Great Malvern, United Kingdom
Great Malvern, United Kingdom

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Corkery J.M.,St George's, University of London | Corkery J.M.,University of Hertfordshire | Elliott S.,Roar Forensics Ltd. | Schifano F.,St George's, University of London | And 3 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2012

2-DPMP (desoxypipradrol, 2-benzhydrylpiperidine, 2-phenylmethylpiperidine) and D2PM (diphenyl-2-pyrrolidin-2-yl-methanol, diphenylprolinol) are psychoactive substances, sold primarily over the Internet and in 'head' shops as 'legal highs', 'research chemicals' or 'plant food'. Originally developed in the 1950s for the treatment of narcolepsy and ADHD, 2-DPMP's use soon became very limited. Recreational use of 2-DPMP and D2PM appears to have started in March 2007, but only developed slowly. However, in the UK their popularity grew in 2009, increasing rapidly during summer 2010. At this time, there were many presentations to UK Emergency Departments by patients complaining of undesirable physical and psychiatric effects after taking 2-DPMP. In spring 2011 there were similar presentations for D2PM. Recreational use of these drugs has been reported only occasionally in on-line user fora. There is little scientifically-based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of these drugs. Here we describe what is known about them, especially on their toxicity, including what we believe to be the first three deaths involving the use of 2-DPMP in August 2010. There are no international controls imposed on 2-DPMP or D2PM. However, a ban on their UK importation was imposed in November 2011 and they became Class C drugs on 13 June 2012. It is critical that any other cases, including non-fatal overdoses, are documented so that a scientific evidence-base can be established for them. © 2012 Elsevier Inc.


Corkery J.M.,St George's, University of London | Corkery J.M.,University of Hertfordshire | Durkin E.,Roar Forensics Ltd | Elliott S.,Roar Forensics Ltd | And 3 more authors.
Progress in Neuro-Psychopharmacology and Biological Psychiatry | Year: 2012

5-MeO-DALT (N,N-diallyl-5-methoxytryptamine) is a psychoactive substance, sold primarily over the Internet as a 'research chemical' or 'plant food'. Although details for the synthesis of this tryptamine have been available since 2004, its use as a hallucinogenic drug has been reported only occasionally in on-line user fora. It is controlled in only a few countries world-wide. There is little scientifically-based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of 5-MeO-DALT. Here we review what is known about these aspects. We also report what we believe to be the first death involving the use of this substance. The case involved a man in his mid-20s who died in mid-2010. The coroner concluded that the deceased "died from injuries sustained after being hit by a lorry whilst under the influence of 5-MeODALT". It is critical that any other cases, including non-fatal instances, are documented so that a scientific evidence-base can be established for this drug. © 2012 Elsevier Inc.


Corkery J.M.,St George's, University of London | Corkery J.M.,University of Hertfordshire | Elliott S.,ROAR Forensics Ltd | Schifano F.,St George's, University of London | And 3 more authors.
Human Psychopharmacology | Year: 2013

Objectives: MDAI (5,6-methylenedioxy-2-aminoindane; 6,7-dihydro-5H- cyclopenta[f][1,3]benzodioxol-6-amine; 'sparkle'; 'mindy') is a psychoactive substance, sold primarily over the Internet and in 'head' shops as a 'legal high'. Synthesised and used as a research chemical in the 1990s, MDAI has structural similarities to MDMA (3,4-methylenedioxy-N-methylamphetamine) and shares its behavioural properties. Recreational use of MDAI appears to have started in Europe around 2007, with a noticeable increase after 2009 in the UK and other countries. Calls to National Poisons Information Services started in 2010, although there were few presentations to emergency departments by patients complaining of undesirable physical and psychiatric effects after taking MDAI. Recreational use of this drug has been reported only occasionally by online user fora. There is little scientifically based literature on the pharmacological, physiological, psychopharmacological, toxicological and epidemiological characteristics of this drug. Methods: Recent literature (including 'grey') was searched to update what is known about MDAI, especially on its toxicity. Results: The resultant information is presente1d, including on the first three UK deaths involving MDAI use in 2011 and 2012. 'Serotonin syndrome' appears to be a possible factor in these fatalities. Conclusion: It is vital that any other cases, including non-fatal overdoses, are documented so that a scientific evidence base can be established for them. Copyright © 2013 John Wiley & Sons, Ltd.


Parkin M.C.,King's College London | Longmoore A.M.,King's College London | Turfus S.C.,King's College London | Braithwaite R.A.,King's College London | And 3 more authors.
Journal of Chromatography A | Year: 2013

Targeting metabolites incorporated into hair following drug administration is useful for evidential purposes as this approach can aid in differentiating between administration and passive exposure. Greater analytical sensitivity is required than for targeting the parent drug alone. A 20. μm i.d. fused silica capillary column with an integrated electrospray emitter fritted with a single porous 10. μm polymeric bead has been successfully fabricated to facilitate this purpose. The sensitivity gains through the use of these integrated single fritted columns coupled to a nanoelectrospray source (nanoflow-LC nanoESI) over conventional liquid chromatography-tandem mass spectrometry (LC-MS/MS) columns was explored by their application to the detection of ketamine and its phase I metabolites in human hair. Hair was collected from 4 volunteers following the administration of a small oral dose of ketamine (50. mg) and subsequently analysed by the capillary-LC nanoESI approach. The drug and its metabolites were extracted from hair using solid phase extraction following a methanolic wash, pulverisation with a ball mill and acid digestion. From a 50. μL extract, 1. μL was injected and the method provided a limit of detection estimated to be 5. fg on column for ketamine and norketamine and 10. fg for dehydronorketamine. The single porous frit minimises extra column band broadening and offers an alternative fritting approach which reduces the blocking of the electrospray emitter, in comparison with other approaches such as sintering and polymerisation. © 2012 Elsevier B.V.


Soh Y.N.A.,King's College London | Elliott S.,ROAR Forensics Ltd
Drug Testing and Analysis | Year: 2014

The evolving nature of new psychoactive substances (NPS) - often referred to as 'legal highs', 'designer drugs' or 'bath salts' - presents an evolving challenge for toxicologists. Apart from the detection and identification of these compounds, further analytical challenges may arise from the presence of possible metabolites or degradation products which may have to be considered when devising an analytical strategy. Whilst there has been some stability research for some more established drugs of abuse and medicinal products, data on emerging NPS are less abundant. In order to address this need, 13 NPS (4-MEC, MDAI, methoxetamine, 5-MeO-DALT, 6-APB, MPA, 5-IAI, MDAT, 2-AI, AMT, 25C-NBOMe, AH-7921, 5-MAPB) were spiked in blood and plasma and kept at room temperature (20-23°C). Detection and identification of the suspected breakdown products were carried out by high performance liquid chromatography with diode-array detection (HPLC-DAD), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and ultra high performance liquid chromatography with high mass accuracy quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). 4-MEC became undetectable in blood within 14days with a corresponding loss of 54% in plasma. A breakdown product was identified as dihydro-4-MEC which was also found in vivo in a case work sample. Storage of AMT led to a range of potential breakdown products which were also found in vivo. The remaining substances were found to be stable for at least 21days in blood and plasma. This is the first time stability data have been published for these emerging substances and showed that additional compounds found during forensic casework were potential metabolites rather than instability products. In particular, presumptive metabolites of 25C-NBOMe and AH-7921 are presented. © 2013 John Wiley & Sons, Ltd.


Danenberg E.,World Health Organization | Sorge L.A.,University of Minnesota | Wieniawski W.,World Health Organization | Elliott S.,ROAR Forensics Ltd | And 2 more authors.
Drug and Alcohol Dependence | Year: 2013

Background: The WHO Executive Board revised the guidance that governs the procedures for the WHO review of psychoactive substances for international drug control in 2010. To meet the standards defined in these guidelines, the current evaluation methodology at WHO must be an evidence-based assessment. Methods: We describe the history of substance evaluation from 1912 to the present and the development of the evaluation methods over time including a description of the current assessment system, using reports from WHO and its predecessor, the League of Nations. Furthermore, we describe the current review system. Results: We found that some substances under international control were never reviewed; other substances were reviewed decades ago. Conclusions: We argue that assessments do not have unlimited validity, and therefore, substances need to be re-assessed periodically, as already recommended by the Expert Committee on Drug Dependence in 1982. We propose that the evaluation time be shortened; that the influence of the route of administration and/or dosage form of the preparation is considered in the evaluation; and we recommend studying national and regional assessment systems and adopting their best practices. With this article, we make a case for the inclusion of systematic review and other methods of comprehensive analysis of substance evaluation to arrive at a process of equal rigour and quality as already applied by WHO for the development of treatment guidelines. © 2013 World Health Organization.


Kintz P.,Laboratoire ChemTox | Evans J.,ROAR Forensics Ltd | Villain M.,Laboratoire ChemTox | Cirimele V.,Laboratoire ChemTox
Forensic Science International | Year: 2010

Methadone is not licensed for use in children though it can be employed for the management of neonatal opiate withdrawal syndrome. During the last 2 years, our laboratory has been asked to test for methadone and EDDP, its major metabolite, in hair from children that were admitted to hospital unconscious and where methadone had already been identified in a body fluid (4 cases) or where the children were deceased and evidence of methadone overdosage having already been established (2 cases). In all of these cases, segmental analysis revealed approximately the same amount of drug along the hair lock. As a consequence, contamination was considered as an issue and interpretation of the results was a challenge that deserves particular attention. After decontamination with dichloromethane and segmentation the hair was cut into small pieces, incubated overnight at 40 °C, liquid-liquid extracted and analysed with LC-MS/MS, using 2 transitions per compound. The LOQ for both methadone and EDDP was 10 pg/mg. In the first series involving children admitted to hospital, the following results were obtained:•case 1: 4 × 1 cm section, methadone at 0.05-0.08 ng/mg, no EDDP detected,•case 2: 4 × 1 cm section, methadone at 0.13-0.15 ng/mg, EDDP at 0.02 ng/mg,•case 3: 3 × 1.5 cm section, methadone at 0.07-0.09 ng/mg, EDDP at 0.01-0.03 ng/mg,•case 4: 6 × 2 cm section, methadone at 0.06-0.13 ng/mg, EDDP at 0.02-0.03 ng/mg. The following concentrations were obtained from the children who had died following a methadone overdose:•case 5: 2 × 2 cm section, methadone at 0.53-0.58 ng/mg, no EDDP detected,•case 6: 4 × 1 cm section, methadone at 0.44-0.77 ng/mg, EDDP at 0.04-0.06 ng/mg. The first observation is that all these concentrations are low by comparison with those observed in adults on methadone maintenance therapy. However, the more surprising observation is the relative homogenous concentrations along the hair locks in each specific case. This raises concerns around the possibility that contamination could have occurred prior to sampling and makes it hard to reach a conclusion regarding the possibility of repeated methadone exposure in the months prior the incidents. In these cases it was impossible to conclude that the children were deliberately administered methadone. The results of the analysis of hair could indicate that they were in an environment where methadone was being used and where the drug was not being handled and stored with appropriate care. The homogenous concentrations found on segmental analyses could be indicative of external contamination that may have arisen not only from direct contamination with the drug but also via contamination with body fluids at the post mortem or from sweat produced close to the time of the incident. In view of these results we concluded that a single determination should not be used firmly to discriminate long-term exposure to a drug. © 2009 Elsevier Ireland Ltd. All rights reserved.


Elliott S.,ROAR Forensics Ltd
Drug Testing and Analysis | Year: 2011

Although many piperazine derivatives exist, only a limited number have been studied, whereby they have been found to be generally stimulant in nature resulting from dopaminergic, noradrenergic, and predominantly serotoninergic effects in the brain. Reported toxic effects include agitation, anxiety, cardiac symptoms (e.g. tachycardia) and sometimes seizures. As for many drugs, they are primarily metabolized by cytochrome P450 with subsequent possible glucuronidation and/or sulfation. Their abuse has been relatively recently observed in the last decade with only a few identified in biological fluid (primarily 1-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (3-TFMPP)) despite publications of a number of analytical methods. Even when detected, however, the toxicological significance of their presence is often difficult to ascertain as many cases involve other drugs as well as a wide and overlapping range of concentrations found in blood (both in life and after death). This paper reviews the current pharmacological and toxicological information for piperazine derivatives and also includes new ante-mortem and post-mortem blood data. © 2011 John Wiley & Sons, Ltd.


Lim A.Y.,Nanyang Technological University | Seviour J.,Roar Forensics Ltd
Analytical Methods | Year: 2012

A detailed study on terbinafine excretion in latent fingerprints of a patient prescribed with the medication was carried out for a period of 14 days. Latent fingerprints collected from the patient were dusted with a fingerprint developing agent consisting of magnetized carbon black doped silica nanoparticles and directly analyzed by surface assisted laser desorption ionization-time of flight-mass spectrometry (SALDI-TOF-MS). MS and MSMS spectra of the latent fingerprints confirmed the presence of terbinafine, with the parent ion at m/z 292 and the fragment ion at m/z 141. Coupled with imaging, a gradual increment in the amount of terbinafine detected on the latent fingerprints from day 0 to day 14 was observed. When compared against commonly used 2,5-dihydroxybenzoic acid (DHB), these nanoparticles were more effective as a matrix for MS analysis of terbinafine, recording improved signal-to-noise values. The results demonstrate the efficacy of this technique for the detection of exogenous pharmaceutical drugs in latent fingerprints, providing information pertaining to the donor which may prove useful in cases of smudged prints. © 2012 The Royal Society of Chemistry.


Elliott S.,ROAR Forensics Ltd | Evans J.,ROAR Forensics Ltd
Forensic Science International | Year: 2014

Following the initial popularity of mephedrone (4-methylmethcathinone) there has been a stream of new "recreational drugs" entering the global market. The lack of clinical studies on the effects and toxicity of these drugs has made interpretation of toxicological findings difficult. In an attempt to assist in a better understanding of the extent of their use and the fatalities that have been linked to these compounds we present our collated findings in post-mortem and criminal casework where these have been detected and/or implicated. Between January 2010 and December 2012 we have detected new psychoactive substances (NPS) in 203 cases, with 120 cases in 2012 alone. The drugs detected in in life or post-mortem blood and urine are, in order of decreasing frequency; mephedrone, 4-methylethcathinone, BZP, MDPV, TFMPP, methoxetamine, 4-fluoromethcathinone, 4-methylamphetamine, PMA, methylone, PMMA, naphyrone, alpha-methyltryptamine, butylone, MDAI, desoxypipradrol, D2PM, MPA, synthetic cannabinoids, 2-AI, 5-IAI, 5-MeODALT, MDPBP, 5/6-APB, pentedrone and pentylone. Other drugs or alcohol were detected in 84% of the cases including other NPS and in fatalities it should be noted that alternative causes of death (including mechanical suicide, accidental death and non-psychoactive drug overdose) accounted for the majority. Related to this was that of all fatalities involving cathinones, 41% of these were hangings or other mechanical suicides, this was a higher proportion than seen with other drugs found in such cases. The presence of multiple NPS and/or other stimulants was a particular feature in various cases, however, of the drug deaths only 7% solely involved NPS. Across all case types and including some cases investigated in 2013, NPS concentrations showed a wide range but these and selected cases are presented to assist toxicological interpretation in future cases. © 2014 Elsevier Ireland Ltd.

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