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.
Zhang
Li
L
Department of Biochemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, SAR, People's Republic of China.
Li
Zhang
Z
Yu
Hua
H
Hua
Yu
Y
Li
Wen Ming
WM
Ming
Li Wen
LW
Cheung
Man Chun
MC
Chun
Cheung Man
CM
Pang
Yuan Ping
YP
Ping
Pang Yuan
PY
Lin
Ge
G
Ge
Lin
L
Wang
Yi Tao
YT
Tao
Wang Yi
WY
Zuo
Zhong
Z
Zhong
Zuo
Z
Han
Yi Fan
YF
Fan
Han Yi
HY
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