Combined Use of Flubromazepam and Stimulants: Blood and Oral Fluid Concentrations and Impact on Driving Ability.

"Designer" benzodiazepines (DBZDs) are becoming increasingly available in Europe, with the European Monitoring Centre of Drugs and Drug Addiction currently monitoring ∼30 new benzodiazepines. The following driving under the influence of drug (DUID) case describes the oral fluid (OF) and blood concentrations, as well as the observed effects after the combined use of stimulants and flubromazepam. Both OF, collected via the Intercept i2 collector (Immunalysis, Pomona, CA, USA), and blood (collected in containers with various stabilizers) were screened using a liquid chromatographic (LC) time-of-flight (TOF) mass spectrometric (MS-MS) method.

The Interest of a Systematic Toxicological Analysis Combined with Forensic Advice to Improve the Judicial Investigation and Final Judgment in Drug Facilitated Sexual Assault Cases.

The conviction rate in drug facilitated sexual assault (DFSA) cases is known to be very low. In addition, the potential impact of toxicological results on the case is often not well understood by the judicial authorities. The aims of this study were (1) to obtain more knowledge concerning the prevalence of incapacitating substances in DFSA cases, (2) to create a more efficient DFSA analysis strategy taking background information into account, and (3) to evaluate the potential impact of systematic toxicological analysis (STA) on the final judicial outcome.

Acute Susac Syndrome in a Recent User of Adulterated Cocaine: Levamisole as a Triggering Factor?

Susac syndrome (SS) is a central nervous system vasculitis characterized by the clinical triad of encephalopathy, sensorineural hearing loss, and visual disturbance caused by branch retinal artery occlusion. It is considered as an inflammatory disorder, and an autoimmune etiology is suggested. A 29-year-old man with a history of recent cocaine abuse developed the clinical features of SS.

Driving under the influence of cocaine: Quantitative determination of basic drugs in oral fluid obtained during roadside controls and a controlled study with cocaine users.

Using the Belgian Drugs and Driving procedure, 36% of the cocaine-positive oral fluid (OF) screening results were not confirmed in plasma. This study investigates the impact of the choice of screening devices and confirmation matrix on the detection of cocaine use. An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method quantifying cocaine, benzoylecgonine (BZE), and other basic drugs in OF was developed and validated.

Crystallization: digging into the past to learn lessons for the future.

Crystals of biological macromolecules have been observed and grown for well over a century. More effort has been put into biological crystallization in the last few decades due to the importance of X-ray crystal structures, the advent of synchrotron radiation sources, improved computational speed, better software, and the availability of recombinant protein. Here we focus on two important areas of crystal growth: firstly, on techniques for stabilizing the protein sample, and secondly, on strategies and approaches for selecting the crystallization cocktails most suitable for different strategies.

Trends in drug testing in oral fluid and hair as alternative matrices.

The use of alternative matrices such as oral fluid and hair has increased in the past decades because of advances in analytical technology. However, there are still many issues that need to be resolved. Standardized protocols of sample pretreatment are needed to link the detected concentrations to final conclusions.

A drunken search in crystallization space.

The REMARK280 field of the Protein Data Bank is the richest open source of successful crystallization information. The REMARK280 field is optional and currently uncurated, so significant effort needs to be applied to extract reliable data. There are well over 15 000 crystallization conditions available commercially from 12 different vendors.

Impact of the grinding process on the quantification of ethyl glucuronide in hair using a validated UPLC-ESI-MS-MS method.

The Society of Hair Testing (SoHT) has provided cutoffs for the quantification of ethyl glucuronide (EtG) in hair to indicate occasional or chronic/excessive alcohol consumption. Although several sensitive methods have been reported, past proficiency test results show a lack of reproducibility. An ultra-performance liquid chromatographic mass spectrometric method (LLOQ of 10 pg EtG/mg hair) has been validated according to the international guidelines, including the successful participation in five proficiency tests.

A quantitative, selective and fast ultra-high performance liquid chromatography tandem mass spectrometry method for the simultaneous analysis of 33 basic drugs in hair (amphetamines, cocaine, opiates, opioids and metabolites).

Forensic testing for drugs of abuse in hair has become a useful diagnostic tool in determining chronic drug use as well as examining long-term drug history thorough segmental analysis. However, sensitive and specific analytical methods are needed. A simple, rapid and highly sensitive and specific method for the extraction and quantification of 33 opioids, opiates, cocaine, and amphetamines is presented.

Validation of an automated solid-phase extraction method for the analysis of 23 opioids, cocaine, and metabolites in urine with ultra-performance liquid chromatography-tandem mass spectrometry.

The aim of this work was to automate a sample preparation procedure extracting morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-monoacetyl-morphine, hydrocodone, ethylmorphine, benzoylecgonine, cocaine, cocaethylene, tramadol, meperidine, pentazocine, fentanyl, norfentanyl, buprenorphine, norbuprenorphine, propoxyphene, methadone and 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine from urine samples. Samples were extracted by solid-phase extraction (SPE) with cation exchange cartridges using a TECAN Freedom Evo 100 base robotic system, including a hydrolysis step previous extraction when required. Block modules were carefully selected in order to use the same consumable material as in manual procedures to reduce cost and/or manual sample transfers.

Evaluation of Δ(9) -tetrahydrocannabinol detection using DrugWipe5S(®) screening and oral fluid quantification after Quantisal™ collection for roadside drug detection via a controlled study with chronic cannabis users.

Oral fluid (OF) is potentially useful to detect driving under the influence of drugs because of its ease of sampling. While cannabis is the most prevalent drug in Europe, sensitivity issues for Δ(9) -tetrahydrocannabinol (THC) screening and problems during OF collection are observed. The ability of a recently improved OF screening device - the DrugWipe5S(®) , to detect recent THC use in chronic cannabis smokers, was studied.

Crystallization reports are the backbone of Acta Cryst. F, but do they have any spine?

Crystallization of macromolecules is famously difficult. By knowing what has worked for others, researchers can ease the process, both in the case where the protein has already been crystallized and in the situation where more general guidelines are needed. The 264 crystallization communications published in Acta Crystallographica Section F in 2012 have been reviewed, and from this analysis some information about trends in crystallization has been gleaned.

Quantitative analysis of 26 opioids, cocaine, and their metabolites in human blood by ultra performance liquid chromatography-tandem mass spectrometry.

A sensitive and selective ultra performance liquid chromatographic-tandem mass spectrometric method was developed and fully validated for the simultaneous determination of (in order of chromatographic elution) methylecgonine, pholcodine, morphine, hydromorphone, oxymorphone, norcodeine, codeine, dihydrocodeine, oxycodone, 6-Monoacetylmorphine (6-MAM), hydrocodone, ethylmorphine, norfentanyl, benzoylecgonine, tramadol, normeperidine, meperidine, cocaine, pentazocine, cocaethylene, fentanyl, norbuprenorphine, 2-ethylidine-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), buprenorphine, propoxyphene, and methadone in blood. The matrixes analyzed during the validation experiments were as follows: citrated blank plasma for calibrators, fluoride blank plasma for internal quality control (QC), lyophilized serum for external QC, fluoride plasma and whole blood for authentic samples, and lyophilized serum and whole blood for proficiency testing schemes. Samples were extracted with cation exchange solid-phase extraction cartridges.

A fully validated method for the quantification of ethyl glucuronide and ethyl sulphate in urine by UPLC-ESI-MS/MS applied in a prospective alcohol self-monitoring study.

A method for the quantification of ethyl glucuronide (EtG) and ethyl sulphate (EtS) in human urine is developed and fully validated according to international guidelines. Protein precipitation is used as sample preparation. During the development of the method on an UPLC-ESI-MS/MS system using a CSH C18 column, special attention was paid to reduce matrix effects to improve assay sensitivity and to improve detection of the second transition for EtS for specificity purposes.

Driving under the influence of cannabis: pitfalls, validation, and quality control of a UPLC-MS/MS method for the quantification of tetrahydrocannabinol in oral fluid collected with StatSure, Quantisal, or Certus collector.

Background: "Driving under the influence of drugs" (DUID) has a large impact on the worldwide mortality risk. Therefore, DUID legislations based on impairment or analytical limits are adopted. Drug detection in oral fluid is of interest due to the ease of sampling during roadside controls.

A universal indicator dye pH assay for crystallization solutions and other high-throughput applications.

In protein crystallization, as well as in many other fields, it is known that the pH at which experiments are performed is often the key factor in the success or failure of the trials. With the trend towards plate-based high-throughput experimental techniques, measuring the pH values of solutions one by one becomes prohibitively time- and reagent-expensive. As part of an HT crystallization facility, a colour-based pH assay that is rapid, uses very little reagent and is suitable for 96-well or higher density plates has been developed.

On the need for an international effort to capture, share and use crystallization screening data.

When crystallization screening is conducted many outcomes are observed but typically the only trial recorded in the literature is the condition that yielded the crystal(s) used for subsequent diffraction studies. The initial hit that was optimized and the results of all the other trials are lost. These missing results contain information that would be useful for an improved general understanding of crystallization.

The DINGO dataset: a comprehensive set of data for the SAMPL challenge.

Part of the latest SAMPL challenge was to predict how a small fragment library of 500 commercially available compounds would bind to a protein target. In order to assess the modellers' work, a reasonably comprehensive set of data was collected using a number of techniques. These included surface plasmon resonance, isothermal titration calorimetry, protein crystallization and protein crystallography.

Evaluating the solution from MrBUMP and BALBES.

Molecular replacement is one of the key methods used to solve the problem of determining the phases of structure factors in protein structure solution from X-ray image diffraction data. Its success rate has been steadily improving with the development of improved software methods and the increasing number of structures available in the PDB for use as search models. Despite this, in cases where there is low sequence identity between the target-structure sequence and that of its set of possible homologues it can be a difficult and time-consuming chore to isolate and prepare the best search model for molecular replacement.