LC-ESI-MS-MS Determination of Rat Plasma Protein Binding of Major Flavonoids of Flos Lonicerae Japonicae by Centrifugal Ultrafiltration
LC-ESI-MS-MS Determination of Rat Plasma Protein Binding of Major Flavonoids of Flos Lonicerae Japonicae by Centrifugal Ultrafiltration
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LC-ESI-MS-MS 离心超滤法测定金银花主要黄酮类化合物与大鼠血浆蛋白的结合
DOI：
10.1365/s10337-010-1618-6
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发表时间：
2010-07-01
期刊：
影响因子：
1.7
通讯作者：
Li, Ping
中科院分区：
文献类型：
--
作者：
Luo, Yongdong;Wu, Shuisheng;Li, Ping
建立了离心超滤(CU)和快速液相色谱-电喷雾电离串联质谱仪(LC-ESI-MS-MS)分析金银花中4种黄酮类成分的药物-蛋白质结合分析方法。用CU实现了血浆中游离药物的快速分离，并用FAST LC-ESI-MS-MS同时测定了大鼠血浆中Flj的4种黄酮类成分。使用4.6m m×1.8mμm反相柱和MS-MS模式进行多反应监测，在不影响分辨率的情况下，色谱分析时间降至6.5min。灌胃给药后，4种黄酮类成分的蛋白结合率在66.8±97.4%~81.3±95.1%之间。在30、45和80分钟时，所有数值均接近70.0%。结果表明，这些黄酮类化合物在大鼠血浆中表现出较高的蛋白质结合率，并在较长时间内呈现稳定的结合。同时也揭示了这些黄酮类化合物在体内的消除可能比较温和，表现为一定程度的蓄积，并对药代动力学参数产生进一步的影响。
Centrifugal ultrafiltration (CU) and a fast liquid chromatography with electrospray ionization tandem mass spectrometric (LC-ESI-MS-MS) method have been developed for drug-protein binding analysis of four flavonoids of Flos Lonicerae Japonicae (FLJ). A rapid separation of free drug from the plasma was achieved by CU and the simultaneous analysis of four flavonoids of FLJ in rat plasma was by fast LC-ESI-MS-MS. The chromatographic analytical time decreased to 6.5 min without sacrificing resolution using a 4.6 mm × 50 mm, 1.8 μm particle size reverse phase column and MS–MS mode performed for multiple reaction monitoring (MRM). The protein binding rates of four flavonoids were in the range of 66.8 ± 7.4 to 81.3 ± 5.1% after oral administration of the flavonoid fraction of FLJ. All values were almost similar to 70.0% at 30, 45 and 80 min. Its result suggests that these flavonoids in rat plasma perform high protein binding rates and present a stable binding in a longer time. Meanwhile, it reveals that the elimination of these flavonoids may be relatively moderate in the body, the performance of a certain degree of accumulation may be speculated and make further impacts on the pharmacokinetic parameters.