DOI:10.1002/open.201800034 Chromogenic and Fluorogenic Probes for the Detection of Illicit Drugs Eva Garrido+,[a] Luis Pla+,[a] Beatriz Lozano-Torres,[a] Sameh El Sayed,[a, b] RamónMartínez-MµÇez,*[a, b, c] and FØlix Sancenón[a, b, c] ChemistryOpen 2018, 7,401 –428 401 2018 The Authors. PublishedbyWiley-VCH Verlag GmbH &Co. KGaA, Weinheim The consumption of illicit drugs has increased exponentially in sary to develop highly rapid, easy,sensitive,and selective recent years and has become aproblem that worries both methods for their detection. Currently,the most widely used governments and international institutions. The rapid emer- methods for drug detection are based on techniques that re- gence of new compounds, their easy access,the low levels at quire large measurement times, the use of sophisticated equip- which these substances are able to produce an effect, and ment, and qualified personnel. Chromo-and fluorogenic meth- their short time of permanence in the organism makeitneces- ods are an alternative to those classical procedures. 1. Introduction euro), ecstasy(22 million euro), opiates (18 millioneuro), and cocaine(17 million euro). According to their pharmacologic be- The use of novel illicit drugs and the constant appearance of havior,drugs can be divided into depressants, stimulants, hal- new psychoactive substances have rapidlygrown in the last lucinogenic, and opioids. years, and reports of the availability and manufacture of such Because of their harmfulnesstohealth,the ability to detect substances have increased.[1] Illicit drugs are those for which and quantify “drugsofabuse” in afast, easy,and reliable way nonmedicaluse has been prohibited by internationalcontrol is crucial. The United Nations Office on Drugs and Crime treaties because theyare believed to presentunacceptable (UNODC)established 28 million years of healthylife lost world- risks of addiction to users. According to the FDA, these com- wide in 2015 because of premature death and disability pounds can also be defined as “drugsofabuse”, substances caused by drug use.[3] Apart from the health problemsgenerat- that are used in amanner or amount inconsistentwith the le- ed by illicit drug consumption, UNODC exposes the existence gitimate medicaluse.[2] The problematic use of these illicit of continue evolvingorganized crime/terrorism related with drugs is associated with considerable mortality and morbidity. drug market. The European homologue,European Monitoring During the last 30 years, international control has been extend- Centrefor Drugs and Drug Addiction (EMCDDA), assumes ed from plant-based drugs (e.g. heroin, cocaine, and cannabis) there exists an important internet market dedicated to the sale to synthetic drugs (e.g. amphetamines,3,4-methylenedioxyme- of illicit substancesprotected by anonymization services.[4] Last thamphetamine, etc.) and pharmaceutical drugs (e.g. bupre- annualinforms of both the UNODCSand EMCDDAemphasized norphine, methadone, benzodiazepines, etc.). Specifically,syn- the necessity to control the production and distribution of thetic drugs are proliferating at an unprecedented rate and are new psychoactive substances(NPSs), as there are no assuran- posing significant public health challenges. The majority of ces to the consumers of the compounds contained,and the these addictive substances, directly or indirectly,attack the need to reinforce the development of new detection systems brain’s rewardsystem, mainly serotonin and dopamine recep- with the aim to decrease and eliminate the abuse of traditional tors, which regulate movement,emotion, motivation, and, and synthetic emerging drugs.[5] The development of reliable above all, the feelings of pleasure and euphoria associated methodsfor their detection and quantification is timely and ur- with the consumption of narcotics. Nowadays, amidst all illicit/ gently required. abuse substances,cannabis is the most consumed drug world- Nowadays, illicit drug detection is performed mostly through wide with 183 millioneuro incautions, followed by ampheta- chromatographic techniques, as can be seen by the large mines and derivatives (37 million euro), opioids (35 million number of research articles published in this field, because of the excellent features of chromatographictechniques, which [6] [a] E. Garrido,+ L. Pla,+ B. Lozano-Torres,Dr. S. El Sayed, include great versatility,robustness, and sensibility. Several [7] [8] [9] Prof. R. Martínez-MµÇez,Dr. F. Sancenón electrochemical, infrared, Raman spectroscopy, and mag- Instituto Interuniversitario de InvestigacióndeReconocimientoMolecular y netic resonance[1] methods also exist for the detection of sever- Desarrollo Tecnológico (IDM), Universitat Politcnica de Valncia al drugs, and these techniques show excellent results in terms Universitat de Valncia, Camí de Vera s/n,46022 Valncia (Spain) E-mail:[email protected] of selectivity and sensibility.However,they presentsome short- [b] Dr.S.ElSayed, Prof. R. Martínez-MµÇez,Dr. F. Sancenón comings such as high cost, the use of trained personnel, tedi- CIBER de Bioingeniería ous sample pretreatment, and so on. As an alternative to these Biomateriales yNanomedicina (CIBER-BBN) traditional techniques, the design of molecular probesfor the [c] Prof. R. Martínez-MµÇez,Dr. F. Sancenón undemandingchromo- and fluorogenic detection of illicit Departmento de Química, Universitat Politcnica de Valncia drugs can be of importance.Both chromogenic and fluorogen- Camí de Vera s/n, 46022Valncia (Spain) E-mail:[email protected] ic probes provideseveral advantages over other traditional an- [+] These authors contributed equally to this work. alytical techniques, such as their chemical simplicity,ease of The ORCID identification number(s) for the author(s) of this article can use, rapid response suitable forreal-time on-sitedetection, be found under:https://doi.org/10.1002/open.201800034. easy detection to the naked eye, and so on.[10] Despite these 2018 The Authors. Published by Wiley-VCH Verlag GmbH &Co. KGaA. remarkable features, the development of chromo- and fluoro- This is an openaccessarticleunder the termsofthe Creative Commons genic sensors for the selective andsensitive detection of cer- Attribution-NonCommercial-NoDerivs License, which permits useand tain illicit drugsisstill poorly explored. In this review,athor- distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are ough overview of chromogenicand fluorogenic sensing sys- made. tems for the detection of most consumed drugs is provided. ChemistryOpen 2018, 7,401 –428 www.chemistryopen.org 402 2018 The Authors. PublishedbyWiley-VCH Verlag GmbH &Co. KGaA, Weinheim The review is organized by the description of probes for differ- Table 1contains asummary of the different strategies for ent drugs classifiedaccording to their pharmacologic behavior, the chromo- and fluorogenic detection of illicit drugs used in that is, depressants, stimulants, hallucinogenic, and opioids. the examples described below. Eva MaríaGarrido graduated in Sameh El Sayed received his Masters chemistry from the University of Sevilla Degree in chemistry from the Poly- (US) in 2015 and received her Masters technic University of Valencia (Spain) Degree (Masters in Food Technology in 2012 and his Ph.D. degree from the and Industry) from the University of same university in 2015 with Professor Seville (US) in 2016. She is aPh.D. stu- RamónMartínez-MµÇez. After apost- dent at the Polytechnic University of doctoral period at University of Pavia Valencia (UPV), and her area of interest (Italy), he joined Centro de Investiga- is the development of chemical sen- ciónBiomØdica en Red (CIBER) under a sors and probes based on the use of Juan de la Cierva postdoctoral fellow- gated nanomaterials. ship for two years. His research areas of interest fall in the fields of chromo- and fluorogenic sensors and molecular probes for the detection of anions, cations, and neutral species, in addition to the develop- ment of nanomaterials for sensing and smart-delivery applications. Luis Pla graduated in chemistry from Ramon Martínez-MµÇez was born in the University of Valencia (UV) in 2013 Valencia, Spain. He received his Ph.D. and received his Masters Degree (Mas- degree in Chemistry from the Universi- ters in Experimental and Industrial Or- ty of Valencia in 1986 and was apost- ganic Chemistry) from the University doctoral fellowship at Cambridge Uni- of Valencia (UV), University of Barcelo- versity,U.K. Presently,heisafull pro- na, Polytechnic University of Valencia, fessor in the Department of Chemistry Cardenal Herrera University (CEU), and at the Polytechnic University of Valen- University of the Balearic Islands in cia and is also the director of the IDM 2014. He is aPh.D. student at the Poly- Research Institute at the Polytechnic technic University of Valencia (UPV), University of Valencia and the Biomedi- and his area of interest is the develop- cal Research Networking center in Bio- ment of chemical sensors and probes based on the use of gated engineering, Biomaterials, and Nanomedicine (CIBER-BBN). He is nanomaterials. the coauthor of more than 400 research publications and 20 pat- ents. His current research interest involves designing gated hybrid materials for on-command delivery applications. He is also involved in developing new sensing methods for different chemicals of interest. Beatriz Lozano-Torres graduated in Felix Sancenónwas born in 1968 in chemistry from the Complutense Uni- Manises,