Pharmacokinetics and tissue distribution of a M1 muscarinic acetylcholine receptor positive allosteric potentiator, benzyl quinolone carboxylic acid

摘要

A simple, sensitive and selective high performance liquid chromatography method has been developed and validated for the estimation of benzyl quinolone carboxylic acid (BQCA) in Sprague-Dawley (SD) rat plasma and tissue samples. Plasma and tissue samples were extracted by a protein precipitation technique using methanol as a precipitating agent and donepezil as the internal standard. Chromatographic separation was performed on a Hibar C18 column with a mobile phase of acetonitrile and potassium dihydrogen orthophosphate buffer (20 mM, pH 6.5) at a flow rate of 0.8 mL mina?’1. The lower limit of quantitation of the developed method was found to be 2.0 ng mLa?’1 and 5.0 ng ga?’1 for plasma and tissue samples, respectively. Following intraperitoneal (i.p.) administration, BQCA was remarkably absorbed into the systemic circulation with maximum concentration (a??8000.0 ng mLa?’1) within 1.5 h. The order of the area under the curve results from the tissue distribution study was kidney lung liver brain spleen heart. BQCA was rapidly taken up into the brain resulting in a maximal brain concentration after 1.5 h which was maintained for up to 3a€“4 h. The method was successfully applied in the analysis of BQCA in plasma and tissue samples following i.p. administration to SD rats at a dose of 10 mg kga?’1.