摘要
目的建立大鼠血浆中木犀草素和芹菜素总浓度的HPLC测定方法，并研究大鼠口服菊花提取物（CME）后其效应成分——木犀草素、芹菜素的药动学参数。方法大鼠血浆在2mol·L^-1盐酸酸性条件下于80℃水浴水解1．5h，水解液经乙酸乙酯萃取，萃取液减压抽干后溶解，经HPLC分析。采用Diamonsil ODS C18色谱柱，以甲醇-0．2％磷酸（55：45）为流动相，流速1．0mL·min^-1，检测波长350nm，柱温30℃。应用建立的方法测定大鼠口服200mg·kg^-1菊花提取物后血浆中木犀草素及芹菜素质量浓度，并以3P87软件计算其药动学参数。结果本法木犀草素和芹菜素的定量下限（LOQ）分别为0．0455和0．145mg·L^-1；两者分别在0．0455～8．09和0．145～25．7mg·L^-1内呈良好线性关系，r分别为0．9957及0．9974；两者低、中、高质量浓度的绝对回收率及方法回收率均在89％～107％内。日间及日内精密度RSD均小于〈11％。大鼠口服CME后木犀草素与芹菜素的K分别为1．72和0．237h；t1／2（Ka）分别为0．440和3．21h；t1/2a分别为0．774和4．82h；t1／2β分别为6．64和8．65h；tmax分别为0．730和2．91h；pmax分别为2．43和9．00mg·L^-1；AUC分别为21．40和143mg·h·L^-1。结论本研究建立的方法准确可靠、，操作简便重复性好，适用于测定血浆中木犀草素及芹菜素浓度.
OBJECTIVE To establish a RP-HPLC method for the determination of total luteolin and apigenin in rat plasma after acid hydrolysis and to apply the method for pharmacokinetics study after a single dose of Chrysanthemum morifolium extract （CME） in rats . METHODS The samples were hydrolyzed with 2. 0 mol · L^-1 hydrochloric acid（c =2 mol · L^-1 ） at 80 ℃ water bath for 1.5 h, the mixed solution were extracted with ethyl acetate. The organic layer separated was blown to dry and dissolved reconstituted in the mobile phase. The HPLC separation was performed on a C18 column and the UV detector wavelength was set at 350 nm. The plasma samples were analyzed after an oral administration of CME to rat （200 mol · L^-1） by the developed method, the pharmacokinetic pa- rameters were valuated by 3P87 software. RESULTS Good linearities of luteolin and apigenin were obtained over the range of 0. 045 5 - 8. 09 mol · L^-1 , and 0. 145 · 25. 7 mol · L^-1 in plasma, respectively. The recoveries of luteolin and apigenin were from 89% to 107%. The precisions of intra-day and inter-day were all less than 11%. The main pharmacokinetics parameters were as follows：ka of luteolin and apigenin was 1.72 and 0. 237 h^-1 ;t1/2（ka） 0. 440 and 3.21 h;t1/2a,0. 774 and 4. 82 h;t1/2（β） 9. 88 and 8. 65 h, respectively ;tmax 0.730 and 2.91 h;pmax 2.43 and 9.00 mg · L^-1;AUC 21.04 and 143 mg · h · L^-1. CONCLUSION The method developed is sensitive, accurate and reproducible, and can be applied to the determination of luteolin and apigenin in plasma.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2007年第5期374-378,共5页
Chinese Pharmaceutical Journal
基金
浙江省自然科学基金(Y204379)
浙江省科技厅重点项目(G20020578)
