文献类型：期刊文献

英文题名：A validated UPLC-MS/MS method for quantitative determination of a potent neuroprotective agent Sarsasapogenin-AA13 in rat plasma: Application to pharmacokinetic studies

作者：Pei, Lixia[1];Ye, Yiyi[1];Zhao, Wenshu[1];Ye, Qun[1];Ge, Songlan[1];Jiang, Zi-wei[1];Liang, Xiao-qiang[1];Gan, Hai-xian[2];Ma, Lei[2]

机构：[1]Shanghai Univ Tradit Chinese Med, Longhua Hosp, Shanghai 200032, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai 200237, Peoples R China

年份：2020

卷号：34

期号：3

外文期刊名：BIOMEDICAL CHROMATOGRAPHY

收录：;EI(收录号：20232414236287);WOS:【SCI-EXPANDED(收录号:WOS:000517115900022)】；

语种：英文

外文关键词：pharmacokinetics; neuroprotective effect; sarsasapogenin-AA13; UPLC-MS; MS

摘要：Sarsasapogenin-AA13(AA13), a sarsasapogenin derivative, exhibited good neuroprotective and anti-inflammatory activities in vitro and therapeutic effects on learning and memory dysfunction in amyloid-beta-injected mice. A sensitive UPLC-MS/MS method was developed and validated to quantitatively determine AA13 in rat plasma and was further applied to evaluate the pharmacokinetic behaviour of AA13 in rats that were administered AA13 intravenously and orally. This method was validated to exhibit excellent linearity in the concentration range of 1-1000 ng/mL. The lower limit of quantification was 1 ng/mL for AA13 in rat plasma. Intra-day accuracy for AA13 was in the range of 90-114%, and inter-day accuracy was in the range of 97-103 %. The relative standard deviation of intra-day and inter-day assay was less than 15%. After a single oral administration of AA13 at the dose of 25 mg/kg, C-max of AA13 was 1266.4 +/- 316.1 ng/mL. AUC(0-48 h) was 6928.5 +/- 1990.1 h.ng/mL, and t(1/2) was 10.2 +/- 0.8 h. Under intravenous administration of AA13 at a dosage of 250 mu g/kg, AUC(0-48 h) was 785.7 +/- 103.3 h.ng/mL, and t(1/2) was 20.8 +/- 7.2 h. Based on the results, oral bioavailability (F %) of AA13 in rats at 25 mg/kg was 8.82 %.