Identification of Novel Psychoactive Substances Using Hyphenated Mass Spectrometric Techniques

Mar 01, 2012

The abuse of novel psychoactive substances (NPS) has been increasing over the last few years especially as these products have become so readily available through the Internet. These products are emerging mostly as analogues or precursors of well-known drugs of abuse, such as amphetamine. However, a major problem that is more complicated than their abusive potential is that these products may not contain what is on the label. In fact, they have been shown to contain a mixture of drugs and excipients that may be toxic or even lethal. The number of deaths caused by NPS products has been increasing over the last year. This increase stimulates the need for sensitive techniques to identify these substances and detect any organic impurity in their products. Hyphenated mass spectrometric techniques, such as gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS) offer some advantages. These techniques can both separate the constituents as well as confirm the chemical identity of the individual constituents in the product.

Novel psychoactive substances (NPS), also called "legal highs," represent a major threat to society, particularly to the younger generation. The threat caused by these drugs ranges from chronic psychological or physical illnesses to death. These drugs emerge as analogues or precursors of well-known drugs of abuse to bypass regulations, and the popularity of abusing them is increasing worldwide (1–4). The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) witnessed the emergence of 41 NPS in 2010, which was high compared to 24 substances in 2009 and 13 substances in 2008 (1). This was the largest number of substances reportedly introduced in a single year and included the following derivatives: 15 cathinones, 11 cannabinoids, a synthetic derivative of the plant based substance arecoline, five phenethylamines, one tryptamine, one piperazine, one cocaine, one ketamine, one phencyclidine, one aminoindan, one benzofuran, one aliphatic amine, and a substance that was described as designer medicine (1). The largest threat of these drugs is "amphetamine type" stimulants whose use, according to the United Nations report, has exceeded that of heroin and cocaine (3).

Several factors contribute to the emergence of these new drug derivatives, such as the drop in the purity of ecstasy, heroin, and cocaine over the last few years (3); the change in the sociological and behavioral context (5); the change in the drug phenomena from life-threatening treatment to lifestyle drugs; and the emergence of unregulated Internet websites. These drugs are marketed in an attractive way and can be found under the names "Legal," "Speed," "Research Chemical," "Plant Food," "Bath Salts," and "Not for human consumption" (6–8). They also are sold at a cheap price. A survey by Schmidt and colleagues showed that an average price of a designer drug in the UK was 9.69 GBP (9). In addition, a survey conducted by Carhart-Harris and colleagues showed that the popularity of common NPS was related to their legal status (2,10). The issue associated with the emergence of NPS is not simply related to increased use, but in the chemical diversity of the products available (1). The EMCDDA warns that the situation could become even more complex if the future witnesses a growing trend in the synthesis of new illicit drugs based on pharmaceutical products (1).

The toxicity and death case reports caused by these drugs have been increasing over the last few years (1,2,11). According to the United States Poison Control Center, 2237 calls were received from January to May 2011 relating to "bath salts" from 47 states; whereas, the number of calls in 2010 relating to these drugs was 303 (3,12). The cases from the last few years include paranoia and psychotic illnesses (13), acute liver failure (14,15), myocardial inflammation (16), acute sympathomimetic toxicity, hallucinations (1,17–24), and even death (1,20,25–29). The toxic effects associated with these products are not only related to the NPS pharmacological effect and dose, but also to the impurities and adulterants found in them. Often, these products do not only contain what is stated on the product label, or "label claim," but also contain a mixture of drugs and impurities. These additional substances are both deliberate (for example, to counteract a side effect) and accidental (such as, resulting from a poor quality synthesis). They range from organic to inorganic materials and include illicit drugs, pharmaceutical active ingredients, chemical precursors, and common excipients (30). For instance, analysis of products from patients admitted to the emergency department showed that out of 33 products analyzed 19% of nonliquid samples did not contain any drug and 23% contained a pharmaceutical active ingredient (31). The remaining samples contained both classic and novel recreational drugs, including methamphetamine, ketamine, chlorophenylpiperazine, and 1-benzylpiperazine. This highlights a significant issue of confirming the identity of these substances and ultimately the quantity in which they are present in a product.

Hyphenated mass spectrometric techniques, such as gas chromatography–mass spectrometry (GC–MS) and liquid chromatography–mass spectrometry (LC–MS), offer the advantage of selectivity and sensitivity for the analysis of NPS. These techniques can separate and potentially identify NPS of similar chemical structure, in contrast to rapid colorimetric tests that are often unable to discriminate between chemical analogues and isomers. The objective of this review is to highlight the MS methods used in the literature to date for the analysis of NPS. The review focuses on NPS products purchased from the Internet as well as product seizures. Most of the references in the literature cited the use of GC–MS; whereas only one reference utilized the application of LC–MS.

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