3-Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non-lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats. Moreover, BZ can be exploited to produce a pharmacological model of Alzheimer's disease; thus, this paper focuses mainly on the BZ distribution to the brain. Wistar rats were administered i.p. with BZ (2 and 10 mg/kg). The BZ concentration was determined using LC-MS/MS in plasma, urine, bile, brain, kidney and liver. The sample preparation was based on a solid phase extraction (liquids) or protein precipitation (organ homogenates). The plasma concentration peaked at 3 min (204.5 ± 55.4 and 2185.5 ± 465.4 ng/ml). The maximal concentration in the brain was reached several minutes later. Plasma elimination half-life was 67.9 ± 3.4 in the 2 mg/kg group and 96.6 ± 27.9 in the 10 mg/kg group. BZ concentrations remained steady in the brain, with slow elimination (t 506.9 ± 359.5 min). Agent BZ is excreted mainly via the urine. Steady BZ concentration in the brain could explain the previously published duration of the significant impairment in passive avoidance tasks in rats after an injection of BZ.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1111/bcpt.13627 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Development of simultaneous determination of dopamine 2, histamine 1, and muscarinic acetylcholine receptor occupancies by antipsychotics using liquid chromatography with tandem mass spectrometry.
J Pharmacol Toxicol Methods
June 2024
Laboratory of Pharmaceutics, Faculty of Pharmaceutical Sciences, Teikyo University, Tokyo, Japan. Electronic address:
Receptor occupancy is an indicator of antipsychotic efficacy and safety. It is desirable to simultaneously determine the occupancy of multiple brain receptors as an indicator of the efficacy and central side effects of antipsychotics because many of these drugs have binding affinities for various receptors, such as dopamine 2 (D), histamine 1 (H), and muscarinic acetylcholine (mACh) receptors. The purpose of this study was to develop a method for the simultaneous measurement of multiple receptor occupancies in the brain by the simultaneous quantification of unlabeled tracer levels using liquid chromatography-tandem mass spectrometry (LC-MS/MS).
View Article and Find Full Text PDFIncapacitating agents review: 20 years after Nord Ost Siege.
Crit Rev Toxicol
September 2023
National Poison Center, Prof. Alejandro Posadas National Hospital, Buenos Aires, Argentina.
Incapacitating agents are chemical weapons that produce a temporary disabling condition that persists for hours or days after exposure. Their main site of action is the central nervous system and includes substances that are considered depressants or stimulants. While not intended to cause death, can produce significant morbidity in affected patients.
View Article and Find Full Text PDFSimultaneous solvent extraction and quantification of eleven amine compounds related to Chemical Weapon Convention in soils via hydrophilic interaction liquid chromatography-tandem mass spectrometry.
J Chromatogr A
May 2022
State Key Laboratory of NBC Protection for Civilian, Beijing 102205, China; Laboratory of Analytical Chemistry, Research Institute of Chemical Defence, Beijing 102205, China. Electronic address:
The detection of Chemical Weapon Convention (CWC)-related amine compounds including the precursors or degradation products of V-type organophosphorus nerve agent, nitrogen mustard and 3-quinuclidinyl benzilate is an important aspect for verifying their intact chemical warfare agents. This work focuses on the development of a novel formulation for the simultaneous solvent extraction of eleven CWC-related amine compounds, from the four-type soil matrices including environmental standard soil, sand, clay, and loam. Extracts were well separated on the hydrophilic interaction liquid chromatography (HILIC) and then detected by MS/MS multiple reaction monitoring mode.
View Article and Find Full Text PDF3-Quinuclidinyl benzilate (agent BZ) toxicokinetics in rats.
Basic Clin Pharmacol Toxicol
September 2021
Department of Toxicology and Military Pharmacy, Faculty of Military Health Sciences in Hradec Kralove, University of Defence, Brno, Czech Republic.
3-Quinuclidinyl benzilate (BZ) ranks among incapacitating military warfare agents. It acts as a competitive inhibitor on muscarinic receptors leading to non-lethal mental impairment. The present study aimed to investigate toxicokinetics of BZ in rats.
View Article and Find Full Text PDFTrocylation of 3-quinuclidinol, a key marker for the chemical warfare agent 3-quinuclidinyl benzilate, for its enhanced detection at low levels in complex soil matrices by electron ionization gas chromatography-mass spectrometry.
Rapid Commun Mass Spectrom
August 2021
Physical and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, CA, 94550, USA.
Rationale: Detection of 3-quinuclidinol (3Q), a marker for the chemical warfare agent 3-quinuclidinyl benzilate, is very difficult by gas chromatography-mass spectrometry (GC/MS), providing low, broad signals even when analyzed in isolated form. Therefore, a method that can convert 3Q into a substrate with enhanced detectability by GC/MS would be an important tool for its analysis.
Methods: 2,2,2-Trichloroethoxycarbonyl chloride (TrocCl) was used in the derivatization of 3Q in three different soils of varying composition and total organic content (Virginia type A soil, Nebraska EPA standard soil and Ottawa sand) when present at a 10 μg g concentration in each.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!