Intriguing Cytotoxicity of the Street Dissociative Anesthetic Methoxphenidine: Unexpected Impurities Spotted
Bronislav Jurásek, Silvie Rimpelová, Martin Babor, Jan Čejka, Vilém Bartůněk, Martin Kuchař
International Journal of Molecular Sciences February 14, 2022 DOI: 10.3390/ijms23042083 via OpenAlex
Summary
A sample of the dissociative anesthetic methoxphenidine from the black market contained an unusual bromo- and chloro-zincate anion impurity. In vitro cytotoxicity tests on kidney, liver, and bladder cell lines showed that the street sample was markedly more toxic than a pure methoxphenidine standard, suggesting the impurity caused the increased toxicity. A method using X-ray powder diffraction (XRPD) was developed to identify such anions and distinguish different crystalline forms of methoxphenidine, providing additional data not captured by routine analysis.
Study at a glance
| Characteristics | In vitro study Peer reviewed |
|---|---|
| Population | Cell lines of kidney, liver, and bladder origin |
| Keywords | Cytotoxicity Impurity Dissociative Powder diffraction Toxicology |
| Citations | 7 |
| Key finding | Street methoxphenidine containing a bromo- and chloro-zincate anion impurity exhibited markedly higher cytotoxicity than the pure standard. |
Abstract
The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.