Abstract
Ailanthone, a natural compound isolated from Chinese herb Ailanthus altissima, has drawn a lot of attention for its antitumor activity. In this study, a simple and sensitive method for determination of ailanthone in rat plasma was developed for the first time, using high-performance liquid chromatography–tandem mass spectrometry (LC–MS/MS). Brusatol was used as an internal standard. Separation was achieved on an Agilent Zorbax Eclipse Plus C18 column with gradient elution using water–methanol as mobile phase at a flow rate of 0.2mL/min. A triple quadrupole mass spectrometer operating in the negative electrospray ionization mode with multiple reaction monitoring (MRM) was used to detect ailanthone and IS transitions of 375.2→301.1 and 519.1→437.4, respectively. The lower limit of quantification was 5ng/mL with a linear range of 5–2000ng/mL. The intra- and inter-day accuracy (RE) ranged from −3.6 to 1.5% and −0.7 to 4.7% and the intra- and inter-day precision (RSD) was between 2.8–6.7% and 3.1–8.0%. The validated method has been successfully applied to a pharmacokinetic study of ailanthone in rats. The elimination half-lives (t1/2) were 105.5±13.6, 113.3±39.6, and 95.8±23.9min after single intravenous administration of 0.5, 1.0, and 1.5mg/kg ailanthone, respectively. The area under the plasma concentration versus time curve (AUC0–6h) and initial plasma concentration (C0) were linearly related to dose.
Published Version
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