ROAR Forensics

Geraldine, United Kingdom

ROAR Forensics

Geraldine, United Kingdom
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Halberstadt A.L.,University of California San DiegoCalifornia | Klein L.M.,University of California San DiegoCalifornia | Brandt S.D.,Liverpool John Moores University | Elliott S.P.,ROAR Forensics | Fiedler W.J.,Hurststrasse 6a
ACS Chemical Neuroscience | Year: 2015

A series of N-benzylated-5-methoxytryptamine analogues was prepared and investigated, with special emphasis on substituents in the meta position of the benzyl group. A parallel series of several N-benzylated analogues of 2,5-dimethoxy-4-iodophenethylamine (2C-I) also was included for comparison of the two major templates (i.e., tryptamine and phenethylamine). A broad affinity screen at serotonin receptors showed that most of the compounds had the highest affinity at the 5-HT2 family receptors. Substitution at the para position of the benzyl group resulted in reduced affinity, whereas substitution in either the ortho or the meta position enhanced affinity. In general, introduction of a large lipophilic group improved affinity, whereas functional activity often followed the opposite trend. Tests of the compounds for functional activity utilized intracellular Ca2+ mobilization. Function was measured at the human 5-HT2A, 5-HT2B, and 5-HT2C receptors, as well as at the rat 5-HT2A and 5-HT2C receptors. There was no general correlation between affinity and function. Several of the tryptamine congeners were very potent functionally (EC50 values from 7.6 to 63 nM), but most were partial agonists. Tests in the mouse head twitch assay revealed that many of the compounds induced the head twitch and that there was a significant correlation between this behavior and functional potency at the rat 5-HT2A receptor. © 2014 American Chemical Society.


Elliott S.P.,ROAR Forensics | Brandt S.D.,Liverpool John Moores University | Wallach J.,University of the Sciences in Philadelphia | Morris H.,The New School for Social Research | Kavanagh P.V.,St James Hospital
Journal of Analytical Toxicology | Year: 2015

2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as 'MXP' or '2-MeO-diphenidine' (or 2-MXP), has been available as a 'research chemical' since 2013 as a purported alternative to the 'dissociative anesthetics' methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urinewere encountered in forensic casework. The 2-, 3-and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework. © The Author 2015. Published by Oxford University Press.


Elliott S.P.,ROAR Forensics | Brandt S.D.,Liverpool John Moores University | Freeman S.,University of Manchester | Archer R.P.,States Analysts Laboratory
Drug Testing and Analysis | Year: 2013

5-(2-Aminopropyl)indole (5-IT) and 3-(2-aminopropyl)indole (α-methyltryptamine, AMT) are isomeric substances and their differentiation can be a challenge under routine analytical conditions, especially when reference material is unavailable. 5-IT represents a very recent addition to the battery of new psychoactive substances that are commercially available from online retailers. This report illustrates how subtle differences observed under mass spectral and UV conditions can help to facilitate the differentiation between the two isomers. Analyses included 1H and 13C NMR, GC-EI/CI ion trap MS, applications of several U/HPLC-DAD and HPLC-MS methods. Investigations currently underway also highlight the confirmation that AMT was detected in a number of fatal intoxications. These findings also demonstrate that there is a potential risk of misidentification when dealing with both substances. © 2012 John Wiley & Sons, Ltd..


PubMed | The New School for Social Research, University of the Sciences in Philadelphia, Liverpool John Moores University, Trinity College Dublin and 3 more.
Type: Journal Article | Journal: Drug testing and analysis | Year: 2016

The structurally diverse nature of the 1,2-diphenylethylamine template provides access to a range of substances for drug discovery work but some have attracted attention as research chemicals. The most recent examples include diphenidine, i.e. 1-(1,2-diphenylethyl)piperidine and 2-methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine (MXP, methoxyphenidine, 2-MXP) that have been associated with uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist activity. Analytical challenges encountered during chemical analysis include the presence of positional isomers. Three powdered samples suspected to contain 2-MXP were obtained from three Internet retailers in the United Kingdom and subjected to analytical characterization by gas chromatography (GC) and high performance liquid chromatography (HPLC) coupled to various forms of mass spectrometry (MS). Nuclear magnetic resonance spectroscopy, infrared spectroscopy and thin layer chromatography were also employed. This was supported by the synthesis of all three isomers (2-, 3- and 4-MXP) by two different synthetic routes. The analytical data obtained for the three purchased samples were consistent with the synthesized 2-MXP standard and the differentiation between the isomers was possible. Distinct stability differences were observed for all three isomers during in-source collision-induced dissociation of the protonated molecule when employing detection under HPLC selected-ion monitoring detection, which added to the ability to differentiate between them. Furthermore, the analysis of a 2-MXP tablet by matrix assisted inlet ionization Orbitrap mass spectrometry confirmed that it was possible to detect the protonated molecule of 2-MXP directly from the tablet surface following addition of 3-nitrobenzonitrile as the matrix.


PubMed | ROAR Forensics, St James Hospital, University of the Sciences in Philadelphia, Liverpool John Moores University and The New School for Social Research
Type: Case Reports | Journal: Journal of analytical toxicology | Year: 2015

2-Methoxydiphenidine, i.e. 1-[1-(2-methoxyphenyl)-2-phenylethyl]piperidine, also known as MXP or 2-MeO-diphenidine (or 2-MXP), has been available as a research chemical since 2013 as a purported alternative to the dissociative anesthetics methoxetamine and ketamine. Three deaths which involved the detection of 2-MXP in post-mortem blood and urine were encountered in forensic casework. The 2-, 3- and 4-methoxyphenyl positional isomers were synthesized to confirm the identity and concentration of 2-MXP. The 2-MXP femoral blood concentrations in the cases were found to be 24.0, 2.0 and 1.36 mg/L (the latter with an alternative cause of death). Some additional prescription drugs were encountered at therapeutic concentrations in all three cases. Analysis of the biofluids allowed the detection and characterization of various metabolites, including the suggested presence of hydroxy-2-MXP as the main metabolite with the hydroxyl group located on the piperidine rather than the phenyl or benzyl moiety. Additional metabolites included O-desmethyl-2-MXP and hydroxylated O-desmethyl-2-MXP. Diphenidine and hydroxy-diphenidine, also showing the presence of the hydroxyl group on the piperidine ring, were also detected. It was not possible to identify whether these arose from 2-MXP biotransformation or whether they represented the presence of diphenidine as a separate substance. These are the first published fatalities involving 2-MXP and presents analytical data to assist analytical toxicologists with future casework.


PubMed | Synex Ltd, State Bureau of Criminal Investigation Schleswig Holstein, University of the Sciences in Philadelphia, Liverpool John Moores University and 6 more.
Type: Journal Article | Journal: Drug testing and analysis | Year: 2016

Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N


Brandt S.D.,Liverpool John Moores University | Baumann M.H.,U.S. National Institute on Drug Abuse | Partilla J.S.,U.S. National Institute on Drug Abuse | Kavanagh P.V.,St James Hospital | And 12 more authors.
Drug Testing and Analysis | Year: 2014

During the second half of 2013, a total of 26 deaths involving para-methyl-4-methylaminorex (4,4'-DMAR) were reported to the European Monitoring Centre for Drugs and Drug Addiction. While aminorex and 4-methylaminorex (4-MAR) are known psychostimulants, nothing is known about the comparatively new para-methyl analog. Analytical characterization of two independent samples obtained from online vendors confirmed the presence of the (±)-cis isomer that also appeared to be associated with at least 18 of the 26 deaths. Extensive characterizations included crystal structure analysis, single, tandem, and high-resolution mass spectrometry, liquid and gas chromatography, and nuclear magnetic resonance spectroscopy. For the work described here, both the (±)-cis and (±)-trans racemates were also synthesized, confirming that the differentiation between these two forms was straight-forward. Monoamine transporter activity was studied using rat brain synaptosomes which included the comparison with d-amphetamine, aminorex and (±)-cis-4-MAR. (±)-cis-4,4'-DMAR was a potent, efficacious substrate-type releaser at transporters for dopamine, norepinephrine and serotonin with EC50 values of 8.6±1.1 nM (DAT), 26.9±5.9 nM (NET) and 18.5±2.8 nM (SERT), respectively. The potency of (±)-cis-4,4′-DMAR at DAT and NET rivalled that of other psychomotor stimulant drugs like d-amphetamine and aminorex. However, (±)-cis-4,4′-DMAR had much more potent actions at SERT and activity at SERT varied more than 100-fold across the four drugs. The potent releasing activity of (±)-cis-4,4′-DMAR at all three monoamine transporters predicts a potential for serious side-effects such as psychotic symptoms, agitation, hyperthermia and cardiovascular stimulation, especially after high-dose exposure or following combination with other psychostimulants. © 2014 John Wiley & Sons, Ltd.


PubMed | ROAR Forensics, Liverpool John Moores University, University of the Sciences in Philadelphia and St James Hospital
Type: Journal Article | Journal: Drug testing and analysis | Year: 2016

The rise in new psychoactive substances that are available as research chemicals (RCs) remains a significant forensic and legislative challenge. A number of arylcyclohexylamines have attracted attention as RCs and continue to be encountered, including 3-MeO-PCP, 3-MeO-PCE and 3-MeO-PCPr. These compounds are commonly perceived as ketamine-like dissociative substances and are believed to act predominantly via antagonism of the N-methyl-D-aspartate (NMDA) receptor. To aid in the identification of newly emerging substances of abuse, the current studies were performed. The syntheses of fifteen N-alkyl-arylcyclohexylamines are described. Analytical characterizations were performed via gas chromatography and high performance liquid chromatography coupled to multiple forms of mass spectrometry as well as nuclear magnetic resonance spectroscopy, ultraviolet diode array detection and infrared spectroscopy. The series consisted of the N-alkyl derivatives (N-methyl, N-ethyl, N-propyl) of phenyl-substituted and isomeric 2-, 3- and 4-methoxy phenylcyclohexylamines, as well as the N-alkyl derivatives obtained from 3-methylphenyl and 2-thienyl moieties. In addition to the presentation of a range of previously unreported data, it was also found that positional isomers of aryl methoxyl-substituted arylcyclohexylamines were readily distinguishable under a variety of analytical conditions. Copyright 2015 John Wiley & Sons, Ltd.


PubMed | State Bureau of Criminal Investigation Schleswig Holstein, University of the Sciences in Philadelphia, Liverpool John Moores University, ROAR Forensics and 3 more.
Type: Journal Article | Journal: Drug testing and analysis | Year: 2016

1-Propionyl-d-lysergic acid diethylamide hemitartrate (1P-LSD) has become available as a research chemical in the form of blotters and powdered material. This non-controlled derivative of d-lysergic acid diethylamide (LSD) has previously not been described in the published literature despite being closely related to 1-acetyl-LSD (ALD-52), which was developed in the 1950s. This study describes the characterization of 1P-LSD in comparison with LSD using various chromatographic and mass spectrometric methods, infrared and nuclear magnetic resonance spectroscopy. An important feature common to LSD and other serotonergic hallucinogens is that they produce 5-HT2A -receptor activation and induce the head-twitch response (HTR) in rats and mice. In order to assess whether 1P-LSD displays LSD-like properties and activates the 5-HT2A receptor, male C57BL/6J mice were injected with vehicle (saline) or 1P-LSD (0.025-0.8mg/kg, IP) and HTR assessed for 30min using magnetometer coil recordings. It was found that 1P-LSD produced a dose-dependent increase in HTR counts, and that it had ~38% (ED50 =349.6nmol/kg) of the potency of LSD (ED50 =132.8nmol/kg). Furthermore, HTR was abolished when 1P-LSD administration followed pretreatment with the selective 5-HT2A receptor antagonist M100907 (0.1mg/kg, SC), which was consistent with the concept that the behavioural response was mediated by activation of the 5-HT2A receptor. These results indicate that 1P-LSD produces LSD-like effects in mice, consistent with its classification as a serotonergic hallucinogen. Nevertheless, the extent to which 1P-LSD might show psychoactive effects in humans similar to LSD remains to be investigated. Copyright 2015 John Wiley & Sons, Ltd.


Elliott S.,ROAR Forensics | Smith C.,ROAR Forensics | Cassidy D.,ROAR Forensics
Forensic Science International | Year: 2010

A reduced blood pH (ketoacidosis) from the production of β-oxidative ketone bodies as a result of alcoholism (alcoholic ketoacidosis, AKA) or diabetes (diabetic ketoacidosis, DKA) can feature in many fatalities and analytical evidence can be used to support a pathological diagnosis, or provide a possible cause of death in the absence of other pathologically significant findings. Existing beliefs concerning the relationship of BHB concentrations, acetone and ethanol have been re-examined by analysis of BHB, acetone and ethanol in over 350 fatalities grouped into alcoholics, diabetics, alcoholic diabetics, coupled with speculative cases and those with an alternative cause of death. Uniquely, the concentrations of BHB were measured in post-mortem blood, urine and vitreous humour using selective GC-MS. The results showed that existing beliefs need to be re-evaluated. Ethanol is not always low (<10. mg/dL) or absent in cases of AKA. Also, the absence of acetone does not preclude a high BHB (>250. mg/L), therefore acetone can be used as an initial marker pathologically significant ketoacidosis. For blood and urine BHB concentrations the following interpretative ranges can be used (in mg/L); normal (<50. mg/L), raised (51-249. mg/L), high and pathologically significant (>250. mg/L). Initial data suggest vitreous humour BHB could be a useful alternative in the absence of blood (same interpretative ranges may also apply). Analytical recommendation for investigation of post-mortem ketoacidosis is also presented. © 2009.

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