Synthesis and GC–MS analysis of a series of homologs and regioisomers of 3,4-methylenedioxypyrovalerone (MDPV) Younis F. Hamad Abiedalla a , Karim Abdel-Hay a,b , Jack DeRuiter a , C. Randall Clark a, * a Department of Pharmacal Sciences, Harrison School of Pharmacy, Auburn University, Auburn, AL 36849, USA b Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt 1. Introduction A number of synthetic cathinones (aminoketones, ‘‘bath salts’’) have appeared on the illicit drug market in recent years and these compounds represent a new emphasis in the development of designer drugs [1–5]. Derivatives identified in clandestine samples to date include a number of aromatic aminoketones such as MDPV (3,4-methylenedioxypyrovalerone), mephedrone, N-methylcathinone (also known as methcathinone or cat), 4- fluoromethcathinone (also known as flephedrone or 4-FMC) and 3,4-methylenedioxy-N-methylcathinone (also known as methy- lone, MDMC, bk-MDMA, or M1) [1]. These drugs are also structurally related to several schedule IV and V prescription drugs including bupropion (Zyban 1 , Wellbutrin 1 ), diethylpro- pion (Tenuate 1 ) and pyrovalerone (Centroton 1 ). Synthetic cathinones are typically marketed as ‘‘bath salts’’ as well as plant food/fertilizer, insect repellant, pond cleaner, vacuum fresheners and ‘‘plant food’’ and are sold under various names (Ivory Wave, Blizzard, etc.) in most areas of the United States [2]. MDPV is a so-called ‘‘designer drug’’ with stimulant effects similar to cocaine and amphetamine [5]. It is an analogue of pyrovalerone, a psychostimulant that was considered the first commercially available drug from the alpha-pyrrolidinophenone drug class which was synthesized and introduced to the market in the 1960s [6]. This stimulant was used to treat lethargy and chronic fatigue in the 1970s, but was later withdrawn from the market because of problems with abuse and dependency [7]. MDPV structurally resembles cathinone, found in Khat, and has thus been referred to as a synthetic cathinone derivative [8]. Acute toxicity of MDPV causes neurological, cardiovascular and psychopathological symptoms such as tachycardia, chest pain, dizziness, hypertension, hyperthermia, tremors, psychomotor agitation, hallucinations and depression [9,10]. The amphetamine-like effects of these synthetic cathinones appear to be a result of the release of norepinephrine, serotonin and dopamine as well as the inhibition of their reuptake [3,4]. Recently, a GC–MS method was described for the quantitative determination of MDPV in the urine of opioid-dependent patients [11]. Westphal et al. confirmed the structure of MDPV in a seized sample in Germany in 2007 using product ion mass spectrometry as well as with 1 H and 13 C NMR [12]. Westphal et al. [13] recently reported the infrared spectroscopic, nuclear magnetic resonance and mass spectrometric data for the designer drug 3,4-methyle- nedioxypyrrolidinobutyrophenone (MDPBP), a homolog of 3,4- methylenedioxy-pyrovalerone (MDPV). MDPBP was first seized in Germany in the year 2009. The structure elucidation of the aliphatic part of MDPBP was carried out by product ion spectrometry of the immonium ion at m/z = 112 formed after Forensic Science International 223 (2012) 189–197 A R T I C L E I N F O Article history: Received 3 July 2012 Received in revised form 20 August 2012 Accepted 22 August 2012 Available online 17 September 2012 Keywords: MDPV Cathinones Homologs Regioisomers GC–MS A B S T R A C T A series of ten homologous and regioisomeric aminoketones related to the designer synthetic cathinone derivative MDPV were evaluated in this study. These compounds were prepared from a common precursor chemical, piperonal (3,4-methylenedioxybenzaldehyde). These aminoketones show major peaks in their mass spectra corresponding to the regioisomeric and homologous immonium cation fragments from the loss of the methylenedioxybenzoyl radical species. All ten compounds in this study show equivalent EI MS fragments for the 3,4-methylenedioxybenzoyl fragments (m/z 149) and the methylenedioxybenzene fragment at m/z 121. The m/z 149 results from ionization of the carbonyl oxygen followed by an alpha-cleavage fragmentation. The loss of CO from this ion yields the m/z 121 fragments common to all spectra. The regioisomeric aminoketones yield equivalent mass spectra including mass equivalent regioisomeric immonium cation base peaks. A subset of these compounds has the same molecular weight and almost identical mass spectra to that of the designer drug MDPV. An evaluation of the effects of homologation on gas chromatographic retention showed that addition of a methylene (CH 2 ) in the nitrogen-containing ring increases retention more than the equivalent group added to the alkyl side-chain. ß 2012 Elsevier Ireland Ltd. All rights reserved. * Corresponding author. Tel.: +1 334 844 8326. E-mail address: clarkcr@auburn.edu (C.R. Clark). Contents lists available at SciVerse ScienceDirect Forensic Science International jou r nal h o mep age: w ww.els evier .co m/lo c ate/fo r sc iin t 0379-0738/$ – see front matter ß 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.forsciint.2012.08.040