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Development of a high performance liquid chromatography-tandem mass method for determination of bis(7)-tactrine, a promising anti-Alzheimer's dimer, in rat blood
Journal of Pharmaceutical and Biomedical Analysis (2007)
  • Kelvin Chan
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 l 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.

Keywords
  • Bis(7)-tactrine,
  • Dimer,
  • Alzheimer's Disease,
  • HPLC-MS/MS,
  • Drug monitoring,
  • Pharmacokinetics
Disciplines
Publication Date
2007
Citation Information
Kelvin Chan. "Development of a high performance liquid chromatography-tandem mass method for determination of bis(7)-tactrine, a promising anti-Alzheimer's dimer, in rat blood" Journal of Pharmaceutical and Biomedical Analysis Vol. 44 (2007)
Available at: http://works.bepress.com/kelvin_chan/15/