Paul et al, 2008). The instrumental analysis followed water extraction,…”

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confidence: 91%

“…LOD of 5 pg/mg was obtained, and the chromatography cycle was 7.30 min (Paul et al, 2008). A 620 modified protocol was reported by the same group in 2011, in which the SRM transitions for GHB 621 were added to the same analytical protocol, so as to detect EtG and GHB within a single 622 chromatographic procedure.…”

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confidence: 99%

“…The authors suggested that, upon optimization of streaming volume, purge time, 627 programmable temperature vaporization (PTV) temperature, injection volume, and other 628 experimental parameters, the detection capability can be improved by at least 1-2 orders of 629 magnitude, as compared to the traditional approach (Shi et al, 2010). Even so, they estimated an 630 LOD value of 5 pg/mg, with 20 mg of hair, as in the method previously cited (Paul et al, 2008).…”

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confidence: 99%

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Application of mass spectrometry to hair analysis for forensic toxicological investigations

Vincenti

Salomone²,

Gerace³

et al. 2012

Mass Spectrometry Reviews

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The increasing role of hair analysis in forensic toxicological investigations principally owes to recent improvements of mass spectrometric instrumentation. Research achievements during the last six years in this distinctive application area of analytical toxicology are reviewed. The earlier state of the art of hair analysis was comprehensively covered by a dedicated book (Kintz, 2007a), that represents key reference of the present overview. Whereas the traditional organization of analytical methods in forensic toxicology divided target substances into quite homogeneous groups of drugs, with similar structures and chemical properties, the current approach often takes advantage of the rapid expansion of multiclass and multiresidue analytical procedures; the latter is made possible by the fast operation and extreme sensitivity of modern mass spectrometers. This change in the strategy of toxicological analysis is reflected in the presentation of the recent literature material, which is mostly based on a fit-for-purpose logic. Thus, general screening of unknown substances is applied in diverse forensic contexts than drugs of abuse testing, and different instrumentation (triple quadrupoles, time-of-flight analyzers, linear and orbital traps) is utilized to optimally cope with the scope. Other key issues of modern toxicology, such as cost reduction and high sample throughput, are discussed with reference to procedural and instrumental alternatives.

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The role of alternative specimens in toxicological analysis

Gallardo

Queiroz

2008

Biomedical Chromatography

164

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The use of alternative specimens in the field of toxicology was first described in 1979, when hair analysis was used to document chronic drug exposure. Since then, the use of these 'alternative' samples has gained tremendous importance in forensic toxicology, as well as in clinic toxicology, doping control and workplace drug testing. It is not surprising, therefore, that a large number of papers dealing with the determination of several classes of drugs in saliva, sweat, meconium and hair have been published ever since, owing to the fact that chromatographic equipment is becoming more and more sensitive, mass spectrometry (and tandem mass spectrometry) being the most widely used analytical tool, combined with gas or liquid chromatography. 'Alternative' specimens present a number of advantages over the 'traditional' samples normally used in toxicology (e.g. blood, urine and tissues), namely the fact that their collection is not invasive, their adulteration is difficult, and they may allow increased windows of detection for certain drugs. The main disadvantage of this kind of samples is that drugs are present in very low concentrations, and therefore high-sensitivity techniques are required to accomplish the analysis. This paper reviews a series of publications on the use of alternative specimens, with special focus on the main analytical and chromatographic problems that these samples present, as well on their advantages and disadvantages over traditional samples in documenting drug exposure.

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Do drug users use less alcohol than non-drug users? A comparison of ethyl glucuronide concentrations in hair between the two groups in medico-legal cases

Cited by 47 publications

References 12 publications

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

Involvement of UDP-Glucuronosyltransferases UGT1A9 and UGT2B7 in Ethanol Glucuronidation, and Interactions with Common Drugs of Abuse

Application of mass spectrometry to hair analysis for forensic toxicological investigations

The role of alternative specimens in toxicological analysis

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