Fluorometric determination of an inverse agonist to benzodiazepine receptors S-135 in monkey plasma by high performance liquid chromatography.
A high performance liquid chromatographic method for the determination of an agent of benzodiazepine receptor inverse agonist (S-135) was developed. S-135 in monkey plasma, after its administration, was assayed using the method. S-135 is ionized in alkaline N,N-dimethylformamide (DMF), and fluoresces strongly at 490 nm on excitation at 290 nm. Extracted S-135 from a plasma sample was separated with an Asahipak GS-310H polyvinyl alcohol gel column and detected fluorometrically, with the eluate being mixed with a triethylamine-DMF mixture. S-135 in plasma is assayable with a coefficient of variation being less than 3.5% (n = 11). The lower limit of the determination is 2 ng/ml. This method was applied as a highly sensitive and simple method to pharmacokinetic studies of S-135 after oral administration to cynomolgus monkeys.
Ikenishi
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Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Kitagawa
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D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004126:Dimethylformamide / Q000737:chemistry; D008252:Macaca fascicularis; D011720:Pyrazoles / Q000097:blood* / Q000494:pharmacology; D015363:Quinolones / Q000097:blood* / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000187:drug effects*; D013050:Spectrometry, Fluorescence
D011720:Pyrazoles; D015363:Quinolones; D011963:Receptors, GABA-A; C059074:S 135; D004126:Dimethylformamide