Abstract |
An highly sensitive and fully automated high-performance liquid chromatographic assay was developed for the determination of a novel non- benzodiazepine anxiolytic (I) [(R)-2-(methoxymethyl)-1-[(7-oxo-8-phenyl-7H-thieno[2,3-a]quinolizin+ ++- 10-yl)carbonyl] pyrrolidine] and its O-demethyl metabolite (II) in plasma, using column-switching for direct injection of plasma samples. After dilution in internal standard solution, the sample was injected onto a pre-column (17 mm x 4.6 mm) dry-packed with pellicular C18 reversed-phase material. Polar plasma components were removed by flushing the pre-column with water- acetonitrile (90:10, v/v). Retained substances, including I and II, were backflushed onto an analytical column, separated by gradient elution and detected by means of fluorescence detection (excitation, 304 nm; emission, 475 nm). After washing the analytical column and re-equilibrating the pre-column, the system was ready for the next injection. The limit of quantification for I and II was 0.25 and 0.5 ng/ml, respectively, using a 350-microliter specimen of plasma. The practicability of the new method was demonstrated by analysis of more than 300 plasma samples from a tolerance study performed with human volunteers. Owing to its high sensitivity, the method can be used to calculate pharmacokinetic parameters of compounds I and II in man after a single oral dose of about 1 mg of I.
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Authors | U Timm, G Hopfgartner, R Erdin |
Journal | Journal of chromatography
(J Chromatogr)
Vol. 456
Issue 1
Pg. 21-31
(Dec 02 1988)
Netherlands |
PMID | 2907518
(Publication Type: Journal Article)
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Chemical References |
- Anti-Anxiety Agents
- Pyrrolidines
- Quinolizines
- 2-(hydroxymethyl)-1-((7-oxo-8-phenyl-7H-thieno(2,3-a)quinolizin-10-yl)carbonyl)pyrrolidine
- Ro 195686
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Topics |
- Anti-Anxiety Agents
(blood)
- Chemical Phenomena
- Chemistry
- Chromatography, High Pressure Liquid
- Humans
- Pyrrolidines
(blood, metabolism)
- Quinolizines
(blood, metabolism)
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