Xiong Yang, Chen Jianming, Guo Dan
Department of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang, China.
Department of Pharmaceutical Science, School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2014 Jul 1;962:132-140. doi: 10.1016/j.jchromb.2014.03.039. Epub 2014 May 5.
Nobiliside A (Nob) is a new triterpenoid saponin separated from Holothuria noblilis. In this article, a liquid chromatography-electrospray ionization-tandem mass spectrometry method was established to quantify Nob, a hemolytic saponin, in rat blood and tissue homogenates. Standard curves were linear (r=0.9988-0.9995) over the range 50-5000ng/mL in blood and 100-10000ng/g in tissues. The lower limit of quantification (LLOQ) was 50ng/mL for Nob. The novel method was rapid, accurate, highly sensitive and highly selective. Using this method, the pharmacokinetics and biodistribution of Nob liposome and Nob solution in Sprague-Dawley rats after a single intravenous dose of 1mg/kg were then investigated. Nob was cleared slowly from circulation. There was no significant difference of the pharmacokinetic parameters in blood between Nob solution and Nob liposome. The highest AUC of Nob was observed in liver for the two groups, followed by spleen, lungs, kidney and heart. Compared with Nob solution, Nob liposome showed much higher AUC in liver and spleen and much lower AUC in kidney, heart and lung, which might be one important reason for the decreased toxicity of Nob.
诺比皂苷A（Nob）是从华贵栉孔扇贝中分离得到的一种新型三萜皂苷。在本文中，建立了一种液相色谱 - 电喷雾电离 - 串联质谱法来定量测定大鼠血液和组织匀浆中溶血皂苷Nob的含量。标准曲线在血液中50 - 5000ng/mL以及组织中100 - 10000ng/g范围内呈线性（r = 0.9988 - 0.9995）。Nob的定量下限（LLOQ）为50ng/mL。该新方法快速、准确、高灵敏且高选择性。使用此方法，随后研究了在单次静脉注射1mg/kg剂量后，Nob脂质体和Nob溶液在斯普拉格 - 道利大鼠体内的药代动力学和生物分布情况。Nob从循环系统中清除缓慢。Nob溶液和Nob脂质体在血液中的药代动力学参数无显著差异。两组中Nob在肝脏中的AUC最高，其次是脾脏、肺、肾脏和心脏。与Nob溶液相比，Nob脂质体在肝脏和脾脏中的AUC更高，而在肾脏、心脏和肺中的AUC更低，这可能是Nob毒性降低的一个重要原因。
