Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, The MOE Key Laboratory for Standardization of Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Shanghai, P. R. China.
Shanghai R&D Centre for Standardization of Chinese Medicines, Shanghai, P. R. China.
J Sep Sci. 2019 Apr;42(8):1550-1563. doi: 10.1002/jssc.201801295. Epub 2019 Mar 10.
Notoginsenoside Fc, a protopanaxadiol-type saponin, shows multi-pharmacological activities. Chemical stability evaluation plays a crucial role in drug development. In this study, the forced degradation behavior of Notoginsenoside Fc was investigated under hydrolytic and oxidative conditions. A specific ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed for the separation, identification, and characterization of the degradation products of Notoginsenoside Fc. Fifty potential degradation products were formed via deglycosylation, dehydration, hydration, isomerization, side-chain cleaving, oxidation, and superoxidation. Notoginsenoside Fc was subjected to different pH solutions, temperatures, and time periods to assess its stability. A sensitive ultra high performance liquid chromatography-tandem mass spectrometry was developed for the quantification of Notoginsenoside Fc, notoginsenoside ST-4, notoginsenoside Ft1, and relative quantification of notoginsenoside Ft2, 20(R)-notoginsenoside Ft2, notoginsenoside SFt3, and notoginsenoside SFt4. The assay was linear over the concentration range (R > 0.997) with the lowest limit of quantification of 0.02 μg/mL for Notoginsenoside Fc, Notoginsenoside ST-4, and Notoginsenoside Ft1. The intra-day precision, inter-day precision, and accuracy of the three analytes were within accepted levels. The degradation kinetics of Notoginsenoside Fc in pH 1 and 3 solutions fits to first- and second-order kinetics, respectively. The degradation of Notoginsenoside Fc is pH-, temperature-, and time-dependent.
三七总皂苷 Fc 是一种原人参二醇型皂苷，具有多种药理活性。化学稳定性评估在药物开发中起着至关重要的作用。在这项研究中，研究了三七总皂苷 Fc 在水解和氧化条件下的强制降解行为。建立了一种特定的超高效液相色谱-四极杆飞行时间质谱法，用于分离、鉴定和表征三七总皂苷 Fc 的降解产物。通过去糖基化、脱水、水合、异构化、侧链断裂、氧化和超氧化作用，形成了 50 种潜在的降解产物。将三七总皂苷 Fc 置于不同的 pH 溶液、温度和时间段下，以评估其稳定性。建立了一种超高效液相色谱-串联质谱法，用于定量分析三七总皂苷 Fc、三七皂苷 ST-4、三七皂苷 Ft1，以及相对定量分析三七皂苷 Ft2、20(R)-三七皂苷 Ft2、三七皂苷 SFt3 和三七皂苷 SFt4。该测定法在浓度范围内（R>0.997）呈线性关系，三七总皂苷 Fc、三七皂苷 ST-4 和三七皂苷 Ft1 的最低定量限为 0.02μg/mL。三种分析物的日内精密度、日间精密度和准确度均在可接受范围内。三七总皂苷 Fc 在 pH 1 和 3 溶液中的降解动力学分别符合一级和二级动力学。三七总皂苷 Fc 的降解是 pH、温度和时间依赖性的。
