Yan-Yan Z, Li-Li G, Guo-Ming S, Rong R, Jing-Zhen T
Shandong University of Traditional Chinese Medicine, Jinan, China.
Drug Res (Stuttg). 2016 Oct;66(10):520-526. doi: 10.1055/s-0042-111904. Epub 2016 Aug 4.
A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the quantification of ginkgolides in rat plasma, and the main pharmacokinetic parameters of ginkgolides after oral administration of Ginkgo biloba extract (GBE) was acquired. Plasma samples were pretreated with ethyl acetate extraction. Sulfamethoxazole was used as the internal standard (IS). Chromatographic separation was achieved on an Eclipse XDB-C18 column (2.1 mm×150 mm, 5 μm) with a mobile phase consisting of methanol/0.1% formic acid water (gradient elution: 0~25 min (77:23)→(60:40), V/V) at a flow rate of 0.3 mL·min. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization (ESI) source for 25 min. The detection was operated by multiple reaction monitoring(MRM) under negative ionization mode of the transitions of m/z 325→163 for BB, 469→423 for GJ, 439→125 for GC, 453→351 for GA, 423→367 for GB and of m/z 252→156 for sulfamethoxazole (IS) respectively. The pharmacokinetic properties of BB, GJ, GA, GB and GC were in line with the open 2-compartment model after oral administration of GBE in rats; The pharmacokinetic parameters of various lactones were calculated, and drugs-time curve and the curve fitting diagram of 5 ginkgolides were drew; The absorption and distribution rate of BB, GJ, GA, GB and GC were fast in rats in vivo, and half-life of absorption was less than 3 h. The developed LC-ESI (-)/MS/MS (QQQ) method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of ginkgolides in rats after administration of GBE, which can provide basis for further clinical efficacy studies.
已开发并验证了一种简单、快速且特异的高效液相色谱-串联质谱法，用于定量大鼠血浆中的银杏内酯，并获得了口服银杏叶提取物（GBE）后银杏内酯的主要药代动力学参数。血浆样品用乙酸乙酯萃取进行预处理。磺胺甲恶唑用作内标（IS）。在Eclipse XDB-C18柱（2.1 mm×150 mm，5μm）上进行色谱分离，流动相为甲醇/0.1%甲酸水（梯度洗脱：0~25 min（77:23）→（60:40），V/V），流速为0.3 mL·min。在三重四极杆串联质谱仪上使用电喷雾电离（ESI）源进行25 min检测。检测在负离子模式下通过多反应监测（MRM）进行，BB的m/z 325→163、GJ的m/z 469→423、GC的m/z 439→125、GA的m/z 453→351、GB的m/z 423→367以及磺胺甲恶唑（IS）的m/z 252→156分别作为跃迁。大鼠口服GBE后，BB、GJ、GA、GB和GC的药代动力学性质符合开放二室模型；计算了各种内酯的药代动力学参数，并绘制了5种银杏内酯的药物-时间曲线和曲线拟合图；BB、GJ、GA、GB和GC在大鼠体内的吸收和分布速率较快，吸收半衰期小于3 h。所建立的LC-ESI（-）/MS/MS（QQQ）方法成功应用于评估大鼠口服GBE后银杏内酯的药代动力学参数和口服生物利用度，可为进一步的临床疗效研究提供依据。
