4-Fluoroamphetamine (4-FA). Critical Review Report.

1-(4-Fluorophenyl)propan-2-amine (4-fluoroamphetamine, 4-FA) is a psychomotor stimulant that was first synthesized in the early 1940s. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) received the first formal notification of the detection of 4-FA in Europe in December 2008 although its presence has been noted since at least 2007. In Europe, it has been found in tablets sold as ‘ecstasy’/MDMA, paste or powder sold as amphetamine. In addition, it can be obtained from Internet retailers as a ‘research chemical’ and it has also been detected as an adulterant present in other illicit controlled substances. 4-FA appears to be most commonly administered orally or by nasal insufflation (snorting). The EMCDDA has been notified of seizures from various locations in Europe since 2008. Data indicate that 4-FA may be able to inhibit monoamine oxidase and that it functions as a substrate-type releasing agent of dopamine, norepinephrine and serotonin. It has been shown to display amphetamine-like features in vivo and in vitro and further research is warranted to investigate the extent to which 4-FA displays a potential for abuse and dependence in both animals in humans that is comparable to substances such as amphetamine, cocaine or related psychostimulants. Case report data in the scientific literature that unambiguously confirm a causal relationship between adverse effects of 4-FA and its presence in biofluids are limited to only a relatively small number of cases. In cases where this information is available, reported clinical features were associated with those of a sympathomimetic toxidrome. The EMCDDA has received reports from positive identifications in biofluids samples from 2009 onward. It has been reported that 4-FA might have established itself as a drug of choice in a surveyed convenience sample of 249 life-time users of 4-FA in one European country. Surveys that systematically assess the prevalence of use 4-FA within the general population are not available

4-Fluoroamphetamine (4-FA). A Critical Review Report

1-(4-Fluorophenyl)propan-2-amine (4-fluoroamphetamine, 4-FA) underwent a critical review in November 2015 at the 37th meeting of the WHO Expert Committee on Drug Dependence. The Committee recommended that 4-FA not be placed under international control at that time due to insufficiency of data regarding dependence, abuse and risks to public health but be kept under surveillance. This review represents an update. 4-FA is a psychomotor stimulant first synthesized in the early 1940s. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) received the first formal notification of the detection of 4-FA in Europe in December 2008 although its presence has been noted since at least 2007. In Europe, it has been found in tablets sold as ‘ecstasy’/MDMA, paste or powder sold as amphetamine. It has also been detected as an adulterant present in other illicit controlled substances. The EMCDDA has been notified of seizures from various locations in Europe since 2008. In the Netherlands, 4-FA has recently established itself as a drug of choice (powdered form, tablets and capsules) in a subpopulation of recreational drug users associated with clubs and music festivals. 4- FA appears to be most commonly administered orally or by nasal insufflation (snorting). Data indicate that 4-FA may be able to inhibit monoamine oxidase and that it functions as a substrate-type releasing agent of dopamine, norepinephrine and serotonin. It has been shown to display amphetamine-like features in vivo and in vitro, which suggests that abuse liability might extend to humans. Further research is warranted to investigate the extent to which 4-FA displays a potential dependence in both animals in humans. Case report data in the scientific literature that unambiguously confirm a causal relationship between adverse effects of 4-FA and its presence in biofluids are limited to only a relatively small number of cases. In cases where this information is available, reported clinical features were associated with those of a sympathomimetic toxidrome. Information about a global perspective is missing. However, reports received from data monitoring systems in the Netherlands indicate increased use and popularity alongside increased numbers of notifications associated with severe adverse drug effects including serious cardiovascular toxicity. Following a risk assessment carried out by the Dutch Centre for the Assessment and Monitoring of new drugs (CAM), it was concluded that the risk to individual health was small to moderate but with high risk for acute toxicity especially in subpopulations associated with clubbing. The risk to public health was deemed moderate to large based on rising trends in use number of health incidents. The overall risk score of 4-FA was considered high, which led to 4-FA being placed under legislative control

Development and applications of proton transfer reaction-mass spectrometry for homeland security: trace detection of explosives

This thesis investigates the challenging task of sensitive and selective trace detection of explosive compounds by means of proton transfer reaction mass spectrometry (PTR-MS). In order to address this, new analytical strategies and hardware improvements, leading to new methodologies and analytical tools, have been developed and tested. These are, in order of the Chapters presented in this Thesis, the switching of reagent ions, the implementation of a novel thermal desorption unit, and the use of an ion funnel drift tube or fast reduced electric field switching to modify the ion chemistry. In addition to these, a more fundamental study has been undertaken to investigate the reactions of picric acid with a number of different reagent ions. The novel approaches described in this thesis have improved the PTR-MS technique by making it more versatile in terms of its analytical performance, namely providing assignment of chemical compounds with high confidence. These techniques are going to be employed in the new generation of PTR-MS instruments being developed by KORE Technology Ltd. Although demonstrated for Homeland Security in this thesis, the developments made can be utilised for improved selectivity in areas such as atmospheric chemistry, and in the environmental, food and health sciences