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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
Author(s) -
Li Zhang,
Hua Yu,
Ming Li Wen,
Chun Cheung Man,
Ping Pang Yuan,
Ge Lin,
Tao Wang Yi,
Zhong Zuo,
Fan Han Yi
Publication year - 2008
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.949
Subject(s) - tacrine , chemistry , chromatography , tandem mass spectrometry , acetylcholinesterase , mass spectrometry , liquid chromatography–mass spectrometry , tandem , acetylcholinesterase inhibitor , high performance liquid chromatography , cholinesterase , enzyme , biochemistry , pharmacology , medicine , materials science , composite material
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 µL 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 × 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. Copyright © 2007 John Wiley & Sons, Ltd.