Department of Pharmacology, School of Basic Medical Sciences, Capital Medical Universit; Beijing Laboratory of Biomedical Detection and Instrument, Beijing 100069, China.
Department of Pharmacology, School of Basic Medical Sciences, Capital Medical Universit; Beijing Laboratory of Biomedical Detection and Instrument, Beijing 100069, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jan 1;944:128-35. doi: 10.1016/j.jchromb.2013.11.024. Epub 2013 Nov 22.
Lapachol is a natural naphthoquinone compound derived from Bignoniaceae (Tabebuia sp.) that possesses a range of significant biological activities. Nine phase I and four phase II metabolites of lapachol in rat bile were firstly elucidated and identified using a sensitive LC-ESI-MS(n) method. The molecular structures of the metabolites have been presented on the basis of the characteristics of their precursor and product ions, as well as their fragmentation mechanisms and chromatographic retention times. The results indicated that the phase I metabolites were predominantly biotransformed by the hydroxylation, semiquinone hydrogenation at the oxygen position or a side chain rearrangement. The phase II metabolites were identified as the glucuronidated conjugates which showed a characteristic neutral loss of 176Da. Based on the results of this research, we have proposed the metabolic pathways for lapachol in rats. This work has provided novel information for the in vivo lapachol metabolism which could be used to develop a novel drug candidate, as well as a better understanding of the safety and efficacy of the drug.
拉帕醌是一种天然萘醌化合物，来源于紫葳科（Tabebuia sp.），具有多种重要的生物活性。本文采用灵敏的 LC-ESI-MS(n) 方法，首次阐明并鉴定了大鼠胆汁中拉帕醌的 9 种 I 相代谢物和 4 种 II 相代谢物。根据前体离子和产物离子的特征、碎裂机制以及色谱保留时间，提出了代谢物的分子结构。结果表明，I 相代谢物主要通过羟基化、氧位或侧链重排的半醌氢化为特征进行生物转化。II 相代谢物被鉴定为葡萄糖醛酸化缀合物，其特征为 176Da 的中性丢失。基于这些研究结果，我们提出了拉帕醌在大鼠体内的代谢途径。这项工作为体内拉帕醌代谢提供了新的信息，可用于开发新的候选药物，并更好地了解药物的安全性和疗效。
