GHB and GBL

Formlmorphology/exhibits Classification Medical uses Color test Microscopic/Crystal tests Other tests  

Exhibits suspected to contain GHB or related substances are often received as a liquid, either a suspect beverage or in concentrated form. Powders may 

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As discussed previously, the absorption of GBL has been documented to occur faster than GHB. It has also been proposed that in addition to the better absorption of GBL, it may also distribute differently than GHB. An early study comparing the distribution of equimolar doses of GHB and GBL in rats found that although peak plasma concentrations were higher with GHB they remained elevated longer with GBL. In addition, concentrations of GBL in the lean muscle mass of the rat were always elevated compared with concentrations of GHB (Roth and Giarman, 1966). This suggests sequestration of GBL into lean muscle prior to its conversion to GHB. Since lean muscle does not contain the lactonase enzyme, it is conceivable that this could occur. The GBL could then redistribute into the blood to be... 

Prison et al. (1998) describes a method using sohd-phase microextraction of GHB in plasma and urine. This is a new approach for GHB analysis that shows promise in that it is simple, sensitive and requires only 0.5 mL of specimen. The linearity range was from 1 to 100 pg mL in plasma and from 5 to 150 pg mL in urine with a Emit of detection of 0.05 and 0.1 pg mL for plasma and urine, respectively. The limit of detection was calculated based on aqueous solutions because the blank plasma and urine specimens had endogenous GHB concentrations of 0.1-0.2 and 0.5-L5pgmL, respectively. The method required conversion of GHB to GBL with GBL-de as the internal standard and detection by headspace GC-MS with spectra from both CI and El ionization modes. Many methods are available for GHB and GBL analyses depending on the equipment and resources available to the laboratory. 

Ciolino, L.A., and Mesmer, M.Z. (2000). Bridging the gap between GHB and GBL - forensic issues of interconversion. American Academy of Forensic Science Annual Meeting, Reno, NV, Abstract B51. 

Figure 7.28 Structures of 1.4-butanediol, GHB, and GBL, the corresponding lactone. Conversion between GHB and GBL depends primarily on pH. 

One test occasionally performed on aqueous solutions containing a mixture of GHB and GBL is a test for elevated concentrations of K or Na . Why ... 

Ciolino, L. A., et al. "The Chemical Interconversion of GHB and GBL Forensic Issues aind Implications." Journal cf Forensic Sciences, 46 2001,1315-1323. 

McDaniel CH, Miotto KA Gamma hydroxybutyrate (GHB) and gamma butyrolac-tone (GBL) withdrawal five case studies. J Psychoactive Drugs 33 143—149,2001... 

After GHB was banned by the FDA in 1990 for over-the-counter use, GHB chemists tried to circumvent the ban by developing closely related chemicals called gamma butyrolactone (GBL) and 1,4-butanediol (BD). The chemical structures of GHB, GBL, and BD are shown in Figure 4.1. When GBL or BD is ingested, it is rapidly converted by the body to form GHB, and the effects become identical to that of taking regular GHB. Due to the 1990 FDA ban, manufacturers of nutritional supplements previously selling GHB quickly reformulated their product so it contained GBL and/or BD instead of the... 

Le Beau MA, Montgomery MA, Miller ML, Burmeister SG. 2000. Analysis of biofluids for gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) by headspace GC-FID and GC-MS. J Anal Toxicol 24 421. 

GBL and related drugs, GHB and BD, are illegal substances and currently have no approved medical indications in the United States. 

From January 1999 to August 2000, the FDA received 48 reports of acute BD intoxication, including loss of consciousness, dangerously low respiratory rates, vomiting, and slowed heartbeat. In a series of nine toxic reactions to BD reported in the New England Journal of Medicine in early 2001, the effects of BD were similar to those of GBL and GHB, and included addiction, withdrawal, and death. 

Overall, the DEA has reported more than 72 deaths and 5,500 emergency room overdoses associated with GHB, and serious ill effects related to GBL and related drugs, GHB and BD, in at least five children under 18 years of age. All five children had vomiting and became unconscious, and most had respiratory depression and dangerous slowing of heart rate. As GBL crosses the placenta, a pregnant woman exposes her unborn baby to its dangerous effects. 

On February 18, 2000, the Hillary Farias and Samantha Reed Date-Rape Prohibition Act (Public Law 106-172) made the GHB precursor GBL a List I chemical, subject to the criminal, civil, and administrative sanctions of the Controlled Substances Act. On March 13, 2000, GHB became a Schedule I controlled substance (65 FR 13235-13238), subject to the regulatory controls and the criminal, civil, and administrative sanctions of the Controlled Substances Act. Schedule I, which is the same as for heroin, LSD, and marijuana, states that the drug has no medical use and cannot be prescribed, and that the drug has a high potential for abuse. 

GBL was found to hydrolyse rapidly in plasma, with a half-life of approximately 1 minute. In spite of this rapid biotransformation, oral activity of GBL was almost identical to that achieved after intravenous administration of GHB. Apparently, GBL is not subjected to any of the processes which decrease peak plasma concentrations, viz gastrointestinal degradation, capacity-limited transport and first-pass metabolism. The use of lactone analogs as a general approach to improve the bioavailability and/or rate of absorption of other hydroxy-acids, e.g. prostaglandins, has, however, not been tested. 

GHB does not exist in a static state, even outside the body. In solution, it exists in a dynamic state in equilibrium with its lactone, GBL (Figure 11.2). The ratio of the two forms is dependent on the pH of the matrix or the type of matrix containing the GHB. For example, in blood, the GHB acid form predominates because the lactonase enzyme converts any of the lactone to the acid. However, if the GHB is in a matrix that does not contain this enzyme, such as urine, water or juice, the two forms will reach equilibrium. The pA aS for GHB and 4-Me-GHB are 4.72 and 5.72, respectively, therefore the lactone form predominates at pH below these values and the acidic or salt form predominates above these values. Complete conversion to GBL is favored in dehydrating conditions in a concentrated acid solution (pH < 2). The rate at which the equilibrium is achieved depends on the temperature and the actual pH of the matrix. 

Biological specimen extraction can be accomplished by liquid-liquid, solid-phase or solid-phase microextraction with subsequent detection of GHB or GBL by gas chromatography-mass spectrometry (GC-MS) using electron ionization (El), positive or negative chemical ionization (CI) or gas chromatography with flame ionization detection (GC-FID). LeBeau et al. (1999) describes a method that employs two ahquots of specimen. The first is converted to GBL with concentrated sulfuric acid while the second is extracted without conversion. A simple liquid-liquid methylene chloride extraction was utilized, and the ahquots were then screened by GC-FID without derivatization. Specimens that screened positive by this method were then re-aliquoted and subjected to the same extraction with the addition of the deuterated analog of GBL. The extract was then analyzed by headspace GC-MS in the full-scan mode. Quantitation was performed by comparison of the area of the... 

Anderson, D.T., Muto, J.J. and Andrews, J.M. (2000). Case report postmortem tissue distribution of gamma hydroxybutyrate (GHB) and gamma butyrolactone (GBL) in a single fatality. Program and Abstracts of the Society of Forensic Toxicologists Annual Meeting, Milwaukee, WI, Poster 37. 

Describe the potential health hazards involved with the administration of gamma buty-rolactone (GBL), gamma hydroxybutyric acid (GHB), and 1,4-butanediol (BD). 

GHB has been used both for legitimate clinical and chnical research purposes and for a range of iUicit purposes. It was marketed legally in the United States until 1990, when the U.S. Food and Drug Administration (FDA) banned its sale to consumers. Except for the one indication described later in this section, GHB is a Schedule I controlled substance without other FDA-approved indications. The FDA has also declared y-butyrolactone (GBL) as a List I chemical and 1,4-butanediol (1,4-BD) as a Class I health hazard, practically designating these GHB precursors, which are also industrial solvents, as illicit and unapproved new drugs (National Institute on Drug Abuse 2000). 

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