title: First detection of ethylphenidate in human fatalities after ethylphenidate intake.
abstract: Methylphenidate, a psychostimulant drug from the group of amphetamines is, among others, established in the treatment of attention deficit hyperactivity disorder and narcolepsy. It is also known to have a certain potential of abuse. In combination with alcohol, the metabolite ethylphenidate was detected in human plasma in small amounts. However, ethylphenidate is sold as "research chemical" via the Internet. It was put under German narcotics law in July 2013. In a recent case, where a deceased person was found in his apartment, the police seized a plastic bag with the inscription "ethylphenidate". An autopsy of the 32-year-old man yielded a mitral valve endocarditis, which must have persisted a while before death, in combination with a pneumonia. At the Forensic Toxicological Centre (FTC) in Munich femoral blood, liver, pericardium fluid, urine, stomach content and hair of the deceased were analyzed for ethylphenidate after sample preparation by an LC-Triple TOF 5600. Calibration curves were spiked with a methanolic 1mg/mL solution of ethylphenidate (substance provided by the State Office of Criminal Investigation in Munich) in whole blood in comparison to liver and femoral blood, in serum in comparison to pericardium fluid and in urine in comparison to urine and stomach content, respectively. Ethylphenidate was detected in all analyzed matrices. The spectrums of the human specimen were compared to those obtained from the calibration curves and identified as ethylphenidate. The measured concentrations were for femoral blood 110ng/mL, for liver 180ng/g, for pericardium fluid 131ng/mL, for urine 987ng/mL and for stomach content 20.7ng/mL, respectively. The stomach contained 200mL of a brownish-coloured liquid, resulting in a total amount of 4000ng ethylphenidate. The lowest calibrator for whole blood and serum was 1ng/mL and for urine 10ng/mL. As far as it is known to the authors, these are the first ethylphenidate levels measured in a case of ethylphenidate intake. Therefore these results can only be compared to methylphenidate concentrations with therapeutic levels ranging from 5 to 60ng/mL in serum. As the toxic levels for methylphenidate start from approximately 500ng/mL serum, we estimate that ethylphenidate in the concentrations mentioned above is not in a directly lethal range. But it has to be considered, that amphetamine-like drugs as methylphenidate are known for their cardiovascular side effects (like tachycardia and arrhythmia) and might therefore have contributed to death, which was attributed to endocarditis in combination with pneumonia.
authors.affiliation: Institute of Forensic Medicine, Ludwig Maximilians University, Munich, Germany; Forensic Toxicological Centre, Munich, Germany. Electronic address: j.krueger@ftc-muenchen.de.
authors.forename: J
authors.initials: J
authors.lastname: Krueger
authors.affiliation: Forensic Toxicological Centre, Munich, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Sachs
authors.affiliation: Forensic Toxicological Centre, Munich, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Musshoff
authors.affiliation: Forensic Toxicological Centre, Munich, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Dame
authors.affiliation: Bavarian State Criminal Police Office, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Schaeper
authors.affiliation: Institute of Forensic Medicine, Ludwig Maximilians University, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schwerer
authors.affiliation: Institute of Forensic Medicine, Ludwig Maximilians University, Munich, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Graw
authors.affiliation: Institute of Forensic Medicine, Ludwig Maximilians University, Munich, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Roider
mesh_terms: D000328:Adult; D000697:Central Nervous System Stimulants / Q000032:analysis*; D004696:Endocarditis / Q000473:pathology; D005766:Gastrointestinal Contents / Q000737:chemistry; D006197:Hair / Q000737:chemistry; D006801:Humans; D008099:Liver / Q000737:chemistry; D008297:Male; D008774:Methylphenidate / Q000031:analogs & derivatives* / Q000032:analysis; D010496:Pericardium / Q000737:chemistry; D011014:Pneumonia / Q000473:pathology
chemical_list: D000697:Central Nervous System Stimulants; D008774:Methylphenidate; C042400:ethylphenidate
keywords: Ethylphenidate; LC-Triple TOF; Methylphenidate; Postmortem toxicology; Ritalinic acid