Giorgia De Paoli

Phenazepam: The drug that came in from the cold

In the past few years there has been concern in Western Europe and in the US about the rise in abuse of phenazepam, a benzodiazepine that was originally developed in the USSR in the mid- to late 1970s.(1-4) Although phenazepam is one of the most widely prescribed benzodiazepines in Russia and other commonwealth of independent state (CIS) countries, it has not been licensed elsewhere in the world. Due to very limited licensed geographical distribution, there is very little peer-reviewed literature that is not written in Russian. In this article, we review the current state of what is currently known about phenazepam. This information on phenazepam and how it can be detected in biological specimens should assist the forensic community in identifying phenazepam in routine toxicology screening and interpreting any phenazepam concentrations that are obtained.

Naphyrone: analytical profile of the new "legal high" substitute for mephedrone.

Dear Editor, Mephedrone (4-methylmethcathinone) has been banned recently in several countries, including the UK as from April 2010. Banning of the drug in the UK followed a report from the Advisory Council on the Misuse of Drugs1 and newspaper reports of several deaths linked to mephedrone.2 Soon after mephedrone was banned, internet sites3 began to market a new legal alternative – naphyrone, which is also known as NRG-1. The structure of this new designer drug is similar to that of pyrovalerone, a monoamine uptake inhibitor, first synthesized in 1964.4 As with mephedrone, presently there is no safety or toxicity data available for naphyrone, which in its turn has now been banned in the UK as from July 12, 2010.5 Anticipating the problem of having to identify the drug in routine forensic toxicology drug screens, we purchased naphyrone from a website, since it is not available as a pure standard from certified sources. Analysis of he drug undertaken by HPLC-DAD, GC-MS and LC-MS-MS using our current standard laboratory drug screening methods has produced a useful analytical profile for naphyrone. Detailed analytical data and naphyrone’s UV and mass spectra can be found at: http://www.dundee.ac.uk/forensicmedicine/drugmonographs/naphyrone. This analytical data should assist the wider forensic community in identifying naphyrone in routine toxicology screening.

Preparation and analytical characterization of 1-(1-phenylcyclohexyl)piperidine (PCP) and 1-(1-phenylcyclohexyl)pyrrolidine (PCPy) analogues

Classic examples of psychoactive arylcycloalkylamines include ketamine and 1-(1-phenylcyclohexyl)piperidine (PCP) and many others serve as important structural templates for neuropharmacological research. The recent emergence of PCP analogues that can be obtained from internet retailers requires the implementation of appropriate monitoring strategies for harm reduction purposes. Access to analytical data plays a key part when encountering these substances, especially if reference material is not available. The present study describes the synthesis of three substituted 1-(1-phenylcyclohexyl)piperidines, (3-MeO-, 4-MeO- and 3-Me-PCP) and three substituted 1-(1-phenylcyclohexyl)pyrrolidine analogues (3-MeO-, 4-MeO- and 3-Me-PCPy). Analytical characterizations of all six arylcyclohexylamines and their primary 1-phenylcyclohexanamine intermediates included gas chromatography ion trap electron- and chemical ionization and high resolution mass spectrometry, liquid chromatography electrospray hybrid triple-quadrupole linear ion trap tandem mass spectrometry, infrared, diode array detection and (1) H and (13) C nuclear magnetic resonance (NMR) spectroscopy. Solvent (CDCl3 vs. d6 -DMSO) and protonation effects (free bases vs hydrochloride salts) were studied in order to investigate the impact on shifts and splitting patterns, for example, when attempting to assign separate axial and equatorial proton chemical shifts of NMR spectra. Differentiation between the isomeric 3-MeO-/4-MeO-PCP and PCPy analogues was feasible under mass spectral conditions. Gas chromatography analysis appeared to induce notable degradation of the 4-MeO-substituted analytes, especially when dealing with the HCl salts which led to the detection of the substituted 1-phenylcyclohex-1-ene nucleus. This phenomenon was observed to be less pronounced with the 3-MeO isomers, possibly due to the resonance properties of the para-methoxy group followed by more facile elimination of the amine.

Phenazepam is currently being misused in the UK

Phenazepam is a benzodiazepine not currently controlled in the United Kingdom, mainland Europe, or the United States. Developed in the 1970s for the treatment of epilepsy, alcohol withdrawal syndrome, insomnia, and anxiety,1 2 it is currently prescribed only in the former Soviet Bloc. However, recent reports from Sweden, Finland, and the …

Deaths associated with new designer drug 5-IT

5-IT or 5-API is the common name for a newly emerging designer drug.1 It is a positional isomer of the tryptamine drug α-methyltryptamine and has the chemical structure (1H-indol-5-yl)propan-2-amine. Currently not controlled in Europe, it is covered, however, by the federal analogue acts in the USA2 …

Banned but still available on the internet

Before April 2010, when mephedrone became a class B substance in the UK, the drug was sold lawfully online, either using its correct name or under fantasy names that did not specify its presence.1 A recent study has reported the …

Biomarkers for Illicit Heroin: A Previously Unrecognized Origin of Papaverine

In forensic toxicology, the detection of biomarkers for illicit heroin is important in the identification of illicit opiate use. In addition to the active metabolite 6-monoacetylmorphine, the opiate codeine and the major impurity acetylcodeine, other biomarkers such as papaverine, noscapine and their metabolites have been proposed (1, 2, 3, 4).

Nefopam Hydrochloride: A Fatal Overdose

Nefopam is a non-opiate analgesic commonly used for the treatment of moderate to severe pain. A case of a 37-year-old male who was found dead in the morning is presented. An autopsy was performed and femoral venous blood, heart blood, urine, and vitreous humor were submitted for toxicological analysis. A general drug screen detected the presence of nefopam, caffeine, nicotine, citalopram, gabapentin, amitriptyline, diazepam and paracetamol in cardiac blood. Nefopam was quantitated by high-performance liquid chromatography with diode-array detection. Nefopam was found at the following concentrations: 13.6 mg/L in unpreserved femoral blood; 14.7 mg/L in preserved (fluoride-oxalate) femoral blood; 21.2 mg/L in unpreserved cardiac blood and 4.5 mg/L in preserved vitreous. Citalopram was present at a concentration of 0.7 mg/L (femoral blood) and 0.9 mg/L (cardiac blood). Ethanol analyzed by headspace gas chromatography (GC-FID) was detected in preserved (fluoride-oxalate) vitreous (14 mg/100 mL) and preserved (fluoride-oxalate) urine 50 mg/100 mL. Death was attributed to atherosclerotic coronary artery disease and therapeutic drug toxicity.

Meptazinol and Ethanol: A Fatal Intoxication

Meptazinol (Meptid(®)) is an analgesic drug that is used to treat mild to moderate pain including postoperative pain, obstetrical pain, and the pain of renal colic. This case reports a death due to the combined effects of meptazinol and alcohol in a man with significant heart disease and alcoholic liver disease. A 57-year-old male was found unresponsive in his bed at home with empty blister packets of meptazinol around him. A general drug screen detected the presence of meptazinol, and caffeine and metabolites, in cardiac blood. Analysis, both quantitative (HPLC-DAD) and qualitative (HPLC-DAD, LC-MS), of meptazinol was carried out. Meptazinol was found at the following concentrations: 15.5 mg/L in unpreserved femoral blood; 18.6 mg/L in preserved (fluoride-oxalate) femoral blood; 52.1 mg/L in unpreserved cardiac blood; 16.8 mg/L in preserved vitreous; 61.7 mg/L in unpreserved urine; and 9.8 g/L in stomach contents. Ethanol, analyzed by headspace GC-FID, was present in preserved (fluoride-oxalate) femoral venous blood, urine, and vitreous at concentrations of 232 mg/100 mL, 297 mg/100 mL, and 192 mg/100 mL, respectively. Death was attributed to meptazinol and ethanol toxicity, with atherosclerotic coronary artery disease as a contributing factor.