L. Nitin Seetohul

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.

Liquid-phase broadband cavity-enhanced absorption spectroscopy measurements in a 2 mm cuvette.

A novel implementation of broadband cavity enhanced absorption spectroscopy (BBCEAS) has been used to perform sensitive visible wavelength measurements on liquid-phase solutions in a 2 mm cuvette placed at normal incidence to the cavity mirrors. The overall experimental methodology was simple, low cost, and similar to conventional ultraviolet-visible absorption spectroscopy. The cavity was formed by two concave high reflectivity mirrors. Three mirror sets with nominal reflectivities (R) of R = 0.99, 0.9945, and 0.999 were used. The light source consisted of a high intensity red, green, blue, or white LED. The detector was a compact charge-coupled device (CCD) spectrograph. Measurements were made on the representative analytes, Ho3+, and the dyes brilliant blue-R, sudan black, and coumarin 334 in appropriate solvents. Cavity enhancement factors (CEF) of up to 104 passes for the high reflectivity mirrors were obtained. The number of passes was limited by relatively high scattering and absorption losses in the cavity, of ∼1 × 10−2 per pass. Measurements over a wide wavelength range (420–670 nm) were also obtained in a single experiment with the white LED and the R = 0.99 mirror set for Ho3+ and sudan black. The sensitivity of the experimental setup could be determined by calculating the minimum detectable change in the absorption coefficient αmin. The values ranged from 5.1 × 10−5 to 1.2 × 10−3 cm−1. The limit of detection (LOD) for the strong absorber brilliant blue-R was 620 pM. A linear dynamic range of measurements of concentration over about two orders of magnitude was demonstrated. The overall sensitivity of the experimental setup compared very favorably with previous generally more experimentally complex and expensive liquid-phase cavity studies. Possible improvements to the technique and its applicability as an analytical tool are discussed.

Liquid-phase broadband cavity enhanced absorption spectroscopy (BBCEAS) studies in a 20 cm cell

Sensitive liquid-phase measurements have been made in a 20 cm cell using broadband cavity enhanced absorption spectroscopy (BBCEAS). The cavity was formed by two high reflectivity mirrors which were in direct contact with the liquid-phase analytes. Careful choice of solvent was required to minimise the effect of background solvent absorptions. Measurements were made on the broad absorber Sudan black, dissolved in acetonitrile, using a white LED light source and R > or = 0.99 cavity mirrors, leading to a cavity enhancement factor (CEF) of 82 at 584 nm. The sensitivity as measured by the minimum detectable change in the absorption coefficient (alpha(min)) was 3.4 x 10(-7) cm(-1). Further measurements were made on the strong absorber methylene blue dissolved in acetonitrile at 655 nm. A white LED was used with the R > or = 0.99 cavity mirrors, leading to a CEF of 78 and alpha(min) = 4.4 x 10(-7) cm(-1). The use of a more intense red LED also allowed measurements with higher reflectivity R > or = 0.999 cavity mirrors, leading to a CEF of 429 and alpha(min) = 2.8 x 10(-7) cm(-1). The sensitivity was limited by dark noise from the detector but nevertheless appears to represent the most sensitive liquid-phase absorption measurement to date.

Analysis of phenazepam and 3-hydroxyphenazepam in post-mortem fluids and tissues.

Phenazepam is a benzodiazepine that is predominantly used clinically in the former Soviet states but is being abused throughout the wider world. This study reports the tissue distribution and concentration of both phenazepam and 3-hydroxyphenazepam in 29 cases quantitated by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in a variety of post-mortem fluids (subclavian blood, femoral blood, cardiac blood, urine, vitreous humour) and tissues (thalamus, liver and psoas muscle). In 27 cases, the cause of death was not directly related to phenazepam (preserved (fluoride/oxalate) femoral blood phenazepam concentrations 0.007 mg/L to 0.360 mg/L (median 0.097 mg/L). In two cases, phenazepam was either a contributing factor to, or the certified cause of death (preserved (fluoride/oxalate) femoral blood 0.97 mg/L and 1.64 mg/L). The analysis of phenazepam and 3-hydroxyphenazepam in this study suggests that they are unlikely to be subject to large post-mortem redistribution and that there is no direct correlation between tissues/fluid and femoral blood concentrations. Preliminary investigations of phenazepam stability comparing femoral blood phenazepam concentrations in paired preserved (2.5% fluoride/oxalate) and unpreserved blood show that unpreserved samples show on average a 14% lower concentration of phenazepam and we recommend that phenazepam quantitation is carried out using preserved samples wherever possible.

Discrimination of Sri Lankan black teas using fluorescence spectroscopy and linear discriminant analysis.

BACKGROUND The quality of teas is currently graded using trained tea tasters, whose evaluation can sometimes be subjective. In this study the simple fluorescence-based technique of total luminescence spectroscopy (TLS) in conjunction with data classification using principal component analysis (PCA) was applied to discriminate between teas from 11 different Sri Lankan plantations. Solvent extraction of the tea samples was followed by TLS to record excitation-emission matrices in the excitation range 250-590 nm and emission range 300-700 nm. RESULTS The application of PCA and linear discriminant analysis (LDA) allowed the successful classification of all 11 teas using only the first two principal components. LDA demonstrated how the technique was able to discriminate between all teas correctly with 100% classification. CONCLUSION Further development of this work could lead to a simple device that could be used by tea manufacturers instead of or alongside trained tea tasters to grade teas.

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 …

Stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solution.

Occasionally, the only postmortem samples available for analysis are contaminated with formaldehyde, either due to embalming prior to sampling or because analysis is carried out only when formalin-fixed tissues retained for histological study are available. Formaldehyde reacts with several drugs of forensic interest that contain either a primary or a secondary amine group to form their N-methyl derivatives. We investigated the stability of 3,4-methylenedioxymethampetamine (MDMA), 4-methylmethcathinone (mephedrone) and 3-trifluromethylphenylpiperazine (3-TFMPP) in formalin solutions using three different formaldehyde concentrations (5, 10 and 20%) and three different pHs (3.0, 7.0 and 9.5). Analysis was performed using high-performance liquid chromatography with diode array detection to determine the percentage degradation of each drug over time, up to 60 days. MDMA, mephedrone and 3-TFMPP are unstable in formalin solutions, with the degradation rate increasing with increasing pH. After 28 days in 20% formalin, pH 9.5, there remained 57% of the initial 3-TFMPP concentration, 11% of the initial MDMA concentration and 4% of the initial mephedrone concentration. Forensic toxicologists should be aware that, when analyzing for these drugs in an embalmed body or in tissues stored in formalin solutions, the methylated form of the secondary amine-containing drug could be a more useful analyte than the parent drug.

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).

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.