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Pharmacokinetics and Tissue Distribution of Alnustone in Rats after Intravenous Administration by Liquid Chromatography-Mass Spectrometry

Published:1 September 2019 DOI: 10.3390/molecules24173183
Yang Song,?Yu Zhou,?Xiao-ting Yan,?Jinguang Bi,?Xin Qiu,?Yu Bian,?Kefei Wang,?Y. Zhang,?Xue-song Feng

Abstract

Alnustone, a nonphenolic diarylheptanoid, first isolated from Alnus pendula (Betulaceae), has recently received a great deal of attention due to its various beneficial pharmacological effects. However, its pharmacokinetic profile in vivo remains unclear. The purpose of this study is to establish a fast and sensitive quantification method of alnustone using liquid chromatography tandem mass spectrometry (LC-MS/MS) and evaluate the pharmacokinetic and tissue distribution profiles of alnustone in rats. The sample was precipitated with acetonitrile with 0.5% formic acid and separated on BEH C18 Column. The mobile phase was composed of 0.1% formic acid in water and methanol at a flow rate of 0.3 mL/min. Alnustone and the internal standard (caffeine) were quantitatively monitored with precursor-to-product ion transitions of m/z 262.9→105.2 and m/z 195.2→138.0, respectively. The calibration curve for alnustone was linear from 1 to 2000 ng/mL. The intra- and inter-day assay precision (RSD) ranged from 1.1–9.0 % to 3.3–8.6%, respectively and the intra- and inter-day assay accuracy (RE) was between ?8.2–9.7% and ?10.3–9.9%, respectively. The validated method was successfully applied to the pharmacokinetic studies of alnustone in rats. After single-dose intravenous administration of alnustone (5 mg/kg), the mean peak plasma concentration (Cmax) value was 7066.36 ± 820.62 ng/mL, and the mean area under the concentration-time curve (AUC0–t) value was 6009.79 ± 567.30 ng/mL?h. Our results demonstrated that the residence time of alnustone in vivo was not long and it eliminated quickly from the rat plasma. Meanwhile, the drug is mainly distributed in tissues with large blood flow, and the lung and liver might be the target organs for alnustone efficacy. The study will provide information for further application of alnustone.

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Materials
Procduct Name CAS Molecular Formula Supplier Price
(4E,6E)-1,7-Diphenyl-4,6-heptadien-3-one 33457-62-4 C19H18O 162 suppliers Inquiry
(4E,6E)-1,7-Diphenyl-4,6-heptadien-3-one 33457-62-4 C19H18O 162 suppliers Inquiry
(4E,6E)-1,7-Diphenyl-4,6-heptadien-3-one 33457-62-4 C19H18O 162 suppliers Inquiry
(4E,6E)-1,7-Diphenyl-4,6-heptadien-3-one 33457-62-4 C19H18O 162 suppliers Inquiry
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