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.
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.
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, SAR, People's Republic of China.
Li
L
Zhang
Zhang
Z
Li
Hua
H
Yu
Yu
Y
Hua
Wen Ming
WM
Li
Li Wen
LW
Ming
Man Chun
MC
Cheung
Cheung Man
CM
Chun
Yuan Ping
YP
Pang
Pang Yuan
PY
Ping
Ge
G
Lin
Lin
L
Ge
Yi Tao
YT
Wang
Wang Yi
WY
Tao
Zhong
Z
Zuo
Zuo
Z
Zhong
Yi Fan
YF
Han
Han Yi
HY
Fan
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004912:Erythrocytes / Q000378:metabolism*; D015394:Molecular Structure; D051381:Rats; D015203:Reproducibility of Results; D013619:Tacrine / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*
D002800:Cholinesterase Inhibitors; D013619:Tacrine