Designer benzodiazepines versus prescription benzodiazepines: can structural relation predict the next step?

2021 ◽  
pp. 1-15
Author(s):  
Raneem E. Moustafa ◽  
Fuad Tarbah ◽  
Huda Sulaiman Saeed ◽  
Suleiman I. Sharif
Keyword(s):  
Structural Relation ◽  
Designer Benzodiazepines

scholarly journals Designer Benzodiazepines: A Review of Toxicology and Public Health Risks

2021 ◽  
Vol 14 (6) ◽  
pp. 560
Author(s):  
Pietro Brunetti ◽  
Raffaele Giorgetti ◽  
Adriano Tagliabracci ◽  
Marilyn A. Huestis ◽  
Francesco Paolo Busardò
Keyword(s):  
Public Health ◽  
Adverse Events ◽  
Health Risks ◽  
Drug Market ◽  
Driving Under The Influence ◽  
Self Administration ◽  
Public Health Risks ◽  
Drug Offense ◽  
Legal Sanctions ◽  
Designer Benzodiazepines

The rising use of designer benzodiazepines (DBZD) is a cat-and-mouse game between organized crime and law enforcement. Non-prohibited benzodiazepines are introduced onto the global drug market and scheduled as rapidly as possible by international authorities. In response, DBZD are continuously modified to avoid legal sanctions and drug seizures and generally to increase the abuse potential of the DBZD. This results in an unpredictable fluctuation between the appearance and disappearance of DBZD in the illicit market. Thirty-one DBZD were considered for review after consulting the international early warning database, but only 3-hydroxyphenazepam, adinazolam, clonazolam, etizolam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, meclonazepam, phenazepam and pyrazolam had sufficient data to contribute to this scoping review. A total of 49 reports describing 1 drug offense, 2 self-administration studies, 3 outpatient department admissions, 44 emergency department (ED) admissions, 63 driving under the influence of drugs (DUID) and 141 deaths reported between 2008 and 2021 are included in this study. Etizolam, flualprazolam flubromazolam and phenazepam were implicated in the majority of adverse-events, drug offenses and deaths. However, due to a general lack of knowledge of DBZD pharmacokinetics and toxicity, and due to a lack of validated analytical methods, total cases are much likely higher. Between 2019 and April 2020, DBZD were identified in 48% and 83% of postmortem and DUID cases reported to the UNODC, respectively, with flualprazolam, flubromazolam and etizolam as the most frequently detected substances. DBZD toxicology, public health risks and adverse events are reported.

scholarly journals The Development and Validation of a Novel Designer Benzodiazepines Panel by LC–MS-MS

2021 ◽  
Author(s):  
Rebecca A Mastrovito ◽  
Donna M Papsun ◽  
Barry K Logan
Keyword(s):  
Illicit Drug ◽  
Liquid Extraction ◽  
Electrospray Tandem Mass Spectrometry ◽  
Method Performance ◽  
Internal Standards ◽  
Liquid Liquid Extraction ◽  
Relative Standard ◽  
Development And Validation ◽  
Positive Ion ◽  
Designer Benzodiazepines

Abstract Novel illicit benzodiazepines are among the most active areas of new illicit drug manufacture and use. We describe a method for the detection and quantification of etizolam and its metabolite α-hydroxyetizolam, flubromazolam, clonazolam, diclazepam, delorazepam, bromazepam, flubromazepam, phenazepam, flualprazolam, flunitrazolam, and nitrazolam in human whole blood. After addition of internal standards, samples are buffered and extracted using a liquid–liquid extraction. Analysis is performed using positive-ion electrospray tandem mass spectrometry for detection and quantitation. Calibration ranges were established based on the method performance and differed from compound to compound. Replicates at the lowest calibration point for each compound performed within 5% of CV (Coefficient of Variation). The correlation coefficient was >0.990 for all compounds. Relative standard deviation for all compounds was ≤10% of CV and accuracy was  ±10% for both within- and between-run experiments. The maximum average intra- and inter-run imprecision were 5.7%. The maximum average intra- and inter-run imprecision was −8.7%. As part of evaluating the scope for relevancy, samples testing positive in immunoassay but confirmed to be negative in traditional benzodiazepine confirmation method were re-analyzed using this method. The presence of at least one novel benzodiazepine was identified in 70% of these samples. The appearance of these novel “designer” benzodiazepines demonstrates the challenge for toxicology testing and the need for continually updated confirmation methods.

scholarly journals Complex complementizers and the structural relation with weak T. New (morpho)syntactic data from a Pomeranian language island in Brazil

2014 ◽  
Vol 67 (4) ◽  
Author(s):  
Gertjan Postma
Keyword(s):  
19Th Century ◽  
Head Movement ◽  
Verb Second ◽  
Verbal System ◽  
Espírito Santo ◽  
Structural Relation ◽  
Espirito Santo ◽  
The 19Th Century ◽  
Proper Analysis

AbstractIn this paper I discuss three properties of Brazilian Pomeranian, a Germanic language spoken in Espirito Santo, Brazil by descendents who emigrated in the 19th century. These three aspects of the verbal system are: 1. The relation between complex complementizers, a two-infinitive system, and split infinitives, previously discussed in van Gelderen (1993, 1998) and Schallert (2012, 2013), 2. Verb Projection Raising (VPR), as discussed by Riemsdijk 2002, Haegeman 2007, Salzmann 2011, and Brandner & Salzmann 2012, and 3. Verb-Second positioning of verbal clusters, previously discussed in Vos (2005). I discuss novel Pomeranian data from the perspective of the literature on these three topics, which have been thus far studied largely separately from one another. An integrated discussion sheds light on the nature and the proper analysis of these three phenomena. I argue that these phenomena are caused by the “weaknesses” of T. The weakness of T can be resolved “downward” by copying features onto T under selection by a higher head (agree), or can be resolved “upward” under head movement of T.

Study on the Structural Model of Human Pose

2013 ◽  
Vol 464 ◽  
pp. 387-390
Author(s):  
Wei Hua Wang
Keyword(s):  
Computer Vision ◽  
Human Behavior ◽  
Structural Model ◽  
New Method ◽  
Domain Modeling ◽  
Key Technology ◽  
Broad Application ◽  
Structural Relation ◽  
Human Pose ◽  
Human Image

The analysis and understand of human behavior is broad application in the computer vision domain, modeling the human pose is one of the key technology. In order to simplify the model of the human pose and expediently describe the human pose, a lot of condition was appended to confine the process of human pose modeling or the application environments in the current research. In this paper, a new method for modeling the human pose was proposed. The human pose was modeled by the structural relation according to the physiological structural, the advantages of the model are the independent of move, the independent of scale of the human image and the dependent of view angle, it can be used to modeling the human behavior in video.

Urine Drug Screening in the Era of Designer Benzodiazepines: Comparison of Three Immunoassay Platforms, LC-QTOF-MS, and LC-MS/MS

2021 ◽  
Author(s):  
Andrii Puzyrenko ◽  
Dan Wang ◽  
Randy Schneider ◽  
Greg Wallace ◽  
Sara Schreiber ◽  
...  
Keyword(s):  
Drug Screening ◽  
Forensic Toxicology ◽  
Confirmatory Testing ◽  
Urine Drug ◽  
Screening Assays ◽  
Us Fda ◽  
Urine Specimens ◽  
Abbott Architect ◽  
Designer Benzodiazepines ◽  
Urine Drug Screening

ABSTRACT This study investigated the presence of designer benzodiazepines in 35 urine specimens obtained from emergency department patients undergoing urine drug screening. All specimens showed apparent false-positive benzodiazepine screening results (i.e., confirmatory testing using a 19-component LC-MS/MS panel showed no prescribed benzodiazepines at detectable levels). The primary aims were to identify the possible presence of designer benzodiazepines, characterize the reactivity of commercially available screening immunoassays with designer benzodiazepines, and evaluate the risk of inappropriately ruling out designer benzodiazepine use when utilizing common urine drug screening and confirmatory tests. Specimens were obtained from emergency departments of a single US Health system. Following clinically ordered drug screening using Abbott ARCHITECT c assays and lab-developed LC-MS/MS confirmatory testing, additional characterization was performed for investigative purposes. Specifically, urine specimens were screened using two additional assays (Roche cobas c502, Siemens Dimension Vista) and LC-QTOF-MS to identify presumptively positive species, including benzodiazepines and non-benzodiazepines. Finally, targeted, qualitative LC-MS/MS was performed to confirm the presence of 12 designer benzodiazepines. Following benzodiazepine detection using the Abbott ARCHITECT, benzodiazepines were subsequently detected in 28/35 and 35/35 urine specimens, respectively, using Siemens and Roche assays. LC-QTOF-MS showed the presumptive presence of at least one non-FDA approved benzodiazepine in 30/35 specimens: flubromazolam (12/35), flualprazolam (11/35), flubromazepam (2/35), clonazolam (4/35), etizolam (9/35), metizolam (5/35), nitrazepam (1/35), and pyrazolam (1/35). Two or three designer benzodiazepines were detected concurrently in 13/35 specimens. Qualitative LC-MS/MS confirmed the presence of at least one designer benzodiazepine or metabolite in 23/35 specimens, with 3 specimens unavailable for confirmatory testing. Urine benzodiazepine screening assays from three manufacturers were cross-reactive with multiple non-US FDA-approved benzodiazepines. Clinical and forensic toxicology laboratories using traditionally designed LC-MS/MS panels may fail to confirm the presence of non-US FDA-approved benzodiazepines detected by screening assays, risking inappropriate interpretation of screening results as false-positives.

2. On the Structural relation of Oil and Albumen in the Animal Economy.

1851 ◽  
Vol 2 ◽  
pp. 136-139
Author(s):  
J. H. Bennett
Keyword(s):  
Elementary Cell ◽  
Structural Relation ◽  
Animal Economy ◽  
Vital Functions

Nitrogenised principles of food are subservient to the formation of albumen, whilst the non-nitrogenised are mostly converted into fat or oil. The fact, that a union of these is essential to nutrition, is explained, according to the chemist, by supposing that albumen constitutes the basis of the tissues, and that oil furnishes the elements of respiration and animal heat. This theory, however, does not explain the origin and maintenance of all growth, which is so essential to the vital functions. The author considered that the necessity of oil and albumen was accounted for by their being both necessary to the formation of the tissues, and he endeavoured to shew that there is no elementary cell into which these principles do not enter as constituent parts.

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