Hansen_1998_J.Chromatogr.B.Biomed.Sci.Appl_712_183

A new method for the simultaneous quantitation of tacrine and the three metabolites, 1-hydroxytacrine (velnacrine, maleate), 2-hydroxytacrine and 4-hydroxytacrine, in human plasma and urine has been developed. The method was based on simple one-step liquid-liquid extraction with ethyl acetate followed by isocratic, reversed-phase high-performance liquid chromatography and fluorescence detection (excitation: 330 nm and emission: 365 nm). The limit of detection in plasma was 0.5 nM for 2-hydroxytacrine and 4-hydroxytacrine, 2 nM for 1-hydroxytacrine and tacrine. In urine it was 60 nM for 2-hydroxytacrine and 4-hydroxytacrine, 30 nM for 1-hydroxytacrine and 80 nM for tacrine. The limit of quantification in plasma was 2.5 nM for 2-hydroxytacrine and 4-hydroxytacrine, 10 nM for 1-hydroxytacrine and 2 nM for tacrine. In urine it was 120 nM for all components. The overall mean recoveries ranged from 84 to 105% in plasma and from 64 to 100% in urine for all four compounds.