Selective and sensitive determination of bis(7)‐tacrine, a high erythrocyte binding acetylcholinesterase inhibitor, in rat plasma by high‐performance liquid chromatography–tandem mass spectrometry

Abstract

The current study aims to develop a specific and sensitive LC-MS/MS method for determination of bis(7)-tacrine (B7T) in rat plasma. A 100 microL plasma sample was extracted with ethyl acetate. B7T and the internal standard (IS), pimozide, in the samples were then analyzed with LC-MS/MS in positive electrospray ionization condition. Chromatographic separation of B7T and IS was achieved in a C(18) reversed-phase HPLC column (150 x 2.1 mm i.d.) by isocratic elution with a mobile phase consisting of 0.05% formic acid in water and acetonitrile (1:1, v/v) at a flow rate of 0.35 mL/min. Multiple-reaction monitoring (MRM) mode was employed to measure the ion transitions: m/z 247 to 197 for B7T and m/z 462 to m/z 328 for IS, respectively. The method was linear over the studied ranges of 100-5000 and 10-100 ng/mL. The intra-day and inter-day variations of the analysis were less than 6.8% with standard errors less than 9.0%. The detection limit of B7T in rat plasma was 1 ng/mL. The developed method was successfully applied to the pharmacokinetic study of B7T after intravenous administration of 1 mg/kg B7T and further proved to be readily utilized for determination of B7T in rat plasma samples.

Neuroprotective effects of bis(7)-tacrine against glutamate-induced retinal ganglion cells damage

“…The pharmacokinetic research in the body of the rat showed that bis(7)-tacrine was rapidly and widely distributed to its target tissues such as brain[41,42]. In a model of acute focal cerebral ischemic insults in MCAO rats, bis(7)-tacrine at doses of 0.1 mg/kg and 0.2 mg/kg significantly reduced ischemic impairment in vivo[23].…”

Quantification of Amiridine in Human Plasma by High-Performance Liquid Chromatography Coupled with Electrospray Tandem Mass Spectrometry

“…LC/MS spectrometry based techniques are now the mainstay for such pharmacokinetic studies because of sensitivity, selectivity, speed, and cost effectiveness [9]. HPLC-MS/MS method for quantification of tacrine in biological samples has been developed [10]. However, we do not find HPLC-MS/MS methods reported in the literature for quantification of amiridine in biological samples.…”