Abstract |
This study describes a chromatographic method for the determination of diazepam, an anxiolytic drug that is also used as an antidote against nerve agent seizures, its metabolites N- desmethyldiazepam, and temazepam, the anti- nerve agent drug pyridostigmine bromide (PB; 3-dimethylaminocarbonyloxy-N-methyl pyridinium bromide) and its metabolite N-methyl-3-hydroxypyridinium bromide in rat plasma and urine. The compounds were extracted using C18 Sep-Pak Vac 3cc (500 mg) cartridges and separated using isocratic mobile phase of methanol, acetonitrile and water (pH 3.2) (10:40:50) at a flow-rate of 0.5 ml/min in a period of 12 min, and UV detection ranging between 240 and 280 nm. The limits of detection for all analytes ranged between 20 and 50 ng/ml, while limits of quantitation were 100 ng/ml. Average percentage extraction recoveries of five spiked plasma samples were 79.1+/-7.7, 83.5+/-6.4, 83.9+/-5.9, 71.3+/-6.0 and 77.7+/-5.6, and from urine 79.4+/-7.9, 83.1+/-6.9, 73.6+/-7.7, 74.3+/-7.1 and 77.6+/-5.9 for diazepam, N- desmethyldiazepam, temazepam, pyridostigmine bromide, and N-methyl-3-hydroxypyridinium bromide, respectively. The relationship between peak areas and concentration was linear over the range between 100 and 1000 ng/ml. This method was applied to determine the above analytes following a single oral administration in rats as a tool to study the pharmacokinetic profile of each compound, alone and in combination.
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Authors | A W Abu-Qare, M B Abou-Donia |
Journal | Journal of chromatography. B, Biomedical sciences and applications
(J Chromatogr B Biomed Sci Appl)
Vol. 754
Issue 2
Pg. 503-9
(Apr 25 2001)
ISSN: 1387-2273 [Print] Netherlands |
PMID | 11339294
(Publication Type: Journal Article)
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Chemical References |
- Anti-Anxiety Agents
- Cholinesterase Inhibitors
- Pyridostigmine Bromide
- Diazepam
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Topics |
- Animals
- Anti-Anxiety Agents
(analysis, blood, metabolism, urine)
- Calibration
- Cholinesterase Inhibitors
(analysis, blood, metabolism, urine)
- Chromatography, High Pressure Liquid
(methods)
- Diazepam
(analysis, blood, metabolism, urine)
- Pyridostigmine Bromide
(analysis, blood, metabolism, urine)
- Quality Control
- Rats
- Rats, Sprague-Dawley
- Reference Standards
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