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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.
Yu, Hua Ho, Jason Kan, Kelvin K. Cheng, Bobby Li, Wen-Ming Zhang, Li Lin, Ge Pang, Yuan-Ping Gu, Zhe-Ming Chan, Kelvin C.
Yu, Hua
Ho, Jason
Kan, Kelvin K.
Cheng, Bobby
Li, Wen-Ming
Zhang, Li
Lin, Ge
Pang, Yuan-Ping
Gu, Zhe-Ming
Chan, Kelvin C.
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Other contributors
Affiliation
Epub Date
Issue Date
2007
Submitted date
Subjects
Alternative
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 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.
Citation
Journal of pharmaceutical and biomedical analysis, 44(5): 1133-1188
Publisher
Research Unit
PubMed ID
17628383
PubMed Central ID
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Type
Journal article
Language
en
Description
Series/Report no.
ISSN
0731-7085