A Fatality Due To Injection of Tiletamine and Zolazepam*

Abstract

A 22-year-old male with more than 28 needle marks on his right arm was found dead. First, he was suspected as a drug abuser. Blood, urine, spleen, and injection-site tissue was collected during autopsy. The blood and urine specimens were screened for drugs. Immunoassay studies did not show any illegal drugs. However, two unidentified peaks were isolated in both of these biological fluids by routine gas chromatography-flame-ionization detection (GC-FID) and thermionic specific detection. Additional gas chromatography-mass spectrometry analysis determined these two peaks to be tiletamine and zolazepam. These two agents are used in combination as veterinary anesthesia. The concentrations of these drugs in blood were quantitated by GC-FID and found to be 0.85 mg/L of tiletamine and 3.3 mg/L of zolazepam. In urine, tiletamine and its metabolite, 2-(ethylamino)-2-(2-thionyl) cyclohexanol, were identified to be present along with zolazepam. The concentrations of tiletamine and zolazepam in spleen were revealed to be 0.92 and 3.5 mg/kg, respectively. Injection-site tissue concentrations were determined to be 25.1 mg/kg tiletamine and 23.3 mg/kg for zolazepam. The cause of death in this case was determined to be due to the multiple drug intoxication of tiletamine and zolazepam.

Determination of constituents of Telazol®—tiletamine and zolazepam by a gas chromatography/mass spectrometry-based method

“…However, the details of extraction methodology and validation parameters were unclear from their report. Two methods employing GC/MS instrumentation have also been reported [10,11]. Chung et al [10] extracted tiletamine and zolazepam from 1 ml of alkalinized blood with 5 ml of ethyl acetate three times, back-extracted the pooled ethyl acetate into acid, and reextracted the acidic solution twice with 5 ml of ethyl acetate.…”

“…Two methods employing GC/MS instrumentation have also been reported [10,11]. Chung et al [10] extracted tiletamine and zolazepam from 1 ml of alkalinized blood with 5 ml of ethyl acetate three times, back-extracted the pooled ethyl acetate into acid, and reextracted the acidic solution twice with 5 ml of ethyl acetate. This publication was a case report on a death related to abuse of Telazol ® and the authors did not perform a formal validation of the assay procedure.…”

“…Therefore, elucidation of pharmacokinetics of tiletamine and zolazepam is important to better understand the variability in the effects of Telazol ® . Previously reported assay methods for tiletamine and zolazepam include high-performance liquid chromatography coupled with UV detection [8,9] and GC/MS [10,11]. These methods have been published as part of either pharmacokinetic or toxicological investigations without formal validation of procedures.…”

A survey of the use of veterinary anesthetics in Korea

“…These anesthetics are not only traded on the illicit market under different names, but are also openly sold without restrictions to the public in some drugstores. Current conditions could be the cause of the resulting misuse and abuse of veterinary anesthetics, as well as possible socio-economic losses [3]. The main goals of the survey were to determine the actual state of animal anesthetic drug use, and to inform the public on survey responses from veterinarians and researchers in Korea.…”

Pre-exposure to ethanol, but not to caffeine and nicotine, induced place preference and self-administration of the NMDA receptor antagonist-benzodiazepine combination, Zoletil®

“…Abuse or misuse of Zoletil®, a veterinary anesthetic combination (1:1) of the N-methyl-D-aspartate (NDMA) receptor antagonist, tiletamine, and the benzodiazepine, zolazepam, has been reported in several studies (Chung et al, 2000;Cording et al, 1999;Kim, 2011;Lee et al, 2009;Quail et al, 2001;Redmond and Herman, 2002). In previous studies, we have demonstrated that this combination is rewarding and reinforcing in rats, but these effects were only manifested in animals repeatedly preexposed to Zoletil® or to other pharmacologically-related psychoactive drugs.…”