LC-MS/MS测定比格犬血浆中的醉茄素A及其生物利用度研究  

Determination of Withaferin A in Beagle Dog Plasma by LC-MS/MS and Its Application to a Bioavailability Study

作　　者：戴天明 王敏 DAI Tian-ming;WANG Min(Guangzhou Red Cross Hospital,Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan Universityl/Guangzhou Trauma Surgery Research Institute/Guangzhou Guangdong 510220,China;Orthopaedics,Guangzhou Red Cross Hospital/Guangzhou Red Cross Hospital Affiliated to Medical College of Jinan University,Guangzhou Guangdong 510220,China)

机构地区：[1]广州市红十字会医院/暨南大学医学院附属广州红十字会医院/广州市创伤外科研究所,广东广州510220 [2]广州市红十字会医院/暨南大学医学院附属广州红十字会医院骨科,广东广州510220

出　　处：《药品评价》2020年第1期14-14,69,共2页Drug Evaluation

基　　金：广东省省级科技计划项目(2013A022100019)。

摘　　要：醉茄素A(WA)是植物南非醉茄中的主要生物活性成分,具有抗肿瘤和抗肥胖等药理作用。虽然南非醉茄提取物的口服保健产品已上市多年,但WA的口服生物利用度仍不清楚。本研究首先建立灵敏、高效的WA血浆样品LC-MS/MS分析方法,然后在比格犬分别进行静脉注射和口服灌胃WA的两周期药代动力学实验。实验结果表明,WA在比格犬的口服生物利用度较高(42.2%±6.4%),吸收快,而且具有较长的半衰期[(18±4.6)h]和较大的表观分布容积[(67.5±8.9) L/kg],有利于药物长时间在体内发挥药效。因此,WA总体上具有良好的药代动力学性质,可作为口服候选药物,进一步评估成药性和进行临床前开发,为临床应用提供依据。Withaferin A(WA)is the main bioactive component in the plant Withania somnifera, which has been reported to have antitumor and antiobesity effects. Although the extract product of Withania somnifera has been on the market for many years, the bioavailability of WA remains unclear. In this study, a sensitive and efficient LC-MS/MS method was established for the analysis of WA in plasma, and two-cycle pharmacokinetics experiments of intravenous or oral administration of WA were carried out in beagle dogs. The results showed that the bioavailability of WA in beagle dogs was high(42.2%±6.4%), and the absorption was fast. WA had a long half-life[(18±4.6)h]and a large Vd[(67.5±8.9)L/kg], which was conducive to the drug’s long-term efficacy in vivo. Therefore, WA has good pharmacokinetic properties, which can be used as a candidate drug for oral administration. Further evaluation and preclinical R&D will provide basis for clinical application.

关 键 词：醉茄素A 药代动力学 生物利用度 LC-MS/MS 

分 类 号：R965[医药卫生—药理学]