Nazolam (midazolam intranasal spray) / MEDIR - LARVOL DELTA

An analytical strategy for designer benzodiazepines and Z-hypnotics determination in plasma samples using ultra-high performance liquid chromatography/tandem mass spectrometry after microextraction by packed sorbent. (PubMed, J Pharm Biomed Anal) - "In this work, a procedure based on microextraction by packed sorbent (MEPS) in combination with ultra-high performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) has been developed to determine the designer benzodiazepines (clonazolam, deschloroetizolam, nifoxipam, flubromazolam and meclonazepam), and the Z-hypnotics (zolpidem, zaleplon and zopiclone) in plasma. Intra and interday precision expressed as relative standard deviations, were < 10.6 % and process efficiency ranged from 63 to 117 % for the quality control samples. The proposed method detected zolpidem and various other benzodiazepines in plasma samples from overdoses cases."

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Clarification Of The Correct Nomenclature Of The Amino Metabolite Of Clonazolam: 8-Aminoclonazolam. (PubMed, J Anal Toxicol) - No abstract available

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Development and Validation of an LC-MS-MS Method for the Detection of 40 Benzodiazepines and Three Z-Drugs in Blood and Urine by Solid-Phase Extraction. (PubMed, J Anal Toxicol) - "An analytical method for the detection of 40 benzodiazepines, (±)-zopiclone, zaleplon and zolpidem in blood and urine by solid-phase extraction liquid chromatography-tandem mass spectrometry was developed and validated...Bias and between-and within-day imprecision for quality controls (QCs) were all within ±15%, except for clonazolam and etizolam that were within ±20%...The ability to analyze quantitative blood and qualitative urine samples in the same batch is one of the most useful elements of this procedure. This sensitive, specific and robust analytical method was routinely employed in the analysis of >300 samples in our laboratory over the last 6 months."

Journal

Newly Emerging Drugs of Abuse. (PubMed, Handb Exp Pharmacol) - "In this review, epidemiology, chemistry, pharmacophysiology, clinical effects, laboratory detection, and clinical treatment are discussed for newly emerging drugs of abuse in the following classes: (1) opioids (e.g., fentanyl, fentanyl analogues, and mitragynine), (2) cannabinoids [THC and its analogues, alkylindole (e.g., JWH-018, JWH-073), cyclohexylphenol (e.g., CP-47,497), and indazole carboxamide (e.g., FUB-AMB, ADB-FUBINACA)], (3) stimulants and hallucinogens [β-keto amphetamines (e.g., methcathinone, methylone), pyrrolidinophenones (e.g., α-PVP, MDPV), and dimethoxyphenethylamine ("2C" and "NBOMe")], (4) dissociative agents (e.g., 3-MeO-PCP, methoxetamine, 2-oxo-PCE), and (5) sedative-hypnotics (e.g., gabapentin, baclofen, clonazolam, etizolam). It is critically important to coordinate hospital, medical examiner, and law enforcement personnel with laboratory services to respond to these emerging threats."

Journal • Addiction (Opioid and Alcohol)

Blood concentrations of designer benzodiazepines: Relation to impairment and findings in forensic cases. (PubMed, J Anal Toxicol) - "The aim of this study was to report blood concentrations of clonazolam, diclazepam, etizolam, flualprazolam, flubromazepam, flubromazolam and phenazepam, and to investigate the relationship between blood concentrations and impairment...The most frequent other drugs detected were amphetamine, tetrahydrocannabinol, clonazepam and methamphetamine. The presented blood concentrations can be helpful with the interpretation of cases involving one or more of these seven benzodiazepines. The results indicate that concentrations commonly observed in forensic cases are associated with impairment."

Clinical • Journal

Pathogen identification in 84 Patients with post-traumatic osteomyelitis after limb fractures. (PubMed, Ann Palliat Med) - "The incidence of PTO in the Zunyi area is similar to the national level. The most common site of infection is the lower extremity. Bacterial infections (mainly infection caused by a single bacterial type) were observed in 77.8% of the cases. Staphylococcus aureus is the most common pathogenic bacteria, followed by Escherichia coli and Enterobacter cloacae. The antibiotic-resistant bacteria have characteristic distributions in different regions."

Clinical • Journal

Detailed quantum mechanical studies on bioactive benzodiazepine derivatives and their adsorption over graphene sheets. (PubMed, Spectrochim Acta A Mol Biomol Spectrosc) - "Estazolam (Z1) and related derivatives, adinazolam (Z2), alprazolam (Z3), 4-hydroxyalprazolam (Z4) and triazolam (Z5) have been studied by using various computational tools to analyze their geometry and spectral characteristics. It can be seen that the highest interaction energy has been obtained in the case of the Z5-graphene system, while the lowest interaction energy has been obtained in the case of the Z1-graphene system. Docking indicates that the ligands adsorbed over graphene also form stable complexes with the receptors as indicated by the high binding affinity energy values."

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Validation of an LC-MS/MS Method for the Quantification of 13 Designer Benzodiazepines in Blood. (PubMed, J Anal Toxicol) - "The developed method included 3-hydroxyphenazepam, clobazam, clonazolam, delorazepam, deschloroetizolam, diclazepam, flualprazolam, flubromazepam, flubromazolam, flunitrazolam, meclonazepam, nifoxipam and pyrazolam in 0.5 mL postmortem blood using liquid chromatography-tandem mass spectrometry. Other parameters tested included carryover, stability, interference and dilution integrity, which all yielded acceptable results. With the application of this method to blood specimens from the New York City Office of Chief Medical Examiner, this validated method proved to be simple, reproducible, sensitive and robust."

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Designer benzodiazepines: a report of exposures recorded in the National Poison Data System, 2014-2017. (PubMed, Clin Toxicol (Phila)) - "The incidence of exposures to designer benzodiazepines is rising. Clinical effects are generally consistent with a sedative-hypnotic toxidrome. Severe effects, including death, seemed relatively uncommon in the study population."

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Designer benzodiazepines' pharmacological effects and potencies: How to find the information. (PubMed, J Psychopharmacol) - "In total, 197 TRs for clonazolam, deschloroetizolam, diclazepam, etizolam, flubromazepam, flubromazolam, meclonazepam, metizolam, nifoxipam and pyrazolam were analyzed. The chemical structure of the different DBZDs and the functional groups on the BZD rings confirmed this ranking, except for nifoxipam. When information on NPSs obtained from Internet fora are abundant, it could be considered as an appreciable data source."

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Occurrence and time course of NPS benzodiazepines in Sweden - results from intoxication cases in the STRIDA project. (PubMed, Clin Toxicol (Phila)) - "An increasing use of NPS BZD in Sweden was detected in acute intoxication cases, sometimes leading to intensive care monitoring and support needs."

Clinical • Journal

A Liquid-Chromatography High-Resolution Mass Spectrometry Method for Non-FDA Approved Benzodiazepines. (PubMed, J Anal Toxicol) - "In a clinical research case, clonazolam and etizolam were detected in serum at 10.2 and 281 ng/mL, with an apparent elimination half-life of 3.6 and 4.8 hours, respectively. Although we did not detect non-FDA approved BZDs in 211 urine samples that were previously determined to be BZD-positive by immunoassay, abuse of these drugs is on the rise and clinical and forensic toxicology laboratories should consider developing methods to detect them."

FDA event • Journal

Designer Benzodiazepines: Another Class of New Psychoactive Substances. (PubMed, Handb Exp Pharmacol) - "As they were obviously designed to circumvent national narcotics laws or international control, they can be referred to as "designer benzodiazepines." The majority of these compounds, such as diclazepam, clonazolam, and nitrazolam, have been described in scientific or patent literature. However, little is known about their pharmacological properties and specific risks related to their use. This chapter describes the phenomenon of designer benzodiazepines and summarizes the available data on pharmacokinetics and pharmacodynamics as well as analytical approaches for their detection."

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Systemic Disseminated Mycobacterium Fortuitum Infection in an Immunocompetent Patient: A Case Report and Literature Review (ATS 2019) - "After clarithromycin + levofloxacin + linazolamide treatment for 3 months, the lung lesions, papules and erythema on face were all improved and she had no fever or other additional complication.Discussion Systemic disseminated Mycobacterium fortuitum infection is rare in healthy adult, and patients with GATA2 deletion and IFN-γ autoantibodies may be a potential mechanism. We emphasize the importance of tissue biopsy and culture of this pathogen in order to facilitate accurate diagnosis and appropriate treatment. Key words: Mycobacterium fortuitum;Disseminated infection"

Clinical

The Mystery Chemical: A Case of Designer Benzodiazepine Intoxication Resulting in Hyperactive Delirium (APA 2019) - "During his second hospitalization, he revealed that he had purchased clonazolam, a highpotency “research chemical” benzodiazepine, over the internet, and that it had been shipped to him from a domestic location. Providers should consider screening for these types of substances as part of their substance use history, especially in patients at high risk. This case highlights an alarming trend and potentially unanticipated consequence of more restrictive prescribing practices and may represent a coming phase in the management of substance use disorders."

Clinical

In vitro glucuronidation of designer benzodiazepines by human UDP-glucuronyltransferases. (PubMed, Drug Test Anal) - "Clonazolam, deschloroetizolam, etizolam, flubromazolam, flunitrazolam, metizolam, nifoxipam, nitrazolam, and pyrazolam were incubated with pooled human liver microsomes (pHLM) or 13 different human UGTs. The conjugation of the majority of the DBZ was performed by the UGT isoform 1A4 for which polymorphisms have been described. This underlines the importance of taking glucuronidation polymorphism into consideration when interpreting intoxication cases."

Journal • Preclinical