灯盏花素在正常和模型大鼠中的药代动力学及代谢物研究

Pharmacokinetics and metabolites of scutellarin in normal and model rats

目的研究灯盏花素在正常和角叉菜胶致血栓形成大鼠中的药代动力学,并对其血浆样品中主要代谢物进行初步鉴定.方法RP-HPLC法测定静注36 mg·kg-1灯盏花素后正常和模型大鼠不同时间血浆样品中灯盏乙素浓度,3P97软件拟合房室模型,计算药动学参数;HPLC-PDA(光电二极管阵列)、LC-MS/MS技术分析鉴定血浆样品中的主要色谱峰.结果血浆中灯盏乙素在0.625～80.0μg·mL-1(r=0.999 5)线性关系良好,最低定量浓度:0.312μg·mL-1;正常和角叉菜胶致血栓形成状态下,灯盏乙素药时曲线均呈现二室开放模型.血浆样品中4个主要色谱峰的可能结构分别为4',5-二羟基黄酮-7-氧-β-D-葡糖醛酸甲酯苷(M1)、灯盏乙素(M2)、7-甲氧基-4',5-二羟基-黄酮(M3)和7-甲氧基-4',5,6-三羟基-黄酮(M4).结论正常和模型大鼠体内灯盏乙素的药动学参数有显著性差异;灯盏乙素在大鼠血浆样品中的代谢主要是脱羟基和甲基化途径.

Aim To investigate the pharmaeokineties and metabolites of scutellarin in normal rats and rats with thronlbosis model induced by earrageenan. Methods Scutellarin was assayed by reverse phase high performance liquid ebromalography in various plasma samples after a single dose of 36 mg· kg^-1 iv to each rat, the pharmaeokinetie parameters were estimated by 3P97 program. The metabolites of seutellarin in blood 2ere ehromatographed and identified by HPLC-PDA, LC/MS/MS. Results The calibration curve was linear over the range fiom 0. 625 to 80. 0 μg· mL^-1 （r =0. 999 5 ） , the limit quantitation was 0. 312 μg· mL^-1. The plasma seutellarin eoneemration-time curve was fitted to the open two-compartment model. In the plasma samples, the main metabolites were deduced as 4＇,5-dihydroxyflavonon-7-O-β-D-glucuronopyranosyl ester （ M 1 ）, scutellarin （ M2 ）, 7-methoxy-4＇ ,5-dihydroxy-flavonon （ M3 ） and 7-methoxy-4＇ ,5,6-dihydroxy- flavonon （M4）. Conclusion The phammeokinetic parameters of scutellarin were significantly different in normal and model rats. The metabolic pathways of seutellarin was proposed to be dehydroxylation and methylation.