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

Montgomery County Coroner's Office (MCCO)/Miami Valley Regional Crime Laboratory (MVRCL), Dayton, Ohio.
Journal of analytical toxicology (Impact Factor: 2.63). 01/2013; 37(3). DOI: 10.1093/jat/bks136
Source: PubMed

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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    • "All these cathinones are characterized by a pyrrolidine ring structure, making them different structurally and possibly also pharmacologically from other synthetic cathinones (Marusich et al., 2014; Simmler et al., 2013). Among the pyrovalerone cathinones, MDPV is currently the most widely detected and used, both in the EU (European Monitoring Center for Drugs and Drug Addiction, 2014b; Helander et al., 2014; Zuba and Byrska, 2013) and US (Leffler et al., 2014; Marinetti and Antonides, 2013; Spiller et al., 2011). In fact, MDPV has become the most frequently detected and used of all cathinones ( " bath salts " ) in some EU countries (Helander et al., 2014; Zuba and Byrska, 2013) and the US (Leffler et al., 2014). "
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    ABSTRACT: The pharmacology of novel psychoactive substances is mostly unknown. We evaluated the transporter and receptor interaction profiles of a series of para-(4)-substituted amphetamines and pyrovalerone cathinones. We tested the potency of these compounds to inhibit the norepinephrine (NE), dopamine (DA), and serotonin (5-HT) transporters (NET, DAT, and SERT, respectively) using human embryonic kidney 293 cells that express the respective human transporters. We also tested the substance-induced efflux of NE, DA, and 5-HT from monoamine-loaded cells, binding affinities to monoamine receptors, and 5-HT2B receptor activation. Para-(4)-substituted amphetamines, including 4-methylmethcathinone (mephedrone), 4-ethylmethcathinone, 4-fluoroamphetamine, 4-fluoromethamphetamine, 4-fluoromethcatinone (flephedrone), and 4-bromomethcathinone, were relatively more serotonergic (lower DAT:SERT ratio) compared with their analogs amphetamine, methamphetamine, and methcathinone. The 4-methyl, 4-ethyl, and 4-bromo groups resulted in enhanced serotonergic properties compared with the 4-fluoro group. The para-substituted amphetamines released NE and DA. 4-Fluoramphetamine, 4-flouromethamphetamine, 4-methylmethcathinone, and 4-ethylmethcathinone also released 5-HT similarly to 3,4-methylenedioxymethamphetamine. The pyrovalerone cathinones 3,4-methylenedioxypyrovalerone, pyrovalerone, α-pyrrolidinovalerophenone, 3,4-methylenedioxy-α-pyrrolidinopropiophenone, and 3,4-methylenedioxy-α-pyrrolidinobutiophenone potently inhibited the NET and DAT but not the SERT. Naphyrone was the only pyrovalerone that also inhibited the SERT. The pyrovalerone cathinones did not release monoamines. Most of the para-substituted amphetamines exhibited affinity for the 5-HT2A receptor but no relevant activation of the 5-HT2B receptor. All of the cathinones exhibited reduced trace amine-associated receptor 1 binding compared with the non-β-keto-amphetamines. In conclusion, para-substituted amphetamines exhibited enhanced direct and indirect serotonergic agonist properties and are likely associated with more MDMA-like effects. The pharmacological profile of the pyrovalerone cathinones predicts pronounced stimulant effects and high abuse liability.
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    • "Chemical analyses of numerous bath salts products have identified that the main active ingredients are usually analogues of the amphetaminelike stimulant cathinone (National Drug Intelligence Center, 2011). The presence of synthetic cathinone analogues was confirmed by toxicology screening and post mortem analysis of patients who had presented with bath salts intoxication (Coppola & Mondola, 2012; Marinetti & Antonides, 2013). Synthetic cathinone analogues first started to appear in Japan, Australia, and several European countries as early as 2006 and in the United States in 2009 (Camilleri et al., 2010; Bronstein et al., 2011; Gunderson et al., 2013; Zawilska & Wojcieszak, 2013). "
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    • "Severe cases of acute toxicity and fatalities have been reported (Maskell et al. 2001; Gustavsson & Escher 2009; Torrance & Cooper 2010; Wood et al. 2010a; 2010b; Lusthof et al. 2011; Wong & Holt 2011; Wood et al. 2011), but in many cases the presence of multiple drugs of abuse contributed to greater monoamine toxicity (Maskell et al. 2011; Coppola & Mondola 2012; Aromatario et al. 2012; Schifano et al. 2012; Prosser & Nelson 2012). Bizarre at-risk behaviors, such as hangings, stabbings, and self-mutilation, have also been reported amongst synthetic cathinone users (Schifano et al. 2012; Marinetti & Antonides 2013). Despite these incurred user consequences, use of synthetic cathinones is increasingly embedded in contemporary drug culture, whether through blending in existing street-available drugs such as MDMA and cocaine, or through chemical restructuring of compounds (Van Hout & Brennan 2011a; 2010b; 2012). "
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