Assessment of a Single Quadrupole Mass Spectrometer Combined with an Atmospheric Solids Analysis Probe for the On-Site Identification of Amnesty Bin Drugs.

The surging number of people who abuse drugs has a great impact on healthcare and law enforcement systems. Amnesty bin drug analysis helps monitor the "street drug market" and tailor the harm reduction advice. Therefore, rapid and accurate drug analysis methods are crucial for on-site work. An analytical method for the rapid identification of five commonly detected drugs ((3,4-methylenedioxymethamphetamine (MDMA), cocaine, ketamine, 4-bromo-2,5-dimethoxyphenethylamine, and chloromethcathinone)) at various summer festivals in the U.K. was developed and validated employing a single quadrupole mass spectrometer combined with an atmospheric pressure solids analysis probe (ASAP-MS). The results were confirmed on a benchtop gas chromatography-mass spectrometry instrument and included all samples that challenged the conventional spectroscopic techniques routinely employed on-site. Although the selectivity/specificity step of the validation assessment of the MS system proved a challenge, it still produced 93% (N = 279) and 92.5% (N = 87) correct results when tested on- and off-site, respectively. A few "partly correct" results showed some discrepancies between the results, with the MS-only unit missing some low intensity active ingredients (N-ethylpentylone, MDMA) and cutting agents (caffeine, paracetamol, and benzocaine) or detecting some when not present. The incorrect results were mainly based on library coverage. The study proved that the ASAP-MS instrument can successfully complement the spectroscopic techniques used for qualitative drug analysis on- and off-site. Although the validation testing highlighted some areas for improvement concerning selectivity/specificity for structurally similar compounds, this method has the potential to be used in trend monitoring and harm reduction.

In Vitro Neurochemical Assessment of Methylphenidate and Its "Legal High" Analogs 3,4-CTMP and Ethylphenidate in Rat Nucleus Accumbens and Bed Nucleus of the Stria Terminalis.

3,4-dichloromethylphenidate (3,4-CTMP) and ethylphenidate are new psychoactive substances and analogs of the attention deficit medication methylphenidate. Both drugs have been reported on online user fora to induce effects similar to cocaine. In the UK, 3,4-CTMP appeared on the drug market in 2013 and ethylphenidate has been sold since 2010. We aimed to explore the neurochemical effects of these drugs on brain dopamine and noradrenaline efflux. 3,4-CTMP and ethylphenidate, purchased from online vendors, were analyzed using gas chromatography and mass spectroscopy to confirm their identity. Drugs were then tested in adolescent male rat brain slices of the nucleus accumbens and stria terminalis for effects on dopamine and noradrenaline efflux respectively. Fast cyclic voltammetry was used to measure transmitter release. Methylphenidate (10 µM) increased evoked dopamine and noradrenaline efflux by 4- and 2-fold, respectively. 3,4-CTMP (0.1 and 1 µM) increased evoked dopamine and noradrenaline efflux by ~6-fold and 2-fold, respectively. Ethylphenidate (1 µM) doubled evoked dopamine and noradrenaline efflux in both cases. 3,4-CTMP's effect on dopamine efflux was greater than that of methylphenidate, but ethylphenidate appears to be a weaker dopamine transporter inhibitor. Experiments using the dopamine D2 antagonist haloperidol, the noradrenaline α2 receptor antagonist yohimbine, the dopamine transporter inhibitor GBR12909 and the noradrenaline transporter inhibitor desipramine confirmed that we were measuring dopamine in the accumbens and noradrenaline in the ventral BNST. All three psychostimulant drugs, through their effects on dopamine efflux, may have addictive liability although the effect of 3,4-CTMP on dopamine suggests that it might be most addictive and ethylphenidate least addictive.

The impact of changes in UK classification of the synthetic cannabinoid receptor agonists in 'Spice'.

BACKGROUND: Spice is the iconic brand name of a smokeable herbal mixture containing synthetic cannabinoid receptor agonists. It has been available on the Internet/in head shops in Europe since at least 2006. The synthetic cannabinoid receptor agonist constituents of Spice were classified in the UK as Class B agents in December 2009. This study assessed the impact of this legislation on the synthetic cannabinoid receptor agonists present in Spice products and whether new synthetic cannabinoid receptor agonists outside of the legislation are now available. METHODS: Spice products were bought, prior to and after the change in the UK legislation, from a range of Internet legal high websites selling to UK consumers. Products were analysed using liquid chromatography high-resolution tandem mass spectrometry (LCMSMS). Identification of the synthetic cannabinoid receptor agonist(s) detected was made by comparison to existing databases or by 'in silico' methods. RESULTS: Sixteen products were purchased prior to the UK control of synthetic cannabinoid receptor agonists; all contained at least one synthetic cannabinoid receptor agonist. 20 products were purchased after the UK control; no active compounds were detected in 3 (15%). The remaining 17 (85%) all contained at least one classified synthetic cannabinoid receptor agonist. Additionally, 2 synthetic cannabinoid receptor agonists not covered under current UK generic legislation (AM-694 and the 'novel Belarus compound') were detected. CONCLUSION: Despite the UK 'Spice' classification, classified synthetic cannabinoid receptor agonists continue to be supplied over the Internet to UK users. Furthermore, new synthetic cannabinoid receptor agonists not covered by the legislation are appearing. Consideration needs to be given to reviewing the UK legislation so that suppliers cannot circumvent it by supplying legal alternatives to the classified synthetic cannabinoid receptor agonists.

Impact of cough across different chronic respiratory diseases: comparison of two cough-specific health-related quality of life questionnaires.

BACKGROUND: Cough is a prominent symptom across a range of common chronic respiratory diseases and impacts considerably on patient health status. METHODS: We undertook a cross-sectional comparison of scores from two cough-specific health-related quality of life (HRQoL) questionnaires, the Leicester Cough Questionnaire (LCQ), and the Cough Quality of Life Questionnaire (CQLQ), together with a generic HRQoL measure, the EuroQol. Questionnaires were administered to and spirometry performed on 147 outpatients with chronic cough (n = 83), COPD (n = 18), asthma (n = 20), and bronchiectasis (n = 26). RESULTS: There was no significant difference in the LCQ and CQLQ total scores between groups (p = 0.24 and p = 0.26, respectively). Exploratory analyses of questionnaire subdomains revealed differences in psychosocial issues and functional impairment between the four groups (p = 0.01 and p = 0.05, respectively). CQLQ scores indicated that chronic coughers have more psychosocial issues than patients with bronchiectasis (p = 0.03) but less functional impairment than COPD patients (p = 0.04). There was a significant difference in generic health status across the four disease groups (p = 0.04), with poorest health status in COPD patients. A significant inverse correlation was observed between CQLQ and LCQ in each disease group (chronic cough r = - 0.56, p < 0.001; COPD r = - 0.49, p = 0.04; asthma r = - 0.94, p < 0.001; and bronchiectasis r = - 0.88, p < 0.001). There was no correlation between cough questionnaire scores and FEV(1) in any group, although a significant correlation between EuroQol visual analog scale component and FEV(1) (r = 0.639, p = 0.004) was observed in COPD patients. CONCLUSION: Cough adversely affects health status across a range of common respiratory diseases. The LCQ and CQLQ can each provide important additional information concerning the impact of cough.