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Simple validated method of LC–MS/MS determination of BZ agent in rat plasma samples
- Source :
- Drug Testing and Analysis. 12:431-438
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Agent BZ (3-quinuclidinyl benzilate) is a centrally acting synthetic anticholinergic agent, considered as a potential military incapacitating chemical warfare agent. Despite its significance as a model compound in pharmacological research and its potential misuse in chemical attacks, few modern analytical methods for BZ determination in biological samples have been published. The goal of the present work is to develop and validate a sensitive and rapid LC-MS/MS method for the determination of agent BZ in rat plasma. The sample preparation was based on solid-phase extraction on C-18 cartridges. The reversed-phase HPLC coupled with the mass spectrometer with electrospray ionization in the positive ion-selective reaction monitoring mode was employed in the BZ analysis. Atropine was used as an internal standard. The presented method is selective, accurate, precise, and linear (r2 = 0.9947) in a concentration range from 0.5 ng/mL to 1 000 ng/mL and sensitive enough (limit of detection 0.2 ng/mL; limit of quantification 0.5 ng/mL) to determine the BZ plasma levels in rats exposed to 2 mg/kg and 10 mg/kg of BZ. The highest level of BZ in plasma was observed 5 minutes after intramuscular administration (154.6 ± 22.3 ng/mL in rats exposed to 2 mg/kg of BZ and 1024 ± 269 ng/mL in rats exposed to 10 mg/kg). After 48 h, no BZ was observed at detectable levels. This new method allows the detection and quantification of BZ in biological samples after exposure of an observed organism and it will be further optimized for other tissues to observe the distribution of BZ in organs.
- Subjects :
- Male
Spectrometry, Mass, Electrospray Ionization
3-Quinuclidinyl benzilate
Electrospray ionization
Pharmaceutical Science
Mass spectrometry
01 natural sciences
High-performance liquid chromatography
Cholinergic Antagonists
Analytical Chemistry
03 medical and health sciences
0302 clinical medicine
Limit of Detection
Tandem Mass Spectrometry
Lc ms ms
medicine
Animals
Environmental Chemistry
Sample preparation
030216 legal & forensic medicine
Rats, Wistar
Chromatography, High Pressure Liquid
Spectroscopy
Detection limit
Chromatography
Chemistry
010401 analytical chemistry
Extraction (chemistry)
Rats
0104 chemical sciences
Quinuclidinyl Benzilate
medicine.drug
Subjects
Details
- ISSN :
- 19427611 and 19427603
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Drug Testing and Analysis
- Accession number :
- edsair.doi.dedup.....63e82d9584266e73f7e226f8d0f7b93f