Development of a high performance liquid chromatography-tandem mass method for determination of bis(7)-tacrine, a promising anti-Alzheimer's dimer, in rat blood

Hua Yu, Jason M.K. Ho, Kelvin K.W. Kan, Bobby W.H. Cheng, Wen Ming Li, Li Zhang, Ge Lin, Yuan Ping Pang, Zhe Ming Gu, Kelvin Chan, Yi Tao Wang, Yi Fan Han

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

An analytical method using on-line high performance liquid chromatography-tandem mass spectrometry with electrospray ionization was developed and applied for the quantification of bis(7)-tacrine (B7T) in rat blood. B7T and pimozide (internal standard, IS) were extracted in a single step from 100 μl of alkalized blood with ethyl acetate. Analytes were separated using an Extend C-18 column at 25 °C. The elution was achieved isocratically with a mobile phase composed of 0.05% aqueous formic acid and acetonitrile (60:40, v/v) at a flow rate of 0.35 ml/min. Quantification was achieved by monitoring the selected ions at m/z 247 for B7T and m/z 462 → m/z 328 for pimozide. Retention times were 1.45 and 2.23 min for B7T and IS, respectively. Calibration curves were linear in the range from 86.4 to 2160.0 ng/ml. The established method is rapid, selective and sensitive for the identification and quantification of B7T in biological samples. The assay is accurate (bias <10%) and reproducible (intra- and inter-day variation <10%), with detection and quantification limit of 3.6 and 42.3 ng/ml, respectively. Furthermore, it was successfully applied for the pharmacokinetic measurement of B7T in rat with a single intravenous administration at 0.3 mg/kg.

Original languageEnglish (US)
Pages (from-to)1133-1138
Number of pages6
JournalJournal of Pharmaceutical and Biomedical Analysis
Volume44
Issue number5
DOIs
StatePublished - Sep 3 2007

Keywords

  • Alzheimer's disease
  • Bis(7)-tacrine
  • Dimer
  • Drug monitoring
  • HPLC-MS/MS
  • Pharmacokinetics

ASJC Scopus subject areas

  • Analytical Chemistry
  • Pharmaceutical Science
  • Drug Discovery
  • Spectroscopy
  • Clinical Biochemistry

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