大鼠口服雄黄和牛黄解毒片后血浆中砷形态的研究-药学学报.PDF

大鼠口服雄黄和牛黄解毒片后血浆中砷形态的研究 1 2 2* 2** 张云静 ，强淑萍 ，宋敏 ，杭太俊 (1. 安徽中医药大学药学院, 安徽 合肥 230012; 2. 中国药科大学药物分析教研室, 江苏 南京210009) 摘要: 研究大鼠灌胃雄黄和牛黄解毒片后血浆中各形态的砷化合物的经时过程，比 较雄黄单味药与牛黄解毒片全方给药后各形态的砷的药动学差异。采用高效液相色 谱 氢化物发生 原子荧光联用技术 (HPLC HG AFS) 检测大鼠血浆中四种形态的 砷化合物。大鼠灌胃雄黄和牛黄解毒片后血浆中的主要砷形态为二甲基砷酸 （DMA ），其它形态的砷化合物：亚砷酸盐[As(III)]、一甲基砷酸（MMA ）和砷酸 盐[As(V)]在各时间点均未检测到。大鼠灌胃牛黄解毒片后，与单味雄黄相比，经剂 量校正后DMA 的Cmax 和AUC 显著降低，Tmax 显著延长，清除率和表观分布容积显 著增加，表明牛黄解毒片复方配伍对砷的药动学行为有影响。 关键词: 砷形态；血浆；雄黄；牛黄解毒片 中图分类号：R917 文献标识码：A 文章编号： Arsenic speciation in rat plasma after oral administration of realgar and Niu Huang Jie Du Pian Abstract: The arsenic species in rat plasma after oral administration of realgar and Niu Huang Jie Du Pian (NHJDP) were studied and the possible compatible effects of realgar was evaluated by comparing the pharmacokinetics of arsenic species after administration of realgar and NHJDP. The separation of the arsenicals was performed by a high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) technique. Dimethylarsinic acid (DMA) was found to be the main species in rats’ plasma after dosing. No traces of arsenite [As(III)], monomethylarsonic acid (MMA) or arsenate [As(V)] were detected at any sampling time points. Compared with realgar administration alone, dose normalized peak concentration (Cmax) and AUC0-t of DMA was significantly decreased by NHJDP administration, while the tmax was 收稿日期：2016-01-08 ；修回日期：2016-03-08. 基金项目: 国家自然科学基金资助项目 (No.. * 通讯作者：Tel: 025 E-mail: cqsongmin@ E-mail: hangtj@ 1 significantly delayed with the clearance and apparent volume of distribution significantly increased, indicating tha