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

Abstract

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 min⁻¹. The lower limit of quantitation of the developed method was found to be 2.0 ng mL⁻¹ and 5.0 ng g⁻¹ for plasma and tissue samples, respectively. Following intraperitoneal (i.p.) administration, BQCA was remarkably absorbed into the systemic circulation with maximum concentration (∼8000.0 ng mL⁻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 3–4 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 kg⁻¹.