You are on page 1of 7

Chapter 49

Detection of GHB by Optical Methods


Wang Xu1,2, Duanting Zhai1, Young-Tae Chang1,3
1Department of Chemistry & MedChem Program of Life Sciences Institute, National University of Singapore, Singapore; 2Singapore Peking Oxford
Research Enterprise (SPORE), NUS Environmental Research Institute (NERI), Singapore; 3Singapore Bioimaging Consortium, Agency for Science,
Technology and Research (A*STAR), Singapore

Abbreviations even death (Ropero-Miller & Goldberger, 1998). It was banned


for sale as a supplement in the United States by the FDA in 1990,
AO  Acridine orange and subsequently classified as a Schedule 1 drug by the Controlled
CNS  Central nervous system Substances Act in March 2000. The only remaining medical appli-
DFSA  Drug-facilitated sexual assault cation of GHB in the current time is the treatment of narcolepsy
DMSO  Dimethyl sulfoxide and alcoholism.
GABA  Gamma-aminobutyric acid Since the mid-1990s, GHB has been labeled with a notorious
GBL  Gamma-butyrolactone name—date rape drug—due to its intense usage in drug-facili-
GC  Gas chromatography tated sexual assault (DFSA). As a supplement or drug, GHB is
GHB  Gamma-hydroxybutyric acid most commonly used in the form of salt such as sodium GHB
HPLC  High-performance liquid chromatography or potassium GHB, both of which are white crystalline pow-
IR  Infrared spectroscopy der; or it can be treated as clear aqueous solution of GHB salt.
MB  Methylene blue GHB is sold on the streets under many names, such as G, Liq-
MS  Mass spectrometry uid X, Liquid E, Liquid G, Salty Water, Fantasy or Juice, Mils,
NMR  Nuclear magnetic resonance Scoop or Soap, Liquid Ecstasy, etc. Apart from GHB itself, its
OX  Oxonine prodrugs such as gamma-butyrolactone (GBL) (Figure 1) and
PET  Photoinduced electron transfer 1,4-butanediol have also been deemed as date rape drugs (Mason
PF  Proflavine & Kerns, 2002). GBL and 1,4-butanediol are intrinsically inac-
PYY  Pyronine Y tive under the pharmacological condition; however, they can be
RGB  Red–green–blue easily metabolized to GHB inside the human body (Lettieri &
TH  Thionine Fung, 1978). This brings additional concerns with these prodrugs
because they are widely used as industrial solvents and legiti-
mate chemical reagents (Shannon & Quang, 2000). GHB can
INTRODUCTION be easily prepared even with very little knowledge of chemistry.
Gamma-hydroxybutyric acid (GHB) (Figure 1) is a naturally The preparation involves simple mixing of two precursors, GBL
occurring substance found in small amounts in almost all living and sodium/potassium hydroxide, to form the resulting GHB
species, residing in their central nervous system (CNS) (Bessman & salt. Due to the ready availability of its precursors and simple
Fishbein, 1963). As a metabolite of gamma-aminobutyric acid one-step chemistry, manufacturing GHB can even be carried out
(GABA), GHB is involved in the regulation of multiple neurotrans- in a home laboratory. Small amounts of GHB (less than 1 g to a
mitters, including GABA, dopamine, 5-hydroxytryptamine, and normal human) act as a relaxant that causes loss of muscle tone
acetylcholine (Mamelak, 1989). GHB depresses the CNS through and reduced inhibitions. At scales larger than 1 g, GHB slows
the induction of reversible coma and deep sleep; therefore, it down heart rate and respiration (1–2 g to a normal human) or
was first medically introduced in 1960 as a general anesthetic interferes with motor and speech control which induces a coma-
(Galloway et al., 1997). Subsequently, GHB was further applied like sleep (2–4 g to a normal human), or ultimately leads to death
to a variety of purposes, including fat reduction and muscle devel- (larger than 4 g to a normal human) (Lesar, Decatur, Lukasiewicz, &
opment, improvement of athletic performance, and treatment Champeil, 2011; Sumnall et al., 2008). GHB takes effect within
of sleep disorders and depression (Sumnall, Woolfall, Edwards, 15–30 min and could last as long as 3–6 h. It can only be
Cole, & Beynon, 2008). However, GHB can induce negative detected in urine samples within a period of 6–12 h after inges-
phenomena at higher doses or together with alcohol. Adverse effects tion (Brailsford, Cowan, & Kicman, 2012), yet unfortunately
include visual disturbance, memory impairment, respiratory arrest GHB-induced memory impairment often elongates the time that
and nausea, vomit, dizziness and drowsiness, amnesia, coma, or many victims need to recall the scene of rape. What is worse is

Neuropathology of Drug Addictions and Substance Misuse, Volume 2. http://dx.doi.org/10.1016/B978-0-12-800212-4.00049-2


Copyright © 2016 Elsevier Inc. All rights reserved. 529
530  PART | II  Club Drugs

A COLORIMETRIC SENSOR ARRAY


FOR THE DETECTION OF GHB
In supramolecular approach, host–guest interaction is favored to
FIGURE 1  Structures and chemistry of GHB and GBL. Structures of achieve molecular recognition especially for small-molecule ana-
GHB and GBL. Chemical and Biological formation from GBL to GHB. lytes. Baumes et al. (2010) developed a dual-response colorimet-
ric/fluorometric sensor array for the detection of GHB based on
supramolecular host–guest complexes by combining six fluores-
that given GHB’s odorless and colorless physical properties, it cent dyes as guests and two cucurbiturils as hosts (Figure 2). In
is practically undetectable when mixed with an alcoholic drink. this approach, multiwell plates were prefilled with capsule solu-
Hence, as a result, due to ready availability, fast elimination after tions and dye solutions. After addition of the GHB aqueous solu-
ingestion, colorless and odorless properties, and good solubil- tion, images of the plate were taken using a dark chamber with a
ity in aqueous/alcoholic solutions, GHB is deemed as the most set of UV (355 nm) lamps and transferred to a personal computer
notorious date rape drug desirable to sexual predators (Nemeth, (PC) to extract the red–green–blue (RGB) components. The values
Kun, & Demetrovics, 2010). of these RGB components were thus analyzed to render quantita-
Traditionally, GHB detection was solely based on complicated tive values of GHB concentrations. Through this assay, researchers
laboratory instruments and usually requires a series of preparation were able to detect the presence of GHB of concentrations above
steps. Typical examples include tandem gas chromatography (GC) 100 μM. Further selectivity test of the sensor concluded a discrimi-
separation and mass spectrometry (MS) detection, which requires nation of GHB against a series of related compounds, including
acidification of blood samples of victims with 0.1 N H2SO4, subse- GBL, 1,4-butanediol, propionic acid, and butyric acid. Mecha-
quent extraction with ethyl acetate, followed by injection into the nism studies have revealed that the response arises from the color
instrument (McCusker, Paget-Wilkes, Chronister, & Goldberger, changes depending on dye aggregation and solvatochromism.
1999). Diethylene glycol was often used as an internal standard. To facilitate the usage of this GHB assay sensor, we hereby
GHB was derivatized to its trimethyl silane derivative using N,O- summarize the protocol of this sensor array as listed below.
Bistrifluoroacetamide/1% trimethylsilyl chloride. This assay
method exhibits a detection limit of 1 mg/l (Couper & Lorgan,
2004). On the other hand, a high-performance liquid chromatogra-
phy (HPLC)-based method has been reported for GHB detection. Materials:
Samples were separated through reverse phase HPLC and detected Fluorescent dyes (386 μM): methylene blue (MB), t­hionine
using ultraviolet (UV) detection at 215 nm. Confirmation of GHB (TH), oxonine (OX), pyronine Y (PYY), acridine orange (AO),
species was given by thermospray MS (Ciolino et al., 2001). Simi- and proflavine (PF).
larly, infrared spectroscopy (IR) has also been used to detect GHB; Capsules (100 μM): CB[7] and CB[8].
yet it only delivers qualification data instead of quantitative results. Protocol:
Given the instruments required in the detection process, all the 1. Fill each well of the multiwell plates with 239 μl of ­capsule
methods stated above can only be performed in analytical laborato- solution plus 70 μl of dye solution.
ries with well-trained personnel, i.e., in the case of forensic samples 2. Add 30 μM of GHB solution in water to each well.
of presumed victims where tragedies have already taken place. As a 3. Transferred plates to a dark chamber and illuminate with
matter of fact, the rapid increase of GHB involved in DFSA crime white light or UV lamps (355 nm).
cases seriously calls for a rapid and convenient field testing method 4. Take images with a 6.1 megapixel CCD Nikon D50
that facilitates the detection of GHB before ingestion. camera.
Recent efforts on rapid GHB detection by both research insti- 5. Transfer images were transferred to a PC to digitalize the
tutes and companies have seen the hope of its on-field diagnostics. image, extract, and store the RGB component.
Garcia et al. reported a colorimetric sensor array for the detection of
GHB based on supramolecular host–guest complexes of fluorescent
dyes with organic capsules (Baumes, Buaki Sogo, Montes-Navajas,
Corma, & Garcia, 2010). Chang et al. reported the first fluores- A FLUORESCENT SENSOR FOR
cent sensor for the prodrug GBL in 2013 (Zhai et al., 2013) and THE DETECTION OF GHB
subsequently they developed the first fluorescent sensor for GHB
itself (Zhai, Tan, Xu, & Chang, 2014), both of which were based on Fluorescent sensors are attractive sensing tools owing to their
BODIPY structure. On the other hand, commercial products were high sensitivity, fast response, and technical simplicity. Zhai
also developed and launched into the market, such as “DrinkSafe™” et al. (2014) reported the first fluorescent sensor for the illicit
cards, “DrinkSafe™” coasters, and “Drink Detective™” test kits date rape drug GHB (Figure 3). In Prof. Young-Tae Chang’s
from Drink Safe Technology®, Scott kit from Scott Company®, and group, a series of diversity-oriented fluorescent libraries have
EZ Test kit for GHB from EZ Test Kits®. In this chapter, we will been designed and synthesized, which contain thousands of fluo-
summarize all the currently available assay sensors for GHB/GBL rescent dyes. Through an image-based high-throughput screen-
and elucidate their sensing modes. We sincerely hope that this will ing platform using 5500 fluorescent compounds, the authors
inspire following work on the rapid detection of date rape drugs and identified a BODIPY structure, GHB Orange (Figure 3(A)), as
finally prevent its usage in DFSA cases. the first small molecule GHB fluorescent sensor. GHB Orange
Assay Sensor for GHB Chapter | 49  531

FIGURE 2  Supramolecular GHB detection paradigm. Images of a plate in the absence of analyte taken under white light or monochromatic UV
(355 nm) light. Left: original image; right: digitalized image. Two views of CB[7] capsule are shown on the top right. Adapted with permission from
Baumes et al. (2010). Copyright 2000 Wiley-VCH.

showed a fluorescent quenching response in the presence of GHB In this work, the interaction mechanism between GHB
(Figure 3(B)). With addition of GHB, the intrinsic bright orange Orange and GHB was explored by nuclear magnetic resonance
fluorescent color could be quenched dramatically to a dark state. (NMR) spectroscopy, which showed that protons in GHB Orange
Proper optimization of the sensing event was also conducted by shifted up-field upon increasing equivalents of GHB. This indi-
the researchers and the working condition was confirmed to be cated the formation of a hydrogen bond between GHB Orange and
50% dimethyl sulfoxide (DMSO) aqueous solution with a 5.5- GHB, which enhanced photo-induced electron transfer effect of
fold fluorescence decrease at 10 mg/ml GHB, which is the nor- the fluorophore and quenched its fluorescence.
mal GHB spiking amount. More importantly, GHB Orange was A protocol of this sensor is listed below.
further applied to test GHB in a large variety of beverages rep-
resenting alcoholic, nonalcoholic, colored, and colorless drinks.
The detection process was optimized as a simple mix-and-see Materials:
procedure. Explicit intensity change was observed under the irra- GHB Orange DMSO solution (100 μM)
diation of a handheld 365 nm lamp (Figure 3(D)). This is a clear Protocol:
sign of application possibility because 365 nm UV light is readily 1. Mix the GHB Orange solution with GHB analyte
available in most of the bars where DFSA takes place. Thus one ­solution in a 1:1 ratio by volume.
plausible usage of the sensor was to develop it into nail polish 2. Visualize the mixture with a 365 nm UV lamp or green
or similar styles of carriable stuff that one can readily apply to laser.
drink testing.
532  PART | II  Club Drugs

(A) (C) 10000 8


control
N N 9000 6

Fluorescence Intensity RFU


B

FO/ F
F F 4 3 mg/mL
8000
y = 0.063x + 1 5 mg/mL
DMSO,ΦF 0.86 7000 2
R2 = 0.976
Br λabs max 564 nm 0 10 mg/mL
6000
λflu max 587 nm 0 20 40 60 80 100
HO GHB Orange 5000 25 mg/mL
GHB Concentration / mg/mL
4000 50 mg/mL
(B) without with 3000 100 mg/mL
GHB GHB 2000
1000
0
560 580 600 620 640
(D) Wavelength / nm
water beer red wine vodca cola Korean soju apple juice whiskey

FIGURE 3  The sensing paradigm of GHB Orange and fluorescence responses. (A) Structure of GHB Orange. (B) Picture of GHB Orange solution
with and without GHB taken from the screening camera box. (C) Fluorescent spectra of GHB Orange after incubation with different concentrations of
GHB (inner). Linear correlation of fold change of fluorescence versus concentration of GHB. (D) Pictures of beverage samples with (right) and without
(left) GHB containing GHB Orange under irradiation using a handheld 365 nm lamp. Adapted with permission from Zhai et al. (2014). Copyright 2014
Royal Society of Chemistry.

COMMERCIAL KITS FOR THE DETECTION matrix, high concentration of the drugs required, and extensive
time required for ketamine analysis (Meyers & Almirall, 2004).
OF GHB
Studies also showed that this product performed much better in
There is an increasing public awareness and attention to DFSA. the laboratory than it did in the untrained hands of consumers
Fear of DFSA has generated a growing market for products that in the field. In fact, there is a possibility that consumers would
claim to be able to reduce potential victims’ vulnerability. These misinterpret a result and record a false-negative outcome (Quest
products allow customers to do in vitro field test for beverages & Horsley, 2007).
suspected of being drugged.

EZ Test Kits
Drink Safe Coaster EZ Test Kits is a company founded in the United Kingdom,
Drink Safe Technology (http://www.drinksafetech.com/) is the which sells test kits specifically for GHB (http://www.eztestkits.
best-known company launching products detecting GHB. Their com/en/ez-testing-kits/ghb-drug-testing-kit). The test kit uses
product, Drink Safe Coaster (http://store.drinksafetech.com/ a chemical reagent absorbed in silica gel that is held inside a
categories/), is an inexpensive color change test kit marketed glass ampoule. During the test, consumers were instructed to
internationally for customs to detect potentially incapacitating crack open the ampoule and drip in a small amount of the sam-
concentrations of GHB (complexed with either sodium or potas- ple. They then put the plastic lid on and shook it well to allow
sium ion) and another date rape drug, ketamine. Until now, mil- full reaction between the reagent and GHB. A color change took
lions of such coasters have been sold, which indicates the huge place if GHB was present in the sample. The customers could
market size. In the test, customers were directed to place one thus compare the changed color with the color chart provided
drop of beverage onto both spots of one test area, rub each spot on the instructions within the package. This product, however,
gently, and allow it to dry. If dark blue showed in either spot, has shown several disadvantages including complicated handling
it indicated detection of a possible date rape drug. However, process and a merely presumptive test result, as claimed by the
some beverages are not recommended for testing, including inventors themselves.
milk products, very acidic beverages, oily liquors, or any drinks
containing quinine. Research was conducted to study the effec-
tiveness of Drink Safe Coaster, which revealed that although
Scott Kit
Drink Safe Coaster was able to detect the presence of GHB and Scott Company has introduced a chemical colorimetric test for
ketamine, there were a series of limitations. Examples ranged GHB (http://www.scottcompany.com/∼shop/ghb-test/259375/).
from hindrance of the reaction due to complicated beverage During the test, a cotton bud is soaked in the GHB sample and
Assay Sensor for GHB Chapter | 49  533

then placed in a small vial containing their chemical reagents. Date, thus reducing the static quenching effect of Green Date and
Should the drink contain GHB, the color changes from yellow restore the fluorescence (Figure 4(C)).
to brown, which is derived from a ferric chloride reagent. How- A protocol of this sensor is listed below.
ever, this test lacks sensitivity as analysis of a series of GHB
amounts using Scott Kit demonstrates that concentration as high
as 300 mM GHB only gives a weak positive test, yet this amount Materials:
of GHB is enough to cause death. Normal GHB amounts within Green Date aqueous solution (50 μM), dichloromethane.
a cup of drink only give negative result with Scott Kit (Parsons, Protocol:
Harris, & Bravo, 2004). 1. Add 2 ml of dichloromethane to 2 ml GHB analyte
­solution.
2. Shake the mixture well.
A FLUORESCENT SENSOR FOR THE 3. Wait until two layers separate and collect the downside
PRODRUG OF GHB–GBL organic layer.
4. Dry the organic layer under reduced pressure.
GBL is a pharmacologically inactive compound. However, it is 5. After drying, add 100 μl Green Date solution and mix
easily metabolized to GHB in blood stream and stomach in the well.
presence of peripheral lactonases. Therefore, GHB and GBL 6. Visualize with green laser.
have similar psychopharmacological effects after ingestion. Due
to its wide usage and easy accessibility as an industrial solvent
and a chemical reagent, sexual predators have turned to GBL
as a result of the much more stringent regulations on GHB. CONCLUSION
Compared with GHB, GBL has higher bioavailability due to the
There is no doubt that the involvement of GHB and some other
fact that it is more lipophilic and can be absorbed through oral
date rape drugs in sexual assaults is becoming a serious social
administration more rapidly (Palatini et al., 1993). In view of
problem. Since their first introduction in 1960, GHB’s fate has
its adverse effects as a date rape drug, Zhai et al. (2013) devel-
been changed from a medicine that heals patients to a notori-
oped the first fluorescent sensor for GBL. Similar to the GHB
ous date rape drug that brings nothing more than pain and loss.
sensor, the researchers screened thousands of fluorescent dyes
Although the legal status of GHB has become harsher than before,
generated from a large variety of fluorescent scaffolds. The
it is still a popular date rape drug for sexual predators due to the
high-throughput screening followed an image-based process
easy availability of its precursors. Therefore, the necessity to
with the pictures of the fluorescent probes taken before and after
detect GHB in the body fluids of presumed victims and test kits
addition of GBL (Figure 4(D)). Researchers could then compare
that could conduct multisample field tests prior to ingestion has
the observed fluorescence intensities of the images and identify
dramatically increased. Over the past 20 years significant efforts
the probes that exhibit clear differences. With such a method,
have been made to develop useful tools for the practical and rapid
one compound named Green Date (Figure 4(A)) was selected
detection of GHB. However, the number of such tools is still lim-
as the final GBL fluorescent sensor. Upon excitation using
ited whereas their properties in terms of efficiency and selectivity
530 nm green light, Green Date emits an orange fluorescence
are not satisfying. We hope with this discussion of currently avail-
when interacting with GBL. Because the GBL detection limit of
able GHB detection methods, new sensing tools could be designed
Green Date (3 mg/ml) in water is above the allowed amount in
with improved methodology and performances. It should be noted
drinks (Figure 4(B)), an extraction method that can help remove
that such sensing tools cannot only help to prevent DFSA but will
the interfering components and preconcentrate GBL was devel-
also assist in understanding GHB-related neural activities.
oped by the researchers in order to construct a visual detection
kit of GBL. As a brief introduction, a certain amount of drink
samples was extracted with same volume of dichloromethane. APPLICATIONS TO OTHER ADDICTIONS
The organic layer was collected, dried, and resuspended in a
AND SUBSTANCE MISUSE
small portion of Green Date aqueous solution (50 μM) prepared
beforehand. After mixing, the fluorescence could be readily GHB and GBL are key CNS depressants that exist in almost all liv-
visualized with a green laser pointer. If samples do not contain ing bodies but their neural functions still remain blurred. Unravel-
GBL, green light can pass through the clear sample solution and ing these mysteries could help to understand the most fundamental
customers observe a green color; when the drink samples con- aspects of brain activity. On the other hand, optical methods pro-
tain GBL, orange fluorescence will be clearly seen and caution vide a feasible and convenient way to detect these species not only
has to be taken. within the range of cells and tissues but also in vivo. Thus optical
The mechanism of the interaction between GBL and Green detection of GHB and GBL should enlighten the biological studies
Date was further explored by dynamic light scattering and 19F of these neurodepressants. Furthermore, among the various neuro-
NMR experiments. It was proved that Green Date molecules logical species, GHB and GBL are especially difficult to design
stacked together and formed aggregates in aqueous solution sensors due to their simplified structure and lack of response sites.
to minimize contact with water, and hence their fluorescence However, with the help of a diversity-oriented fluorescent library
is diminished (aggregation caused quenching). With increas- approach, for the first time, researchers could successfully develop
ing amounts of GBL which is relatively more hydrophobic than fluorescent sensors for these species. It should encourage and
water molecules, they could enter the stacked aggregates of Green inspire the practitioners who are exploring this field.
534  PART | II  Club Drugs

FIGURE 4  Fluorescence detection of GBL using Green Date. (A) Structure of Green Date. (B) Fluorescent spectra of Green Date after incubation
with different concentrations of GBL (inner). Linear correlation of fold change in fluorescence versus concentration of GBL. (C) Schematic explanation
of the proposed mechanism of interaction between Green Date and GBL (star: Green Date molecule; black ball: GBL molecule). (D) Schematic work
flow of screening platform in GBL sensor development. Adapted with permission from Zhai et al. (2013). Copyright 2013, Royal Society of Chemistry.

DEFINITION OF TERMS Drug-facilitated sexual assault  Predatory rape is a sexual assault


on one person through the usage of date rape drugs or alcohols.
GHB  It is a very common natural substance existing in the CNS of Usually the victim is incapacitated by intentionally administered
almost all animals. It is also widely spread in wine, citrus fruits, drugs. Unlike physical violence or other rape, DFSA is a crime of
and beef. GHB is now most notorious as a date rape drug and is sexual entitlement.
currently strictly regulated in the USA, Canada, Australia and New
Zealand, and the majority of Europe. GHB functions through the
interaction with GHB receptor and induces nausea, dizziness, and KEY FACTS OF GHB AND GBL OPTICAL
unconsciousness.
GBL  It is a colorless liquid with hygroscopic properties. It is miscible
SENSORS
with water and naturally exists in wine as a result of processing, l 
Optical methods to detect date rape drugs have revealed not
though in very tiny amounts. In the human body, GBL reacts with lac- only social impacts but also biomedical implications.
tonase and forms GHB. Therefore, it is deemed as a prodrug of GHB. l DFSA is mostly likely to occur in bars or similar recreational
Colorimetric assay  In analytical chemistry, colorimetry is a technique places, where UV lamps are normally equipped for entertain-
to determine the amount of colored substances, and colorimetric ment purposes. Thus fluorescent probes for DFSA that can be
assays thus use the amount of colored substances to determine the excited by UV light should be conveniently applied in such
existence or amount of analytes. The assay method has evolved from places.
direct observation to absorbance measurement and now to extrac- l Fluorescent sensors for GHB is especially important to under-
tion of RGB values, which provides the option of high-throughput stand its neurological functions in living animals.
processing of multiple reactions. l Optical methods could potentially be a robust and noninvasive
Fluorescent sensor  Fluorescence indicates a process of electromag- bioimaging approach to study small molecule neurotransmitters.
netic wave absorption, relaxation, and longer wavelength light emis- l The first fluorescent sensors for GHB and GBL have proven
sion. Fluorescent sensors could exhibit emission change—either their application in various drinks.
intensity or wavelength—upon interaction with the analyte. This
approach usually provides high sensitivity and large response range.
Dynamic light scattering  It is a physical approach to determine the
SUMMARY POINTS
size distribution profile of particle suspension or polymer solutions.
Rayleigh scattering happens when a beam of light hits small parti- l This chapter summarizes all the available optical methods for
cles. By detecting the scattered photons and correlate their intensity sensing common date rape drugs including GHB and GBL.
fluctuations, knowledge of their size and amount could be calcu- l The detection of GHB and GBL and other date rape drugs is
lated and collected. sociologically and biologically crucial.
Assay Sensor for GHB Chapter | 49  535

l Optical detection, especially fluorescence sensing of GHB, is Mamelak, M. (1989). Gammahydroxybutyrate: an endogenous regulator
difficult due to its lack of responding site. of energy metabolism. Neuroscience Biobehavioral Reviews, 13(4),
l Supramolecular colorimetric assay provides a potential way 187–198.
to detect GHB, with the help of computer software to extract Mason, P. E., & Kerns, W. P., 2nd (2002). Gamma hydroxybutyric
RGB values. acid (GHB) intoxication. Academic Emergency Medicine, 9(7),
l The diversity-oriented fluorescent library approach is a highly 730–739.
feasible method to find fluorescent sensors for small molecule McCusker, R. R., Paget-Wilkes, H., Chronister, C. W., & Goldberger, B. A.
neurotransmitters and depressants. (1999). Analysis of gamma-hydroxybutyrate (GHB) in urine by gas
l The use of hydrogen bond and disaggregation-induced emis- chromatography-mass spectrometry. Journal of Analytical Toxicology,
sion could facilitate sensor discovery for GHB and GBL. 23(5), 301–305.
l Green Date and GHB Orange are both applicable to various Meyers, J. E., & Almirall, J. R. (2004). A study of the effectiveness of
drinks. The next step would be optimizing these sensors and commercially available drink test coasters for the detection of “date
developing them into product version. rape” drugs in beverages. Journal of Analytical Toxicology, 28(8),
685–688.
Nemeth, Z., Kun, B., & Demetrovics, Z. (2010). The involvement of
REFERENCES gamma-hydroxybutyrate in reported sexual assaults: a systematic
review. Journal of Psychopharmacology, 24(9), 1281–1287.
Baumes, L. A., Buaki Sogo, M., Montes-Navajas, P., Corma, A., & Garcia, Palatini, P., Tedeschi, L., Frison, G., Padrini, R., Zordan, R., Orlando, R., …
H. (2010). A colorimetric sensor array for the detection of the date- Ferrara, S. D. (1993). Dose-dependent absorption and elimination of
rape drug γ-hydroxybutyric acid (GHB): a supramolecular approach. gamma-hydroxybutyric acid in healthy volunteers. European Journal of
Chemistry-a European Journal, 16(15), 4489–4495. Clinical Pharmacology, 45(4), 353–356.
Bessman, S. P., & Fishbein, W. N. (1963). Gamma-hydroxybutyrate, a nor- Parsons, S. M., Harris, D. O., & Bravo, D. T. (2004). Methods, compo-
mal brain metabolite. Nature, 200, 1207–1208. sitions and apparatuses for detection of gamma-hydroxybutyric acid
Brailsford, A. D., Cowan, D. A., & Kicman, A. T. (2012). Pharmacokinetic (GHB). US Patent 6703216.
properties of γ-hydroxybutyrate (GHB) in whole blood, serum, and Quest, D. W., & Horsley, J. (2007). Field-test of a date-rape drug detection
urine. Journal of Analytical Toxicology, 36(2), 88–95. device. Journal of Analytical Toxicology, 31(6), 354–357.
Ciolino, L. A., Mesmer, M. Z., Satzger, R. D., Machal, A. C., McCauley, Ropero-Miller, J. D., & Goldberger, B. A. (1998). Recreational drugs.
H. A., & Mohrhaus, A. S. (2001). The chemical interconversion of Current trends in the 90s. Clinics in Laboratory Medicine, 18(4),
GHB and GBL: forensic issues and implications. Journal of Forensic 727–746.
Sciences, 46(6), 1315–1323. Shannon, M., & Quang, L. S. (2000). Gamma-hydroxybutyrate, gamma-
Couper, F. J., & Lorgan, B. K. (2004). Addicted to driving under the butyrolactone, and 1,4-butanediol: a case report and review of the lit-
influence-a GHB/GBL case report. Journal of Analytical Toxicology, erature. Pediatric Emergency Care, 16(6), 435–440.
28(6), 512–515. Sumnall, H. R., Woolfall, K., Edwards, S., Cole, J. C., & Beynon, C. M.
Galloway, G. P., Frederick, S. L., Staggers, F. E., Gonzales, M., Stalcup, (2008). Use, function, and subjective experiences of gamma-hydroxy-
S. A., & Smith, D. E. (1997). Gamma-hydroxybutyrate: an emerging drug butyrate (GHB). Drug Alcohol Dependence, 92(1–3), 286–290.
of abuse that causes physical dependence. Addiction, 92(1), 89–96. Zhai, D., Agrawalla, B. K., Eng, P. S., Lee, S. C., Xu, W., & Chang, Y. T.
Lesar, C. T., Decatur, J., Lukasiewicz, E., & Champeil, E. (2011). Report on (2013). Development of a fluorescent sensor for an illicit date rape
the analysis of common beverages spiked with gamma-hydroxybutyric drug-GBL. Chemical Communications, 49(55), 6170–6172.
acid (GHB) and gamma-butyrolactone (GBL) using NMR and the Zhai, D., Tan, Y. Q., Xu, W., & Chang, Y. T. (2014). Development of a
PURGE solvent-suppression technique. Forensic Science International, fluorescent sensor for an illicit date rape drug-GHB. Chemical Com-
212(1–3), e40–e45. munications, 50(22), 2904–2906.
Lettieri, L., & Fung, H. L. (1978). Improved pharmacological activity
via pro-drug modification: comparative pharmacokinetics of sodium
gamma-hydroxybutyrate and gamma-butyrolactone. Research Commu-
nications in Chemical Pathology and Pharmacology, 22(1), 107–118.

You might also like