title: Quantitation of the tacrine analogue octahydroaminoacridine in human plasma by liquid chromatography-tandem mass spectrometry.
abstract: 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 microm, 100 mm x 4.6mm) using acetonitrile:10mM 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 0.01-10 ng/ml with a lower limit of quantitation of 0.0 1ng/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 octahydroaminoacridine succinate to healthy volunteers. Pharmacokinetic parameters for octahydroaminoacridine 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.
authors.affiliation: Research Center for Drug Metabolism, College of Life Science, Jilin University, Changchun 130021, PR China.
authors.forename: Jiangbin
authors.initials: J
authors.lastname: Han
authors.forename: Shuang
authors.initials: S
authors.lastname: Jiang
authors.forename: Xiangyong
authors.initials: X
authors.lastname: Cui
authors.forename: Yantong
authors.initials: Y
authors.lastname: Sun
authors.forename: Guoqing
authors.initials: G
authors.lastname: Li
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zhang
authors.forename: J Paul
authors.initials: JP
authors.lastname: Fawcett
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
mesh_terms: D000585:Aminacrine / Q000031:analogs & derivatives* / Q000032:analysis; D002853:Chromatography, Liquid / Q000379:methods*; D006801:Humans; D012015:Reference Standards; D012016:Reference Values; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C543173:octahydroaminoacridine; D000585:Aminacrine