Zhang Sainan, Ju Zhengcai, Guan Huida, Yu Lu, Wang Zhengtao, Zhao Yuqing
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China.
The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Biomed Chromatogr. 2019 Nov;33(11):e4670. doi: 10.1002/bmc.4670. Epub 2019 Aug 28.
Notoginsenoside R (NGR ), a diagnostic protopanaxatriol-type (ppt-type) saponin in Panax notoginseng, possesses potent biological activities including antithrombotic, anti-inflammatory, neuron protection and improvement of microcirculation, yet its pharmacokinetics and metabolic characterization as an individual compound remain unclear. The aim of this study was to investigate the exposure profile of NGR in rats after oral and intravenous administration and to explore the metabolic characterization of NGR . A simple and sensitive ultra-fast liquid chromatographic-tandem mass spectrometric method was developed and validated for the quantitative determination of NGR and its major metabolites, and for characterization of its metabolic profile in rat plasma. The blood samples were precipitated with methanol, quantified in a negative multiple reaction monitoring mode and analyzed within 6.0 min. Validation parameters (linearity, precision and accuracy, recovery and matrix effect, stability) were within acceptable ranges. After oral administration, NGR exhibited dose-independent exposure behaviors with t over 8.0 h and oral bioavailability of 0.25-0.29%. A total of seven metabolites were characterized, including two pairs of epimers, 20(R)-notoginsenoside R /20(S)-notoginsenoside R and 20(R)-ginsenoside Rh /20(S)-ginsenoside Rh , with the 20(R) form of saponins identified for the first time in rat plasma. Five deglycometabolites were quantitatively determined, among which 20(S)-notoginsenoside R , ginsenoside Rg , ginsenoside F and protopanaxatriol displayed relatively high exploration, which may partly explain the pharmacodynamic diversity of ginsenosides after oral dose.
三七皂苷R1（NGR）是三七中一种具有诊断价值的原人参三醇型（ppt型）皂苷，具有多种强大的生物活性，包括抗血栓形成、抗炎、神经保护和改善微循环等作用，但其作为单一化合物的药代动力学和代谢特征仍不清楚。本研究旨在研究大鼠口服和静脉给药后NGR的暴露情况，并探索NGR的代谢特征。建立了一种简单灵敏的超快速液相色谱-串联质谱法，用于定量测定NGR及其主要代谢产物，并表征其在大鼠血浆中的代谢谱。血样用甲醇沉淀，在负模式多反应监测下进行定量，并在6.0分钟内完成分析。验证参数（线性、精密度和准确度、回收率和基质效应、稳定性）均在可接受范围内。口服给药后，NGR呈现剂量非依赖性暴露行为，t超过8.0小时，口服生物利用度为0.25-0.29%。共鉴定出7种代谢产物，包括两对差向异构体，20（R）-三七皂苷R1/20（S）-三七皂苷R1和20（R）-人参皂苷Rh1/20（S）-人参皂苷Rh1，其中皂苷的20（R）形式首次在大鼠血浆中被鉴定。定量测定了5种去糖代谢产物，其中20（S）-三七皂苷R1、人参皂苷Rg1、人参皂苷F1和原人参三醇的探索率相对较高，这可能部分解释了人参皂苷口服给药后的药效学多样性。
