title: Development of a validated LC-MS/MS method for the determination of ailanthone in rat plasma with application to pharmacokinetic study.
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 0.2 mL/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 5 ng/mL with a linear range of 5-2000 ng/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 ± 23.9 min 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.
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Ang
authors.initials: A
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Qin
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China.
authors.forename: Zhengfang
authors.initials: Z
authors.lastname: Yi
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China; Center for Cancer and Stem Cell Biology, Institute of Biosciences and Technology, Texas A&M University Health Science Center, Houston, TX, USA.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Liu
authors.affiliation: Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, China. Electronic address: usxinwang@gmail.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods / Q000592:standards; D013058:Mass Spectrometry / Q000379:methods / Q000592:standards; D036702:Quassins / Q000097:blood* / Q000493:pharmacokinetics; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods / Q000592:standards*
chemical_list: D036702:Quassins; C029825:ailanthone
keywords: Ailanthone; In vivo; LC–MS/MS; Pharmacokinetics; Rat plasma