Drug abuse; Drug testing; GHB; Hair; Method validation; Sodium Oxybate; Female; Forensic Toxicology/methods; Gas Chromatography-Mass Spectrometry; Hair/chemistry; Healthy Volunteers; Humans; Male; Reproducibility of Results; Sodium Oxybate/analysis; Solid Phase Extraction; Substance Abuse Detection/methods; Substance-Related Disorders/diagnosis; Forensic Toxicology; Substance Abuse Detection; Substance-Related Disorders; Pathology and Forensic Medicine; Law
Abstract :
[en] Gamma-hydroxybutyric acid (GHB) is a short-chain fatty acid used recreationally as a drug of abuse due its strong suppressive effect on the central nervous system. The detection window of GHB in blood and urine is very narrow (t1/2=30min) but can be substantially prolonged using alternative matrices such as hair. We here present a newly developed and limited validated method with a solid phase extraction (SPE) using GC-MS/MS to determine concentrations of GHB in hair samples. The soft extraction technique (water and 90min ultrasonic bath) preserves GHB with a high yield and clean extracts. In addition, endogenous GHB can be detected in hair of non-GHB users. However, little is known about GHB concentrations in hair of abstinent, frequent and chronic GHB users. Therefore, we present data from hair samples of healthy volunteers to evaluate the proposed endogenous GHB ranges, and from GHB-dependent patients to address GHB concentrations in hair with GHB intake. In 20 non-GHB users, a mean endogenous concentration of 1.1±0.6ng/mg hair (range of 0.3-2ng/mg) was found. In GHB-dependent patients, concentrations between 6.3-239.6ng/mg hair were found, with no correlation between concentrations in hair and dose of GHB intake. In summary, we present a new and limited validated method, adequately sensitive for the detection of GHB in hair, as well as first-time measurements of GHB concentrations in dependent patients in order to better understand the relationship between the frequency of use/dose and concentrations observed in hair samples.
Disciplines :
Chemistry
Author, co-author :
Van Elsué, Nicolas; Toxicological Center, Antwerp University, Antwerp, Belgium. Electronic address: nicovanelsue@gmail.com
Verbrugge, Cor A; Novadic-Kentron, Network for Addiction Treatment Services, Vught, The Netherlands
van Baarle, Kim; Novadic-Kentron, Network for Addiction Treatment Services, Vught, The Netherlands
Rodrigues, Anaïs ; Université de Liège - ULiège > Molecular Systems (MolSys) ; Laboratoire National de Santé, Service de Toxicologie, Dudelange, Luxembourg
Neels, Hugo; Toxicological Center, Antwerp University, Antwerp, Belgium
Yegles, Michel; Laboratoire National de Santé, Service de Toxicologie, Dudelange, Luxembourg
Language :
English
Title :
Gammahydroxybutyrate in hair of non-GHB and repeated GHB users: A new and optimized method.
Busardo, F.P., Jones, A.W., GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome. Curr. Neuropharmacol. 13:1 (2015), 47–70, 10.2174/1570159X13666141210215423.
Andresen, H., Stimpfl, T., Sprys, N., Schnitgerhans, T., Muller, A., Liquid ecstasy — a significant drug problem. Dtsch. Arztebl. Int. 105:36 (2008), 599–603, 10.3238/arztebl.2008.0599.
Stein, L.A., Lebeau, R., Clair, M., et al. A web-based study of gamma hydroxybutyrate (GHB): patterns, experiences, and functions of use. Am. J. Addict. 20:1 (2011), 30–39, 10.1111/j.1521-0391.2010.00099.x.
Kintz, P., Cirimele, V., Jamey, C., Ludes, B., Testing for GHB in hair by GC/MS/MS after a single exposure. Application to document sexual assault. J. Forensic Sci. 48:1 (2003), 195–200.
Johansen, S.S., Wang, X., Sejer Pedersen, D., et al. Gamma-Hydroxybutyrate (GHB) content in hair samples correlates negatively with age in succinic semialdehyde dehydrogenase deficiency. JIMD Rep. 36 (2017), 93–98, 10.1007/8904_2017_3.
Goulle, J.P., Cheze, M., Pepin, G., Determination of endogenous levels of GHB in human hair. Are there possibilities for the identification of GHB administration through hair analysis in cases of drug-facilitated sexual assault?. J. Anal. Toxicol. 27:8 (2003), 574–580.
Kintz, P., A novel approach to document single exposure to GHB: hair analysis after sweat contamination. J. Anal. Toxicol. 40:7 (2016), 563–564, 10.1093/jat/bkw052.
Mehling, L.M., Wang, X., Johansen, S.S., et al. Determination of GHB and GHB-beta-O-glucuronide in hair of three narcoleptic patients — comparison between single and chronic GHB exposure. Forensic Sci. Int. 278 (2017), e8–e13, 10.1016/j.forsciint.2017.07.027.
Kintz, P., Villain, M., Cirimele, V., Ludes, B., GHB in postmortem toxicology. Discrimination between endogenous production from exposure using multiple specimens. Forensic Sci. Int. 143:2–3 (2004), 177–181, 10.1016/j.forsciint.2004.02.036.
Haller, C., Thai, D., Jacob, P. 3rd., Dyer, J.E., GHB urine concentrations after single-dose administration in humans. J. Anal. Toxicol. 30:6 (2006), 360–364.
Moriya, F., Hashimoto, Y., Site-dependent production of gamma-hydroxybutyric acid in the early postmortem period. Forensic Sci. Int. 148:2–3 (2005), 139–142, 10.1016/j.forsciint.2004.05.002.
Schrock, A., Hari, Y., Konig, S., Auwarter, V., Schurch, S., Weinmann, W., Pharmacokinetics of GHB and detection window in serum and urine after single uptake of a low dose of GBL — an experiment with two volunteers. Drug Test. Anal. 6:4 (2014), 363–366, 10.1002/dta.1498.
Vaiano, F., Serpelloni, G., Furlanetto, S., et al. Determination of endogenous concentration of gamma-hydroxybutyric acid (GHB) in hair through an ad hoc GC–MS analysis: a study on a wide population and influence of gender and age. J. Pharm. Biomed. Anal. 118 (2016), 161–166, 10.1016/j.jpba.2015.10.036.
Shi, Y., Cui, X., Shen, M., Xiang, P., Quantitative analysis of the endogenous GHB level in the hair of the Chinese population using GC/MS/MS. J. Forensic Leg. Med. 39 (2016), 10–15, 10.1016/j.jflm.2016.01.002.
Bertol, E., Mari, F., Vaiano, F., et al. Determination of GHB in human hair by HPLC-MS/MS: development and validation of a method and application to a study group and three possible single exposure cases. Drug Test. Anal. 7:5 (2015), 376–384, 10.1002/dta.1679.
Hari, Y., König, Stefan, Schröck, A., Coro, P., Auwärter, V., Thierauf, A., Weinmann, W., LC–MS/MS of GHB in head hair and beard. Toxichem Krimtech 80 (2013), 224–227.
Bertol, E., Argo, A., Procaccianti, P., et al. Detection of gamma-hydroxybutyrate in hair: validation of GC–MS and LC–MS/MS methods and application to a real case. J. Pharm. Biomed. Anal. 70 (2012), 518–522, 10.1016/j.jpba.2012.07.009.
Kerekes, I., Yegles, M., Coloring, bleaching, and perming: influence on EtG content in hair. Ther. Drug Monit. 35:4 (2013), 527–529, 10.1097/FTD.0b013e31828ca246.
Villain, M., Cirimele, V., Ludes, B., Kintz, P., Ultra-rapid procedure to test for gamma-hydroxybutyric acid in blood and urine by gas chromatography–mass spectrometry. J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 792:1 (2003), 83–87.
Crunelle, C.L., Yegles, M., De Doncker, M., et al. Influence of repeated permanent coloring and bleaching on ethyl glucuronide concentrations in hair from alcohol-dependent patients. Forensic Sci. Int. 247 (2015), 18–22, 10.1016/j.forsciint.2014.11.023.