Title: Quantitation of the Ultra Short Acting β-Adrenergic Antagonist Flestolol in Blood by Liquid Chromatography
Abstract: A sensitive, specific, reproducible, and convenient high-performance liquid chromatographic (HPLC) assay was developed for quantitation of the new ultra short acting beta-adrenergic antagonist, flestolol (1), in whole blood. The instability of the compound in blood was overcome by the esterase inhibitor, NaF, and deproteinization of blood samples with CH3CN:CH2Cl2 (2:5). The internal standard was p-ethoxyphenethyl alcohol. The compounds were back extracted from the CH3CN:CH2Cl2 phase into a small volume of pH 3-4 phosphate buffer and then separated on a reversed-phase C18 column with 0.05 M phosphate buffer (pH 3-4) in acetonitrile (4.6:1) as the mobile phase, and detected with an UV detector at 229 nm. The assay was linear with a blood concentration range from 10 to 1270 ng/mL (r2 greater than 0.998, p greater than 0.01), and reproducible with an overall CV of 8%. The assay procedure was used to determine the blood levels of flestolol intravenously infused into a male dog for 105 min at 230 micrograms/kg/min. The steady-state unchanged drug concentration of 5 micrograms/mL in blood was achieved within 10-20 min and declined biexponentially to 0.02 microgram/mL at 6 h following termination of the infusion.
Publication Year: 1986
Publication Date: 1986-04-01
Language: en
Type: article
Indexed In: ['crossref', 'pubmed']
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Cited By Count: 3
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