Uncertainty in Widmark calculations:ABV variation in packaged versions of the most popular beers in the UK

Forensic practitioners regularly use the Widmark equation to determine theoretical blood alcohol concentrations for use in cases involving alcohol. It is important in these calculations to determine the uncertainty associated with any result. Previous work has investigated the uncertainty in %ABV from beers produced by small independent breweries in the UK but did not study the top selling beers. The top selling lagers and ales/bitters in the UK were identified by sales volume and the alcohol by volume determined. This data was then used to determine the percent coefficient of variation (%CV) that should be used by forensic practitioners when constructing alcohol technical defence reports for use in forensic cases. These samples, from what may be described as ‘big’ brewers, were determined to have a smaller root mean square error (RMSE) (±0.1%v/v, n = 35), and %CV than those previously reported for beers produced by small, independent breweries in the UK. The results from this study shows that different RMSE's should be used for %ABV when determining the uncertainty of results from Widmark calculations when drinks have been consumed from either ‘big’ brewers or small, independent breweries

Improving uncertainty in Widmark equation calculations:alcohol volume, strength and density

The Widmark equation is probably the most commonly used calculation for medicolegal purposes. Recently the National Research Council (USA) and the Forensic Science Regulator (UK) have called for the uncertainty of all results to be given with all forensic measurements and calculations. To improve the uncertainty of measurement of results from Widmark calculations we have concentrated on the uncertainties of measurement involved in the calculation of alcohol, that of the volume of alcohol, the concentration of alcohol and the density of alcohol as previous studies have investigated some of the other factors involved . Using experimental studies, the scientific literature and legal statutes, we have determined revised and improved uncertainties of the concentration of ethanol for Widmark calculations for both the USA and UK. Based on the calculations that we have performed we recommend the use of Monte Carlo Simulation for the determination of uncertainty of measurement for Widmark Calculations

Experimental versus theoretical log D_7.4, pK_a and plasma protein binding values for benzodiazepines appearing as new psychoactive substances

The misuse of benzodiazepines as new psychoactive substances is an increasing problem around the world. Basic physicochemical and pharmacokinetic data is required on these substances in order to interpret and predict their effects upon humans. Experimental log D7.4, pKa and plasma protein binding values were determined for 11 benzodiazepines that have recently appeared as new psychoactive substances (3‐hydroxyphenazepam, 4’‐chlorodiazepam, desalkylflurazepam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, phenazepam and pyrazolam) and compared with values generated by various software packages (ACD/I‐lab, MarvinSketch, ADMET Predictor and PreADMET). ACD/I‐LAB returned the most accurate values for log D7.4 and plasma protein binding while ADMET Predictor returned the most accurate values for pKa. Large variations in predictive errors were observed between compounds. Experimental values are currently preferable and desirable as they may aid with the future ‘training’ of predictive models for these new psychoactive substances

The influence of alcohol content variation in UK packaged beers on the uncertainty of calculations using the Widmark equation

It is common for forensic practitioners to calculate an individual's likely blood alcohol concentration following the consumption of alcoholic beverage(s) for legal purposes, such as in driving under the influence (DUI) cases. It is important in these cases to be able to give the uncertainty of measurement on any calculated result, for this reason uncertainty data for the variables used for any calculation are required. In order to determine the uncertainty associated with the alcohol concentration of beer in the UK the alcohol concentration (%v/v) of 218 packaged beers (112 with an alcohol concentration of ≤5.5%v/v and 106 with an alcohol concentration of >5.5%v/v) were tested using an industry standard near infra-red (NIR) analyser. The range of labelled beer alcohol by volume (ABV's) tested was 3.4%v/v – 14%v/v. The beers were obtained from a range of outlets throughout the UK over a period of 12 months. The root mean square error (RMSE) was found to be ±0.43%v/v (beers with declared %ABV of ≤5.5%v/v) and ±0.53%v/v (beers with declared %ABV of >5.5%v/v) the RMSE for all beers was ±0.48%v/v. The standard deviation from the declared %ABV is larger than those previously utilised for uncertainty calculations and illustrates the importance of appropriate experimental data for use in the determination of uncertainty in forensic calculations

Application of a Bayesian network to aid the interpretation of blood alcohol (ethanol) concentrations in air crashes

In the investigation of a fatal air crash, it is important to determine if the pilot, at the time of death, was contravening the regulations in relation to 1) the permitted concentration of ethanol (alcohol) in the blood and 2) whether the pilot had consumed alcohol within a specified period before flying. It is also important to assess whether any alcohol detected in the toxicological samples was present either because of consumption or because of post-mortem alcohol formation. We have developed a Bayesian Network that models the relationships between analytical results, circumstantial evidence and the concentration of alcohol at the time of death in cases of air crash. The model provides a rational, coherent approach to forensic interpretation, moving interpretation from a largely subjective, generalist approach to a more objective, case-specific methodology utilising available relevant data and accommodating the inevitable uncertainties within a case

Phenazepam: More information coming in from the cold

Phenazepam is a 1-4 benzodiazepine that was developed in 1975 in the former USSR this article updates what is known about the pharmacokinetics of Phenazepam

The use of a quantitative structure-activity relationship (QSAR) model to predict GABA-A receptor binding of newly emerging benzodiazepines

The illicit market for new psychoactive substances is forever expanding. Benzodiazepines and their derivatives are one of a number of groups of these substances and thus far their number has grown year upon year. For both forensic and clinical purposes it is important to be able to rapidly understand these emerging substances. However as a consequence of the illicit nature of these compounds, there is a deficiency in the pharmacological data available for these ‘new’ benzodiazepines. In order to further understand the pharmacology of ‘new’ benzodiazepines we utilised a quantitative structure-activity relationship (QSAR) approach. A set of 69 benzodiazepine-based compounds was analysed to develop a QSAR training set with respect to published binding values to GABAA receptors. The QSAR model returned an R2 value of 0.90. The most influential factors were found to be the positioning of two H-bond acceptors, two aromatic rings and a hydrophobic group. A test set of nine random compounds was then selected for internal validation to determine the predictive ability of the model and gave an R2 value of 0.86 when comparing the binding values with their experimental data. The QSAR model was then used to predict the binding for 22 benzodiazepines that are classed as new psychoactive substances. This model will allow rapid prediction of the binding activity of emerging benzodiazepines in a rapid and economic way, compared with lengthy and expensive in vitro/in vivo analysis. This will enable forensic chemists and toxicologists to better understand both recently developed compounds and prediction of substances likely to emerge in the future