Determination of tacrine-6-ferulic acid in rat plasma by LC-MS/MS and its application to pharmacokinetics study.
Tacrine, as a drug for treating Alzheimer's disease (AD), has low efficacy owing to its single function and serious side effects. However, tacrine-6-ferulic acid (T6FA), the dimer which added ferulic acid to tacrine, has been found to be a promising multifunctional drug candidate for AD and much more potent and selective on acetylcholinesterase (AChE) than tacrine. The aim of the present work was to develop and validate an LC-MS/MS method with electrospray ionization for the quantification of T6FA in rat plasma using tacrine-3-ferulic acid (T3FA) as internal standard and to examine its application for pharmacokinetic study in rats. Following a single liquid-liquid extraction with ethyl acetate, chromatographic separation was achieved at 25 °C on a BDS Hypersil C18 column with a mobile phase composed of 1% formic acid and methonal (30:70, v/v) at a flow rate of 0.2 mL/min. Quantification was achieved by monitoring the selected ions at m/z 474.2 → 298.1 for T6FA and m/z 432.2 → 199.0 for T3FA. The method was validated to be rapid, specific, accurate and precise over the concentration range of 0.5-1000.0 ng/mL in rat samples. Furthermore, it was successfully applied for the pharmacokinetic measurement of T6FA with an oral administration at 40 mg/kg to rats.
School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
Xiuman
X
Sun
Peiting
P
Zhang
Rongbiao
R
Pi
Yuting
Y
Zhou
Xuejiao
X
Deng
Zhiyong
Z
Xie
Qiongfeng
Q
Liao
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003373:Coumaric Acids / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D004355:Drug Stability; D016014:Linear Models; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013619:Tacrine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D053719:Tandem Mass Spectrometry / Q000379:methods*
D003373:Coumaric Acids; C574537:tacrine-6-ferulic acid; D013619:Tacrine
LC-MS/MS; pharmacokinetic study; tacrine-6-ferulic acid (T6FA)