THE STREET-LIKE SYNTHESIS OF KROKODIL RESULTS IN THE FORMATION OF AN ENLARGED CLUSTER OF KNOWN AND NEW MORPHINANS WITH THERAPEUTIC POTENTIAL

José Soares, Emanuele Alves, André Silva, Natália Figueiredo, João F. Neves, Sara Cravo, Maria Rangel, Annibal Netto, Félix Carvalho, Ricardo Jorge Dinis-Oliveira, Carlos Afonso

Index: 10.1021/acs.chemrestox.7b00126

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Abstract

“Krokodil” is the street name for a homemade injectable drug that has been used as a cheap substitute for heroin. Codeine is the opioid starting material for krokodil synthesis and desomorphine is the opioid claimed to be the main component of krokodil and the main responsible for its addictive and psychoactive characteristics. However, due to its peculiar manufacture, using cheap raw materials, krokodil is composed by a large and complex mixture of different substances. In order to shed some light upon the chemical complexity of krokodil, its profiling was conducted by reverse phase high performance liquid chromatography coupled to photodiode array detector (RP-HPLC-DAD) and by liquid chromatography coupled to high resolution tandem mass spectrometry (LC-ESI-IT-Orbitrap-MS). Besides desomorphine, codeine and morphine, profiting from the high resolution mass spectrometry (HRMS) data, an endeavor to study the morphinans content in krokodil was set for the first time. Considering codeine as the only morphinan precursor and the possible chemical transformations that can occur during krokodil synthesis, the morphinan chemical space was designed and 95 compounds were defined. By making use of the morphinan chemical space in krokodil, the exact masses featured by HRMS, and the morphinan mass fragmentations patterns, a targeted identification approach was designed and implemented. The proposed 95 morphinans were searched using the full scan chromatogram of krokodil and findings were validated by mass fragmentation of the correspondent precursor ions (MS2 spectra). Following this effort, a total of 54 morphinans were detected, highlighting the fact that these additional morphinans may contribute to the psychotropic effects of krokodil.