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巴豆苷的药代动力学及组织分布

Pharmacokinetics and tissue distribution of crotonoside.

作者信息

Yan Peiao, Zhang Lan, Peng Cheng, Zhang Ruoqi

机构信息

a Pharmacy College, Chengdu University of Traditional Chinese Medicine , Chengdu , China.

b The Ministry of Education Key Laboratory of Standardization of Chinese Herbal Medicine , Chengdu , China , and.

出版信息

Xenobiotica. 2018 Jan;48(1):28-36. doi: 10.1080/00498254.2016.1276311. Epub 2017 Jan 19.

DOI:10.1080/00498254.2016.1276311
PMID:28100102
Abstract

1. Crotonoside is a bioactive ingredient from Croton Herba with a strong antitumour activity. This study aimed to develop a highly sensitive and selective high-performance liquid chromatography (HPLC) method to quantify crotonoside in biological samples for pharmacokinetics and distribution studies. 2. Protein precipitation by perchloric acid was used to separate crotonoside from the biological samples, and the recovery rates for crotonoside and the internal standard (luteoloside) were  >80%. All calibration curves examining the crotonoside levels in plasma and tissues were linear (all correlation coefficients > 0.99). 3. The response to crotonoside appeared to be dose disproportional to the maximum plasma concentration and the area under the time-concentration curve in plasma over the range of 12.5-50.0 mg/kg, and crotonoside was highly distributed in tissues after intravenous administration. The highest crotonoside level was detected in the liver (28.79 ± 14.96 μg/g), whereas crotonoside was undetected in the brain.

摘要
  1. 巴豆苷是一种来自巴豆草的具有强大抗肿瘤活性的生物活性成分。本研究旨在开发一种高灵敏度和选择性的高效液相色谱(HPLC)方法,用于定量生物样品中的巴豆苷,以进行药代动力学和分布研究。2. 采用高氯酸沉淀蛋白法从生物样品中分离巴豆苷,巴豆苷和内标(木犀草苷)的回收率均>80%。所有检测血浆和组织中巴豆苷水平的校准曲线均呈线性(所有相关系数>0.99)。3. 在12.5 - 50.0 mg/kg范围内,巴豆苷的反应与最大血浆浓度和血浆中时间-浓度曲线下面积似乎呈剂量不成比例关系,静脉给药后巴豆苷在组织中分布广泛。在肝脏中检测到最高的巴豆苷水平(28.79±14.96μg/g),而在脑中未检测到巴豆苷。

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