摘要
建立大鼠血浆中槲皮素、山柰素、异鼠李素的HPLC-MS/MS分析方法,用于沙棘膏中3种黄酮类成分在正常大鼠体内的药代动力学研究。该实验选用正常SD大鼠,单剂量灌胃沙棘膏（槲皮素26.35 mg·kg-1、山柰素4.040 mg·kg-1、异鼠李素31.37 mg·kg-1）后不同时间点采血,采用高效液相色谱-质谱连用（HPLC-MS/MS）系统进行槲皮素、山柰素、异鼠李素血药浓度测定,以kinetica 5.0.11软件,对数据进行二房室动力学拟合,计算主要药动学参数。经方法学考证,槲皮素、山柰素、异鼠李素的线性范围分别为7.500~600.0μg·L-1（R2=0.998 5）,1.000~80.00μg·L-1（R2=0.998 5）,10.00~800.0μg·L-1（R2=0.998 0）,日内、日间精密度RSD≤14%,血浆样品冻融1次,-20℃放置15 d,室温放置6 h以及处理后的分析物-20℃放置24 h的稳定性均良好,符合生物样品分析要求。大鼠灌胃沙棘膏后的药代参数如下,槲皮素t1/2β（113.3±19.37）h,AUC0-t（12 542.14±3 504.05）μg·h·L-1,MRT0-∞（119.6±13.29）h,Cmax（164.6±27.33）μg·L-1,Tmax（5.199±0.840 3）h;山柰素t1/2β（79.85±17.15）h,AUC0-t（934.51±94.59）μg·h·L-1,MRT0-∞（81.50±13.75）h,Cmax（80.15±14.24）μg·L-1,Tmax（3.827±0.902 7）h;异鼠李素t1/2β（118.3±20.73）h,AUC0-t（26 067.77±4 124.60）μg·h·L-1,MRT0-∞（129.0±16.30）h,Cmax（269.6±29.32）μg·L-1,Tmax（6.513±1.450）h。该文所建立的灵敏、准确的HPLC-MS/MS检测方法适用于大鼠血浆中槲皮素、山柰素、异鼠李素成分的药代动力学研究。
To establish an HPLC-MS/MS method for the analysis of quercetin, kaempferid and isorhamnetin in rats plasma and study its pharmamacokinetics after an intragastrical administration of Hippophae rhamnoides extracts. Five healthy male Sprague-Dawley （SD） rats were given single doses of H. rhamnoides extracts （ quercetin 26. 35 mg ·kg- 1, kaempferid 4. 040 mg·kg- 1, isorhamnetin 31.37 mg · kg-1）, and then their orbital sinus blood samples were collected at different time points. The drug plasma concentration of the three flavonoids was determined by HPLC-MS/MS method. After that, the main pharmacokinetics parameters were calculated by using Kinetica 5.0. 11 software. The methodological test showed that the linear concentration ranges of quercetin, kaempferid and isorhamnetin were 7. 500-600. 0 μg · L-1 （R2 =0.998 5）, 1.000-80.00 μg · L - （R2 =0.998 5） and 10.00-800.0 μg ·L-1 （R2 =0. 998 0） , respectively. The inner and inter-days precisions were both less than 14. 0%. The plasma samples showed a good stability and consistency with the requirement of biological sample analysis after the samples were fi＇ozen once and placed at - 20 ℃ for 15 d and room temperature for 6 h and the treated analytes were placed at -20 ℃ for 24 h. For quercetin, the pharmacokinetic parameter t1/2β, AUCo, MRT0-∞, Cmax and Tmax were （ 113.3± 19.37 ） min, （ 12 542. 14 ± 3 504. 05 ） p,g · h ·L -1, （ 119. 6 ± 13.29） h,（164. 6 ±27.33） μg · L -1 and （5. 199 ±0. 840 3） h, respectively. For kaempferid, the pharmacokinetic parameters t1/2β, AUCo,, MRT0-∞, C max Tmax were （79. 85±17.15） min, （934. 51 ±94. 59） μg· h· L-1, （81.50±13.75） h, （80. 15±14.24） μg. L-1 and （3. 827 ±0. 902 7） h, respectively. For isorhamnetin, the pharmaeokinetie parameters t1/2β, AUC0-∞, MRT0-∞ , Cmax and T were （118.3 ±20. 73） rain, （26 067.77 ±4 124. 60） μg ·h · L-1 , （129. 0 ±16. 30） h, （269. 6±29. 32） μg · L-1 and （6. 513 ±1. 450） h, respect
出处
《中国中药杂志》
CAS
CSCD
北大核心
2015年第19期3859-3865,共7页
China Journal of Chinese Materia Medica
基金
四川省科技计划项目(2013SZ0114
2014SZ0071)
