Determination of new psychoactive substances in complex matrices by using methods based on micro-analytical systems

Notwithstanding the remarkable amplification of the network of controls, finalized to reduce the worldwide spread of illicit drug compounds, the abuse of psychotropic substances continues to be a rising phenomenon. The seizures of cocaine, heroin and illicit morphine and cannabis showed a constant trend from 2003 to 2012. The seizures of amphetamine-type stimulant followed the same trend until to 2010, while from 2010 to 2012 the seizures were trebled. In addition, some laboratories base their activity on developing of New Psychoactive Substances (NPSs) that fall outside international drug control convention. According to the United Nations Office on Drugs and Crime (UNODC), NPSs are defined as “substances of abuse…that are not controlled by the 1961 Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances…. In this context, the term ‘new’ does not necessarily refer to new inventions but to substances that have recently become available”. The spreading of uncommon psychotropic compounds is already a matter to take account. The number of NPSs on the global market more than doubled over the period 2009-2013 1. In recent years the detection of illicit drugs has been directed toward a rapid and accurate recognition analytical methods. The dramatic growth of the technology allows performing of analytical measurements employing volume in the range of the nanoliter and picoliter. This research project seeks to demonstrate the reliability of microfluidic systems, as analytical tools for forensic toxicological purposes. Several microfluidic devices can be used to pursue different aims; in the present project will be exposed three different strategies finalized to detect new psychoactive substances. Here, the term new, is utilized to indicate the voluptuary use of a medicine commonly administered for anesthetic aims, the ketamine, and the reveler utilization of an antitussive compound which is used in many over-the-counter drug, the dextromethorphan. The first strategy was focused on the developing of a set of paper microfluidic colorimetric tests for the analysis of ketamine and other common drugs of abuse. A variety of presumptive methods have been developed, including spot tests, chemical microscopy, TLC, GC and IR but many of these tests require skilled handlers, or like spot tests are incapable of simultaneously determining a wide variety of compounds in a single tube analysis step. To the best of our knowledge this work presents a unique process for running multiple assays simultaneously. The test can detect a wide variety of analytes using few micrograms of sample. Semiquantitative analysis is also possible using a smartphone and simple software. The proposed method doesn’t require highly qualified persons or expensive instrumentation, and it can be performed on-site enabling a prompt analytical response during police actions, border services, and airport security. The second part of the project emphasized the development and validation of a simple chiral separation method to identify and quantify the enantiomers of methorphan, and their main metabolites, by using cyclodextrin-assisted capillary zone electrophoresis (CD-CZE). To the best of our knowledge, the available methods are based on complex method cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) 2 or methods which require expensive chromatographic columns 3. In 2013, Koo C et al. developed a GC/MS by using achiral column, but the method was not applied to blood samples 4. The proposed method allowed to resolve dextromethorphan from levomethorphan in seizures of heroin and to perform the chiral identification and the quantification of methorphan enantiomers and their main metabolites, dextrorphan and levorphanol, in post-mortem blood, with an acceptable sensitivity. The final section of the project was centered on preliminary study finalized to the development of a method to detect ketamine, based on molecularly imprinted polymer-assisted capillary zone electrophoresis (MIP-CZE). The preliminary results were obtained by using the technology HPLC-MS to characterize the capacity of interaction in terms of extraction recovery of ketamine and common drugs of abuse non-structure related to ketamine. The tediousness of the process addressed us to develop an alternative rapid method able to evaluate the capacity of interaction of the molecularly imprinted polymers to use in CZE analysis. Preliminary results demonstrated the suitability and the reliability of the capillary electrophoresis to characterize the binding properties of molecularly imprinted polymers nanoparticle format (NP MIP). This study lays the groundwork for the possibility to utilize NP MIP as high-specificity selector to use in CZE analysis.