Simultaneous determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re and 20(5) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a Panax notoginseng saponin preparation

Simultaneous determination of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re and 20(5) protopanaxatriol in beagle dog plasma by ultra high performance liquid mass spectrometry after oral administration of a Panax notoginseng saponin preparation
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DOI:
10.1016/j.jchromb.2014.10.025
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发表时间:
2015-01-01
影响因子:
3
通讯作者:
Du, Shouying
Du, Shouying
中科院分区:
医学3区
文献类型:
--
作者:
Wu, Huichao;Liu, Huimin;Du, Shouying

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20(S)原人参三醇是三七中三七皂苷R-1、三七皂苷Rg(1)、三七皂苷Re的主要代谢产物,具有显著的药理活性。建立了一种超高效液相色谱质谱法,用于测定犬口服三七总皂苷制剂后血浆中三七皂苷R1、Rg(1)、Re和20(S)原人参三醇(PPT)的含量。加入内标物(地高辛)后,用丙酮和甲醇对血浆样品进行液-液萃取,并在100 x 2.1 mm ACQUITY 1.7 μ m C-18色谱柱上分离(沃茨,USA),乙腈和水作为移动的相,在选择反应监测模式下,随着电喷雾离子化从阳性变为阴性,分析物被检测而无干扰。方法的检出限为0.01 ~ 0.04 mg/L,四种成分的峰面积在四个数量级内呈线性关系,相关系数大于0.9957。日内和日间精密度(RSD,%)分别在10.25%和13.51%以内,准确度(相对误差,RE,%)小于7.81%。该方法已成功应用于比格犬口服三七皂苷制剂后4种皂苷的药代动力学比较研究。采用DAS 3.20软件计算药动学参数。Tmax和C-max值表明皂苷(R-1、Rg(1)和Re)与其皂苷配基(PPT)之间存在剂量-剂量关系。(C)2014爱思唯尔有限公司版权所有。
20(S) protopanaxatriol is the main metabolite of notoginsenoside R-1, ginsenoside Rg(1), ginsenoside Re in Panax no toginseng and has significant activities. A ultra high performance liquid mass spectrometry method has been developed and validated for the simultaneous determination of notoginsenoside R-1 (R1), ginsenoside Rg(1) (Rg(1)), ginsenoside Re (Re) and 20(S) protopanaxatriol (PPT) in beagle dog plasma after oral administration of a Panax notoginseng saponin preparation. After the addition of the internal standard (digoxin), plasma samples were subjected to liquid-liquid extraction with acetone and methanol and separated on a 100 x 2.1 mm ACQUITY 1.7 mu m C-18 column (Waters, USA), with acetonitrile and water as the mobile phase, within a runtime of 7.0 min. The analytes were detected without interference in Selected Reaction Monitoring mode with a change in the electrospray ionization from positive to negative. The detection limits were 0.01 to 0.04 mg/L and the calibration curves of the peak areas for the four ingredients were linear over four orders of magnitude with a correlation coefficient greater than 0.9957. The intra-day and inter-day precision values (relative standard deviation, RSD, %) were within 10.25% and 13.51%, respectively, and the accuracy (relative error, RE, %) was less than 7.81%. The validated method was successfully applied to a comparative pharmacokinetic study of four saponins in beagle dogs after oral administration of a Panax Notoginseng Saponins preparation. The pharmacokinetic parameters were calculated with DAS 3.20. The T-max and C-max values indicate a dose-dose relationship between the saponins (R-1, Rg(1), and Re) and their sapogenin (PPT). (C) 2014 Elsevier B.V. All rights reserved.