Emergence of new psychoactive substance 2-fluorodeschloroketamine: Toxicology and urinary analysis in a cluster of patients exposed to ketamine and multiple analogues.

New psychoactive substances (NPS) emerge continually, amongst which is a growing class of ketamine analogues with an arylcyclohexylamine backbone. Recently we reported a poisoning outbreak associated with 2-oxo-PCE (deschloro-N-ethyl-ketamine). The present report describes the emergence of another ketamine analogue, 2-fluorodeschloroketamine (2F-DCK). The compound was first detected in a patient's urine, its identity confirmed by accurate mass analysis and comparison with reference standard. Four putative metabolites were identified, including nor-2F-DCK, dehydronor-2F-DCK (major metabolite) and two hydroxylated derivatives of nor-2F-DCK. Between January and July 2019, 20 cases of analytically confirmed 2F-DCK exposure were encountered. In 19 out of 20 cases, at least one more ketamine-type drug was detected concurrently with 2F-DCK, including ketamine (90%), deschloroketamine (DCK, 50%), 2-oxo-PCE (45%) and tiletamine (10%). In particular, six of the cases showed the presence of 4 ketamine-type drugs in the same urine sample. The clinical effects observed in patients exposed to 2F-DCK are predominantly neurological (impaired consciousness, agitation, abnormal behaviour) and cardiovascular (hypertension, tachycardia); five patients had loss of consciousness or convulsion. Management was mainly supportive; all patients recovered uneventfully. This is the first clinical case series involving 2F-DCK and frontline medical personnel are urged to be aware of this rapidly expanding class of NPS, in particular the co-ingestion of multiple ketamine analogues.

A comprehensive and sensitive method for hair analysis in drug-facilitated crimes and incorporation of zolazepam and tiletamine into hair after a single exposure.

Hair is a highly relevant specimen that is used to verify drug exposure in victims of drug-facilitated crime (DFC) cases. In the present study, a new analytical method involving ultrahigh-performance liquid chromatography-tandem mass spectrometry was developed for determining the presence of model drugs, including zolazepam and tiletamine and their metabolites in hair specimens from DFCs. The incorporation of zolazepam and tiletamine into hair after a single exposure was investigated in Long-Evans rats with the ratio of the hair concentration to the area under the curve. For rapid and simple sample preparation, methanol extraction and protein precipitation were performed for hair and plasma, respectively. No interference was observed in drug-free hair or plasma, except for hair-derived diphenhydramine in blank hair. The coefficients of variance of the matrix effects were below 12%, and the recoveries of the analytes exceeded 70% in all of the matrices. The precision and accuracy results were satisfactory. The limits of quantification ranged from 20 to 50 pg in 10 mg of hair. The drug incorporation rates were 0.03 ± 0.01% for zolazepam and 2.09 ± 0.51% for tiletamine in pigmented hair. We applied the present method to real hair samples in order to determine the drug that was used in seven cases. These results suggest that this comprehensive and sensitive hair analysis method can successfully verify a drug after a single exposure in crimes and can be applied in forensic and clinical toxicology laboratories.

Simultaneous determination of zolazepam and tiletamine in dog plasma by liquid chromatography coupled to a tandem mass spectrometry.

A mixture of tiletamine, a dissociative anesthetic, and zolazepam, a minor tranquilizer, has been widely used as an anesthetic or an immobilizing agent in a variety of animal species. However, interestingly, their pharmacokinetic behaviors have been published only in polar bears and pigs. In this study, we introduce a sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for determining the two drugs in dog plasma. After simple protein precipitation with acetonitrile including midazolam (internal standard), the analytes were chromatographed on a reversed-phase column with a mobile phase of 10 m m ammonium acetate aqueous solution and acetonitrile (1:4, v/v). The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of zolazepam and tiletamine in plasma after a single intramuscular 10 mg dose of each in beagle dogs.

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

Tiletamine and zolazepam injection (Telazol) is used in veterinary surgical practice to induce short-term anesthesia and also to immobilize wild animals. The present work describes a sensitive method to measure tiletamine and zolazepam concentrations in plasma by means of GC/EI-MS on a 5% phenyl/95% methylpolysiloxane column. A simple liquid extraction procedure with ethyl acetate was used to isolate the two compounds and the same were separated and analyzed by GC/MS without derivatization. A formal validation of the assay demonstrated good accuracy and precision for both tiletamine (98-100.8%; C.V.total < 6.7%) and zolazepam (98.3-103.4; C.V.total < 13.2%). With 500 microl of plasma, the limits of quantification for both tiletamine and zolazepam were found to be 10 ng/ml. Both compounds were stable after three freeze-thaw cycles. The assay was used to analyze plasma samples collected from a pig after intramuscular administration of 10 mg/kg of Telazol. The plasma concentration-time profile of tiletamine and zolazepam from this representative pig is also provided.