Determination and pharmacokinetic study of the novel anti-tumor candidate drug DG-7 in rat plasma by liquid chromatography-tandem mass spectrometry

作者:Li Juan; Liu Dan Dan; Ke Yu; Guo Fei; Ding Xiao Ming; Wang Shuai Liang; Chen Yu; Liu Hong Min*; Su Ying Qian; Nan Yan Yang
来源:Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2014, 960: 14-18.
DOI:10.1016/j.jchromb.2014.04.010

摘要

DG-7 (11,14-dihydroxy-7,20-epoxy-20-O-derivative of ent-kaurene diterpenoid) is a novel anti-tumor candidate drug. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of DG-7 in rat plasma. An aliquot of 50 mu L plasma sample was prepared by liquid-liquid extraction with ethyl acetate. Chromatographic separation was accomplished on a Waters XTerra C-18 column (2.1 mm x 150 mm, 5 mu m) with an isocratic elution system consisting of methanol and water. Detection was performed by multiple reaction monitoring (MRM) mode using electrospray ionization in the positive ion mode. The optimized fragmentation transitions for MRM were m/z 590.1 -> m/z 260.0 for DG-7 and m/z 180.3 -> m/z 110.1 for phenacetin (internal standard). The method was linear over the concentration range of 5-2500 ng/mL. The intra- and inter-day precisions were less than 7.9% and the accuracy was within +/- 9.0%. The mean recovery of DG-7 ranged from 76.8% to 79.2%. The validated method has been successfully applied to a pharmacokinetic study in rats after intravenous administration of DG-7.