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      Analysis of Synthetic Cathinones Commonly Found in Bath Salts in Human Performance and Postmortem Toxicology: Method Development, Drug Distribution and Interpretation of Results

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      Journal of Analytical Toxicology
      Oxford University Press (OUP)

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          Abstract

          To date, the Toxicology Section of the Montgomery County Coroner's Office/Miami Valley Regional Crime Laboratory has identified six synthetic cathinones, commonly found in bath salt products, in 43 cases. Thirty-two cases will be reviewed here, including all of the postmortem cases, all of the human performance cases that had blood specimens submitted, and one urine-only human performance case. The following compounds have been confirmed: 3,4-methylenedioxypyrovalerone (MDPV), 3,4-methylenedioxymethcathinone (methylone), pyrovalerone, pentylone, alpha-pyrrolidinopentiophenone (alpha-PVP) and methedrone. The method also screens for mephedrone, butylone and 3-fluoromethcathinone. Case demographics show 42 white males and females ranging in age from 19 to 53 years. The remaining case was that of a 34-year-old Hispanic male. The 43 cases represent 17 driving under the influence, two domestic violence, four suicides, 12 overdoses, six accidents, one drug-facilitated assault and one homicide. Data will be presented on the distribution of some of these cathinones in various matrices. After review, blood concentration does not appear to predict outcome regarding fatalities or impairment. The highest MDPV concentration occurred in a suicide by hanging and the highest methylone concentration was in a driver. The confirmation method is a liquid-liquid extraction with detection by liquid chromatography triple quadrupole mass spectrometry using electrospray ionization in multiple reaction monitoring mode.

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          The toxicology of bath salts: a review of synthetic cathinones.

          Synthetic cathinones have recently emerged and grown to be popular drugs of abuse. Their dramatic increase has resulted in part from sensationalized media attention as well as widespread availability on the Internet. They are often considered "legal highs" and sold as "bath salts" or "plant food" and labeled "not for human consumption" to circumvent drug abuse legislation. Cathinone is a naturally occurring beta-ketone amphetamine analogue found in the leaves of the Catha edulis plant. Synthetic cathinones are derivatives of this compound. Those that are being used as drugs of abuse include butylone, dimethylcathinone, ethcathinone, ethylone, 3- and 4-fluoromethcathinone, mephedrone, methedrone, methylenedioxypyrovalerone (MDPV), methylone, and pyrovalerone. Synthetic cathinones are phenylalkylamines derivatives, and are often termed "bk-amphetamines" for the beta-ketone moiety. They may possess both amphetamine-like properties and the ability to modulate serotonin, causing distinct psychoactive effects. Desired effects reported by users of synthetic cathinones include increased energy, empathy, openness, and increased libido. Cardiac, psychiatric, and neurological signs and symptoms are the most common adverse effects reported in synthetic cathinone users who require medical care. Deaths associated with use of these compounds have been reported. Exposure to and use of synthetic cathinones are becoming increasingly popular despite a lack of scientific research and understanding of the potential harms of these substances. The clinical similarities to amphetamines and MDMA specifically are predictable based on the chemical structure of this class of agents. More work is necessary to understand the mechanisms of action, toxicokinetics, toxicodynamics, metabolism, clinical and psychological effects as well as the potential for addiction and withdrawal of these agents.
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            Clinical experience with and analytical confirmation of "bath salts" and "legal highs" (synthetic cathinones) in the United States.

            Recently, there has been a worldwide rise in the popularity and abuse of synthetic cathinones. In 2009 and 2010, a significant rise in the abuse of a new group of synthetic cathinones was reported in Western Europe. In 2010, the rapid emergence of a new drug of abuse, referred to as bath salts or "legal high," occurred in the USA. The growing number of cases along with the alarming severity of the effects caused by the abuse of these substances prompted significant concern from both healthcare providers and legal authorities. We report the experience of the first 8 months of two regional poison centers after the emergence of a new group of substances of abuse. This was a retrospective case series of patients reported to two poison centers with exposures to bath salts. Additionally, 15 "product samples" were obtained and analyzed for drug content using GC/MS. There were 236 patients of which 184 (78%) were male. Age range was 16-64 years (mean 29 years, SD 9.4). All cases were intentional abuse. There were 37 separate "brand" names identified. Clinical effects were primarily neurological and cardiovascular and included: agitation (n = 194), combative behavior (n = 134), tachycardia (n = 132), hallucinations (n = 94), paranoia (n = 86), confusion (n = 83), chest pain (n = 40), myoclonus (n = 45), hypertension (n = 41), mydriasis (n = 31), CPK elevations (n = 22), hypokalemia (n = 10), and blurred vision (n = 7). Severe medical outcomes included death (n = 1), major (n = 8), and moderate (n = 130). Therapies included benzodiazepines (n = 125), antipsychotics (n = 47), and propofol (n = 10). Primary dispositions of patients were: 116 (49%) treated and released from ED, 50 (21%) admitted to critical care, 29 (12%) admitted to psych, and 28 (12%) lost to follow up. Nineteen patients had blood and/or urine analyzed using GC/MS. MDPV was detected in 13 of 17 live patients (range 24-241 ng/mL, mean 58 ng/mL). The four samples with no drug detected, reported last use of bath salts >20 h prior to presentation. Three of five patients had MDPV detected in urine (range 34-1386 ng/mL, mean 856 ng/mL). No mephedrone or methylone was detected in any sample. Quantitative analysis performed on postmortem samples detected MDPV in blood at 170 ng/mL and in urine at 1400 ng/mL. No other synthetic cathinones were detected. This is the first report of MDPV exposures with quantitative blood level confirmation. Clinical effects displayed a sympathomimetic syndrome, including psychotic episodes often requiring sedation, movement disorders, and tachycardia. Within 8 months of their appearance, 16 states had added synthetic cathinones to the controlled substances list as a Schedule I drug. We report the emergence of a new group of substances of abuse in the USA, known as bath salts, with quantitative results in 18 patients. State and federal authorities used timely information from poison centers on the bath salt outbreak during investigations to help track the extent of use and the effects occurring from these new drugs. Close collaboration between state authorities and poison centers enhanced a rapid response, including legislation.
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              Analyses of second-generation 'legal highs' in the UK: initial findings.

              In the UK, mephedrone and other so-called 'legal high' derivatives have recently been classified as Class B, Schedule I under the Misuse of Drugs Act 1971. Since then, alternative products have been advertised on a number of websites. In order to obtain an immediate snapshot of the situation, 24 products were purchased online from 18 UK-based websites over a period of 6 weeks following the ban in April 2010. Qualitative analyses were carried out by gas chromatography ion trap mass spectrometry using electron- and chemical ionization modes, nuclear magnetic resonance spectroscopy, and comparison with reference standards. Overall, the purchased products consisted of single cathinones or cathinone mixtures including mephedrone, butylone, 4-methyl-N-ethylcathinone, flephedrone (4-fluoromethcathinone) and MDPV (3,4-methylenedioxypyrovalerone), respectively. Benzocaine, caffeine, lidocaine, and procaine were also detected. The emphasis was placed on 'Energy 1' (NRG-1), a product advertised as a legal replacement for mephedrone-type derivatives usually claiming to contain naphyrone (naphthylpyrovalerone, O-2482). It was found that 70% of NRG-1 and NRG-2 products appeared to contain a mixture of cathinones banned in April 2010 and rebranded as 'new' legal highs, rather than legal chemicals such as naphyrone as claimed by the retailers. Only one out of 13 NRG-1 samples appeared to show analytical data consistent with naphyrone. These findings also suggest that both consumers and online sellers (unlike manufacturers and wholesalers) are, most likely unknowingly, confronted with the risk of criminalization and potential harm. Copyright © 2010 John Wiley & Sons, Ltd.
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                Author and article information

                Journal
                Journal of Analytical Toxicology
                Journal of Analytical Toxicology
                Oxford University Press (OUP)
                0146-4760
                1945-2403
                March 11 2013
                April 01 2013
                January 29 2013
                April 01 2013
                : 37
                : 3
                : 135-146
                Article
                10.1093/jat/bks136
                23361867
                2549f94e-69e8-4974-8234-753076847028
                © 2013
                History

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