Quantitation of the tacrine analogue octahydroaminoacridine in human plasma by liquid chromatography-tandem mass spectrometry

A rapid and sensitive method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the determination of octahydroaminoacridine in human plasma using tramadol as internal standard (I.S.). Sample preparation involved pH adjustment with sodium carbonate followed by solvent extraction with dichloromethane: ethyl ether (40:60, v/v). Chromatographic separation was achieved on a Venusil MP-C18 column (5 mu m, 100 mm x 4.6 mm) using acetonitrile: 10 MM ammonium acetate:formic acid (30:70:1, v/v/v) as mobile phase. Detection utilized an API 4000 system operated in the positive ion mode with multiple reaction monitoring of the analyte at m/z 203.1 -> 175.1 and of the I.S. at m/z 264.1 -> 58.0. The method was linear in the range 0.01-10ng/ml with a lower limit of quantitation of 0.01 ng/ml. Intra- and inter-day precisions measured as relative standard deviation were <3.15% and <5.01%, respectively. The method was successfully applied to a pharmacokinetic study involving oral administration of a tablet containing 4 mg octahydroaminoacricline succinate to healthy volunteers. Pharmacokinetic parameters for octahydroaminoacricline include C-max 1.19 +/- 0.53 ng/ml, T-max 0.77 +/- 0.17 h, AUC(0-t) 3.42 +/- 1.01 ng h/ml and t(1/2) 2.89 +/- 0.56 h. (C) 2009 Elsevier B.V. All rights reserved.