Cambridgeshire, United Kingdom
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McQuade D.,Guys and St Thomas NHS Foundation Trust | Hudson S.,HFL Sport Science | Dargan P.I.,Guys and St Thomas NHS Foundation Trust and Kings Health Partners | Dargan P.I.,King's College London | And 3 more authors.
European Journal of Clinical Pharmacology | Year: 2013

Purpose: There is increasing reported use of synthetic cannabinoid receptor agonists (SCRA) across Europe. To date, there is limited information on the acute toxicity (harm) related to the use of these products. We describe here a case in which an individual developed convulsions related to the use of the SCRA AM-2201. Case report: A 20 year old male smoked a "Spice" (SCRA-containing) product called "Black Mamba," and rapidly after smoking, he had a generalised self-terminating tonic-clonic convulsion. After a 2 h observation period in the Emergency Department (ED), he self-discharged against medical advice. Subsequent analysis of urine collected at the time of presentation to the ED detected metabolites of AM-2201; no other drugs were detected on extensive analytic screening. Discussion: This is the first case of convulsions related to the use of SCRA described in Europe, and the first case of convulsions related to the use the SCRA AM-2201 confirmed by analysis of biological samples. It is important for emergency physicians, clinical toxicologists and clinical pharmacologists managing those presenting with acute toxicity related to the use of SCRA to analytically confirm the exact compound(s) involved, to enable accurate description of the acute toxicity associated with individual SCRA. © 2012 Springer-Verlag.


Castle P.C.,University of Bedfordshire | Kularatne B.P.,Disability Target Shooting Great Britain | Brewer J.,University of Bedfordshire | Mauger A.R.,University of Kent | And 6 more authors.
European Journal of Applied Physiology | Year: 2013

Heat acclimation (HA) can improve thermoregulatory stability in able-bodied athletes in part by an enhanced sweat response. Athletes with spinal cord lesion are unable to sweat below the lesion and it is unknown if they can HA. Five paralympic shooting athletes with spinal cord lesion completed seven consecutive days HA in hot conditions (33.4 ± 0.6 C, 64.8 ± 3.7 %rh). Each HA session consisted of 20 min arm crank exercise at 50 % V̇O2peak followed by 40 min rest, or simulated shooting. Aural temperature (T aur) was recorded throughout. Body mass was assessed before and after each session and a sweat collection swab was fixed to T12 of the spine. Fingertip whole blood was sampled at rest on days 1 and 7 for estimation of the change in plasma volume. Resting T aur declined from 36.3 ± 0.2 C on day 1 to 36.0 ± 0.2 C by day 6 (P < 0.05). During the HA sessions mean, T aur declined from 37.2 ± 0.2 C on day 1, to 36.7 ± 0.3 C on day 7 (P < 0.05). Plasma volume increased from day 1 by 1.5 ± 0.6 % on day 7 (P < 0.05). No sweat secretion was detected or changes in body mass observed from any participant. Repeated hyperthermia combined with limited evaporative heat loss was sufficient to increase plasma volume, probably by alterations in fluid regulatory hormones. In conclusion, we found that although no sweat response was observed, athletes with spinal cord lesion could partially HA. © 2012 Springer-Verlag.


Scarth J.P.,HFL Sport Science | Clarke A.,HFL Sport Science | Teale P.,HFL Sport Science | Mill A.,UK Environment Agency | And 2 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

The use of steroids as growth-promoting agents in food production is banned under European Union legislation. Detecting the abuse of testosterone, nandrolone, boldenone, oestradiol and progesterone is complicated by the fact that these steroids are known to be endogenous in certain situations. In this study, the concentrations of characteristic metabolites of each of these steroids were quantified in populations of untreated steers and heifers. Steroid concentration population data were then used by a statistical model (the Chebyshev inequality) to produce threshold concentrations for screening and confirming the abuse of these steroids in steer and nonpregnant heifer urine. In addition to thresholds based on testing one animal (a '1 out of 1' approach), new methods based on testing multiple animals from a herd (a 'y out of n' approach) allowed threshold concentrations to be significantly reduced and hence false compliances to be minimised. In the majority of cases, the suggested thresholds were found to be capable of confirming the abuse of endogenous steroids in steers and heifers. In the case of oestradiol abuse in the female, however, confirmation based on a threshold is not possible and alternative methods such as gas chromatography-combustion-isotope ratio mass spectrometry are required. In addition to the steer and heifer populations, a small number of pregnant animals were also tested, yielding insights into the biosynthetic pathways of some of the steroids. © 2011 Taylor & Francis.


Stead S.L.,UK Environment Agency | Wolodko-Cierniak K.B.,UK Environment Agency | Richmond S.F.,UK Environment Agency | Sharman M.,UK Environment Agency | And 4 more authors.
Food Additives and Contaminants - Part A Chemistry, Analysis, Control, Exposure and Risk Assessment | Year: 2011

A potentiometric biosensor assay based on a commercially available polyclonal antibody was developed to detect tylosin residues in animal feed. The method can be used as a rapid (less than 45 min) laboratory-based procedure or as a portable field-test for the simultaneous measurement of up to 12 different samples. For both procedures the qualitative detection capability (CCβ) for tylosin was determined as 0.2 mgkg -1 in a range of animal feeds with a measurement repeatability at concentrations between 0.2 and 4mg kg -1 of ≤13% coefficient of variation (%CV). The field-test format was capable of detecting tylosin residues at operating (external air) temperatures ranging between +4 and 37°C, although some reduction in signal was observed at the lower temperatures. The laboratory-based tylosin assay was evaluated using 16 medicated and 22 non-medicated feeds and was found to give comparable data with a confirmatory method based upon liquid chromatography-tandem mass spectrometry (LC-MS/MS). The potential to develop a multi-probe format assay for the simultaneous detection of tylosin, spiramycin and virginiamycin was also demonstrated. Cross-validation in a second laboratory showed the assay to be transferable, reliable and robust. © 2011 Taylor & Francis.


Dargan P.I.,Guys and St Thomas NHS Foundation Trust and Kings Health Partners | Hudson S.,HFL Sport Science | Ramsey J.,St George's, University of London | Wood D.M.,Guys and St Thomas NHS Foundation Trust and Kings Health Partners
International Journal of Drug Policy | Year: 2011

Background: Spice is the iconic brand name of a smokeable herbal mixture containing synthetic cannabinoid receptor agonists. It has been available on the Internet/in head shops in Europe since at least 2006. The synthetic cannabinoid receptor agonist constituents of Spice were classified in the UK as Class B agents in December 2009. This study assessed the impact of this legislation on the synthetic cannabinoid receptor agonists present in Spice products and whether new synthetic cannabinoid receptor agonists outside of the legislation are now available. Methods: Spice products were bought, prior to and after the change in the UK legislation, from a range of Internet legal high websites selling to UK consumers. Products were analysed using liquid chromatography high-resolution tandem mass spectrometry (LCMSMS). Identification of the synthetic cannabinoid receptor agonist(s) detected was made by comparison to existing databases or by 'in silico' methods. Results: Sixteen products were purchased prior to the UK control of synthetic cannabinoid receptor agonists; all contained at least one synthetic cannabinoid receptor agonist. 20 products were purchased after the UK control; no active compounds were detected in 3 (15%). The remaining 17 (85%) all contained at least one classified synthetic cannabinoid receptor agonist. Additionally, 2 synthetic cannabinoid receptor agonists not covered under current UK generic legislation (AM-694 and the 'novel Belarus compound') were detected. Conclusion: Despite the UK 'Spice' classification, classified synthetic cannabinoid receptor agonists continue to be supplied over the Internet to UK users. Furthermore, new synthetic cannabinoid receptor agonists not covered by the legislation are appearing. Consideration needs to be given to reviewing the UK legislation so that suppliers cannot circumvent it by supplying legal alternatives to the classified synthetic cannabinoid receptor agonists. © 2011 Elsevier B.V.


Hudson S.,HFL Sport Science | Ramsey J.,St George's, University of London | King L.,Home Office Advisory Council on the Misuse of Drugs | Timbers S.,HFL Sport Science | And 3 more authors.
Journal of Analytical Toxicology | Year: 2010

A range of "Herbal High" products were tested for synthetic cannabinoids (cannabinomimetics) to qualitatively determine and compare their individual and relative content. Liquid chromatography-high resolution accurate mass spectrometry was used to rapidly screen samples for a range of cannabinomimetics using mono-isotopic masses derived from the elemental composition of target analytes. A screening database of over 140 compounds was rapidly created. This approach, combined with further tandem mass spectrometric experiments, also facilitated the detection and identification of compounds for which reference materials were not available. Previously reported cannabinomimetics, including JWH-018 and CP47,497 and its homologues, were detected in varying relative proportions along with several tentatively identified unreported cannabinomimetics. In some countries, the decision has been made to include these substances within their drug control legislation, and other countries are considering similar action. The currently applied drug screening techniques are unlikely to be effective in providing scientific evidence to support their identification in seized products. The application of high-resolution accurate mass spectrometry offers a solution. In addition, the technology provides a relatively simple and quick method for screening products, building substance databases, and even identifying novel substances using a combination of accurate mass derived elemental composition and fragment ions combined with fragmentation prediction software.


Gray B.P.,HFL Sport Science | Biddle S.,HFL Sport Science | Pearce C.M.,HFL Sport Science | Hillyer L.,British Horseracing Authority
Drug Testing and Analysis | Year: 2013

Fluticasone propionate (FP) is an anti-inflammatory agent with topical and inhaled applications commonly used in the treatment of asthma in steroid-dependent individuals. The drug is used in racehorses to treat Inflammatory Airway Disease; this work was performed in order to advise on its use and detect potential misuse close to racing. Methods were developed for the extraction and analysis of FP from horse plasma and a carboxylic acid metabolite (FP-17βCOOH) from horse urine. The methods utilize ultra high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in order to detect the extremely low concentrations of analyte present in both matrices. The developed methods were used to analyse plasma and urine samples collected following inhaled administration of FP to six thoroughbred horses. FP was detected in plasma for a minimum of 72h post-administration and FP-17βCOOH was detected in urine for approximately 18h post-administration. The results show that it is possible to detect FP in the horse following inhaled administration. © 2012 John Wiley & Sons, Ltd.


Clarke A.,HFL Sport Science | Scarth J.,HFL Sport Science | Teale P.,HFL Sport Science | Pearce C.,HFL Sport Science | Hillyer L.,British Horseracing Authority
Drug Testing and Analysis | Year: 2011

Detection of androgenic-anabolic steroid abuse in equine sports requires knowledge of the drug's metabolism in order to target appropriate metabolites, especially where urine is the matrix of choice. Studying 'designer' steroid metabolism is problematic since it is difficult to obtain ethical approval for in vivo metabolism studies due to a lack of toxicological data. In this study, the equine in vitro metabolism of eight steroids available for purchase on the Internet is reported; including androsta-1,4,6-triene-3,17-dione, 4-chloro,17α-methyl-androsta-1,4-diene-3,17β-diol, estra-4,9-diene-3,17-dione, 4-hydroxyandrostenedione, 20-hydroxyecdysone, 11-keto-androstenedione, 17α-methyldrostanolone, and tetrahydrogestrinone. In order to allow for retrospective analysis of sample testing data, the use of a high-resolution (HR) accurate-mass Thermo LTQ-Orbitrap liquid chromatography-mass spectrometry (LC-MS) instrument was employed for metabolite identification of underivatized sample extracts. The full scan LC-HRMS Orbitrap data were complimented by LC-HRMS/MS and gas-chromatography-mass spectrometry (GC-MS) experiments in order to provide fragmentation information and to ascertain whether GC-MS was capable of detecting any metabolite not detected by LC-HRMS. With the exception of 20-hydroxyecdysone, all compounds were found to be metabolized by equine liver S9 and/or microsomes. With the exception of 17α-methyldrostanolone, which produced metabolites that could only be detected by GC-MS, the metabolites of all other compounds could be identified using LC-HRMS, thus allowing retrospective analysis of previously acquired full-scan data resulting from routine equine drug testing screens. In summary, while in vitro techniques do not serve as a replacement for more definitive in vivo studies in all situations, their use does offer an alternative in situations where it would not be ethical to administer untested drugs to animals. Results of in vitro experiments to demonstrate the metabolism in the equine of 8 designer steroids found on the internet are presented. The use of high-resolution accurate-mass LC-MS along with in vitro methods provide a means of detailing the metabolism of designer steroids which have not been clinically tested and therefore prove to be difficult to obtain ethical approval for in vivo metabolism studies. Copyright © 2011 John Wiley & Sons, Ltd.


Teale P.,HFL Sport Science | Houghton E.,HFL Sport Science
Bioanalysis | Year: 2010

The fight against doping in sport using analytical chemistry is a mature area with a history of approximately 100 years in horseracing. In common with human sport, anabolic/androgenic steroids (AASs) are an important group of potential doping agents. Particular issues with their detection are extensive metabolism including both phase I and phase II. A number of the common AASs are also endogenous to the equine. A further issue is the large number of synthetic steroids produced as pharmaceutical products or as 'designer' drugs intended to avoid detection or for the human supplement market. An understanding of the metabolism of AASs is vital to the development of effective detection methods for equine sport. The aim of this paper is to review current knowledge of the metabolism of appropriate steroids, the current approaches to their detection in equine sport and future trends that may affect equine dope testing. © 2010 Future Science Ltd.


Houghton E.,HFL Sport Science | Maynard S.,HFL Sport Science
Handbook of Experimental Pharmacology | Year: 2010

This chapter reviews drug and medication control in equestrian sports and addresses the rules of racing, the technological advances that have been made in drug detection and the importance of metabolism studies in the development of effective drug surveillance programmes. Typical approaches to screening and confirmatory analysis are discussed, as are the quality processes that underpin these procedures. The chapter also addresses four specific topics relevant to equestrian sports: substances controlled by threshold values, the approach adopted recently by European racing authorities to control some therapeutic substances, anabolic steroids in the horse and LC-MS analysis in drug testing in animal sports and metabolism studies. The purpose of discussing these specific topics is to emphasise the importance of research and development and collaboration to further global harmonisation and the development and support of international rules. © 2009 Springer-Verlag Berlin Heidelberg.

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