Gamma-hydroxybutyrate (NaGHB) is a central nervous system depressant originally used as an anesthetic adjunct in Europe more than 30 years ago (1) (Fig. 1). It is known to promote the release of growth hormones and was used both for muscle growth and as a sleep aid among bodybuilders during the 1980s (2,3). In 1989, NaGHB abuse began to increase due to its marketing as the replacement for L-tryptophan (4). In early 1990, hospital emergency rooms across the United States reported numerous cases of NaGHB overdose and related poisoning episodes (5), prompting several states to ban over-the-counter sales of NaGHB and NaGHBcontaining "supplements" in 1990. Following the ban, NaGHB was manufactured clandestinely from gamma-butyrolactone (GBL) (Fig. 2). NaGHB is currently abused for its hypnotic and euphoric effects and is commonly encountered at "rave parties" and in drug-aided sexual assault cases. There has been a widespread increase of NaGHB-related emergency room visits with 56 recorded visits in 1994 to 4969 visits in 2000 (6). On February 18, 2000, the Hillory J. Farias and Samantha Reid Date-Rape Drug Prohibition Act of 1999 (Public Law 106-172) was signed and became Federal law. This law directed DEA to place GHB into Schedule I of the Controlled Substances Act (CSA). The final rule issued by DEA became effective on March 13, 2000 (the same day it was published in the Federal Register). It also placed GBL as a List I chemical. If, however, GBL is intended for human consumption and meets the definition of a Controlled Substance Analog in the CSA (21 USC 802(32), it could be treated as a Schedule I Controlled Substance. GHB-containing products manufactured, distributed or possessed in accordance with FDA authorized Investigational New Drug exemptions under the Federal Food, Drug and Cosmetic Act are placed into Schedule III, if or when they are approved. The common means of identification of NaGHB involves using FTIR or derivatization followed by GC-MS. However, samples containing mixtures of NaGHB, GBL and/or other impurities require cleanup procedures such as acid/base extraction followed by evaporation of excess water prior to FTIR determination (7,8). Because NaGHB converts to GBL in heated injection ports, the identification of the original material by GC or GC-MS cannot be attempted without preliminary derivatization (9,10). In addition, sample preparation can affect the outcome of the analysis. The interconversion between NaGHB and GBL (Fig. 3) is very pH dependent, and any equilibrium shift during cleanup and derivatization can pose problems in the analysis (11). Although the lactone cannot be directly derivatized, in some cases, low levels of lactone may convert into GHB and then be derivatized. This has been detected in some derivatization experiments in the DEA Western laboratory using trimethylsilylating agents. High Pressure Liquid Chromatography/Ultraviolet-Visible Spectrophotometry (HPLC/ UV-VIS), and HPLC/thermospray mass spectrometry have been used for separation and quantitation of GHB, and the ...
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