PEER-REVIEWED ABSTRACT PRESENTED AT THE

2015 ANNUAL MEETING OF

THE INTERNATIONAL ASSOCIATION OF FORENSIC TOXICOLOGISTS

WOP13

ETHYLPHENIDATE IN POST MORTEM CASES Morley S.*, Smith P., Cole R., Hikin L. Forensic Toxicology Service ‐ University Hospital, Leicester, United Kingdom steve.r.morley@uhl‐tr.nhs.uk

Ethylphenidate is a product of pro‐drugs and . Ethylphenidate is a potent psychostimulant that acts as both a and reuptake inhibitor. Ethylphenidate may be formed when large quantities of ethanol and methylphenidate are co‐ ingested, via hepatic trans‐esterification or, as in these cases, is administered as a parent compound. Ethylphenidate was made a controlled substance in the UK in April 2015. The UK National Poisons Information Service has limited experience of reported exposures to ethylphenidate. These exposures have not been confirmed by laboratory analysis. Clinical features reported are consistent with those of . The onset of effects appears to be within 45 minutes of exposure with user‐reports suggesting the duration of action as 2 to 3 hours. There is a single peer‐reviewed case report that records death may have had some contribution from, but was unlikely to have been caused specifically, with an ethylphenidate in femoral blood at a concentration of 110ng/mL. To review the toxicological findings and circumstances of death in cases in which ethylphenidate was detected. All routine cases underwent ethanol quantitation by headspace GC‐FID, and screening/quantitation of matrices by LC‐MSMS. In the seven cases in which ethylphenidate was detected by screening, quantitation was performed by a validated LC‐MS/MS method using deuterated methylphenidate as an internal standard. Cause of death was obtained from pathologists report. Between February 2013 and January 2015 there were 7 cases in which ethylphenidate was detected. Methylphenidate and metabolite (ritalinic acid) were not detected in any of these cases (limit of detection 5ng/mL). Two cases had post mortem blood ethanol detected (30 and 74mg/100mL). Death in one case was concluded to have been due to ethylphenidate toxicity with a post mortem blood concentration of 2182 ng/mL. No other drugs were detected in this case. Two cases were concluded as having died from hanging. These had ethylphenidate concentrations of 1336 and 871 ng/mL. In these cases other drugs were present (ethanol, metabolites, , , dothiepin and ). The other 4 cases had ethylphenidate concentrations of 106, 136, 26 and 107 ng/mL and also included the presence of ethanol, , zopiclone, sertraline, aripiprazole, 2‐aminoindane, heroin metabolites, , cocaine metabolites, 5‐APB/6‐APB, diazepam and . Ethylphenidate toxicity is still an uncommon cause of death in the case mix of the Leicester forensic toxicology laboratory. There has only been a single case in which it was judged to be the primary cause of death, where the postmortem level was 2182 ng/mL. Comparison to the therapeutic levels of methylphenidate (up to 50ng/mL) and the previous published case report indicate that some of the concentrations detected in the other six cases may have led to toxic effects but there was either an alternative mechanism of death (such as hanging) or mixed drug toxicity. There were 2 cases in which ethanol was detected, but no methylphenidate, and no other markers of significant ethanol use, such as ethyl glucuronide, so although co‐administration of cannot be fully excluded, it is unlikely.

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