α-Pyrrolidinohexanophenone (α-PHP) vs. α-pyrrolidinoisohexanophenone (α-PiHP): A toxicological investigation about plasma concentrations and behavior in forensic routine cases.

New psychoactive substances (NPS), like pyrrolidinophenones, are still very present on the illegal drug market. The presented study reports on two members of this substance group, α-pyrrolidinohexanophenone (α-PHP) and α-pyrrolidinoisohexanophenone (α-PiHP), which occurred in forensic routine cases in the last 6 years. α-PHP could be detected predominantly by a validated liquid chromatography-tandem mass spectrometry (LC-MS-MS) method in 33 authentic human plasma samples and α-PiHP in 8. α-PHP concentrations ranged from ca. 0.75 to 128 µg/L (mean: 23.2, median: 16.3) and α-PiHP concentrations from 7.33 to 118 µg/L (mean: 44.7, median: 33.7, quantified via α-PHP). Individuals were predominantly male and middle aged. As different studies have shown, some pyrrolidinophenones are able to cause aggressive behavior. Therefore, we set out to investigate the relation of α-PHP and α-PiHP plasma concentrations and the behavior of the consumers, reported by police and medical experts. Part of the subjects showed aggressive behavior, including agitation and restlessness. Lethargic and unremarkable behavior might be explained by co-consumption of other drugs, such as opiates/opioids, benzodiazepines, pregabalin or alcohol as well as by drug tolerance and subacute effects of stimulants. Multi-drug use could be detected in all cases; also stimulating substances and multiple different pyrrolidinophenones were determined. Nevertheless, users of α-PHP and α-PiHP showed a tendency to act aggressively, possibly triggered by a high selectivity for dopamine transporter inhibition. In accordance, committed offenses were often violent crimes. This might be considered in terms of toxicological assessment of criminal responsibility and driving ability.

Alpha-Pyrrolidinopentiothiophenone (α-PVT): A forensic case study including plasma concentrations.

Alpha-Pyrrolidinopentiothiophenone (α-PVT) belongs to the drug class of pyrrolidinophenones, a subgroup of synthetic cathinones, which are among the most prevalent new psychoactive substances. The study describes a series of 44 authentic forensic cases with analytical confirmed intake of α-PVT. Plasma concentrations, determined by a validated LC-MS/MS method, ranged from ca. 0.9 to 306 µg/L (median 35.6; mean 66.6 µg/L). Comprehensive toxicological analysis proved excessive co-consumption in almost all cases, including other pyrovalerones and classic stimulants as well as central depressant drugs such as opiates/opioids, benzodiazepines, pregabalin and/or ethanol. Subjects were aged between 26 and 54 years (median 35 years, mean 36 years) and appeared to be mainly experienced intravenous drug consumers. A high incidence of aberrant behavior in terms of aggressive, combative behavior and psychotic changes could be observed, as also reflected in accused offences, which frequently presented violent crimes. In consideration of several confounding factors, the study suggests a relationship between frequency of such impairment and plasma concentrations of α-PVT, but individual cases without signs of behavioral changes and high plasma concentrations also occurred, which might be explained by developed tolerance and/or individual vulnerably for the psychotic effects of pyrovalerones.

MDPV in forensic routine cases: Psychotic and aggressive behavior in relation to plasma concentrations.

The new psychoactive substance 3,4-methylenedioxypyrovalerone (MDPV) belongs to the group of synthetic cathinones and is purchased mainly as "research chemical" or "bath salt" on the illegal drug market, also in South Bavaria. MDPV was detected in blood and urine samples from 2010 on in 50 authentic routine cases in a forensic setting. Plasma concentrations in 46 cases with available blood specimens ranged from approximately 1.0 to 301µg/L (median 23.7; mean 47.9µg/L), detected by a fully validated LC-MS/MS method. Subjects aged between 16 and 54 years (median 36; mean 35 years) and reflected experienced chronic drug users. Accused offences were mainly violent crimes such as bodily harm, robberies, homicides and acts of resistance. A lot of subjects showed highly aggressive and violent behavior with endangerment of self and others and/or psychotic symptoms as confusion, hallucinations or paranoia. The risk for such behavior rises with MDPV plasma concentrations above as low as 30µg/L, whereby a time interval of 1.5h on average between incident and/or observation of impairment and blood sampling has to be taken into account. Comprehensive toxicological analysis proved poly-drug use in almost all cases including opiates/opioids, benzodiazepines and other sedatives, antidepressants and other stimulants, also other new psychoactive substances. Alcohol was detected only in three cases. Co-consumed benzodiazepines seem not be able to completely prevent psychotic effects despite their use as first-line treatment for patients with synthetic cathinone poisonings. The study demonstrates that relatively low plasma concentrations of MDPV could be associated with mental impairment which is relevant in the assessment of forensic cases.

Photoinduced linkage isomerism of {RuNO}(6) complexes with bioligands and related chelators.

Five novel complexes containing the {RuNO}(6) fragment and the anions derived from l-histidine (l-his), rac-3-amino-alanine (rac-dap), kojic acid (koj), methyliminodiacetic acid (mida), and thiodiacetic acid (tda) have been synthesised and characterised by single-crystal X-ray diffraction analysis, mass spectrometry, spectroscopic methods (NMR, UV-vis, IR) and elemental analysis. In the irradiated complexes, [Ru(NO)Cl(2)(l-his)] (1), [Ru(NO)Cl(2)(rac-dap)] (2), K[Ru(NO)Cl(3)(koj)] (3), K[Ru(NO)Cl(2)(mida)].(1/2)H(2)O (4), and K[Ru(NO)Cl(2)(tda)].H(2)O (5), the existence of the photoinduced long-lived metastable isonitrosyl state S1 and/or the side-on-bonded S2 state were detected by differential scanning calorimetry (DSC) and/or IR spectroscopy. For all complexes 1-5 full geometry optimisation, frequency analysis and calculation of the isotropic magnetic shielding tensors have been conducted in the framework of DFT theory.