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.
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 microl of alkalized blood with ethyl acetate. Analytes were separated using an Extend C-18 column at 25 degrees 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 0.3mg/kg.
Yu
Hua
H
Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, SAR, PR China.
Ho
Jason M K
JM
Kan
Kelvin K W
KK
Cheng
Bobby W H
BW
Li
Wen-Ming
WM
Zhang
Li
L
Lin
Ge
G
Pang
Yuan-Ping
YP
Gu
Zhe-Ming
ZM
Chan
Kelvin
K
Wang
Yi-Tao
YT
Han
Yi-Fan
YF
D000544:Alzheimer Disease / Q000188:drug therapy*; D000818:Animals; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005615:Freezing; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D015394:Molecular Structure; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013619:Tacrine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors
C122128:1,7-N-heptylene-bis-9,9'-amino-1,2,3,4-tetrahydroacridine; D013619:Tacrine