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耳聋左慈丸在大鼠体内的药代动力学

顾云双, 王瑞, 苏娜, 彭英, 阿基业, 王广基, 郑亦文, 孙建国

顾云双, 王瑞, 苏娜, 彭英, 阿基业, 王广基, 郑亦文, 孙建国. 耳聋左慈丸在大鼠体内的药代动力学[J]. 中国药科大学学报, 2022, 53(4): 481-489. DOI: 10.11665/j.issn.1000-5048.20220411
引用本文: 顾云双, 王瑞, 苏娜, 彭英, 阿基业, 王广基, 郑亦文, 孙建国. 耳聋左慈丸在大鼠体内的药代动力学[J]. 中国药科大学学报, 2022, 53(4): 481-489. DOI: 10.11665/j.issn.1000-5048.20220411
GU Yunshuang, WANG Rui, SU Na, PENG Ying, A Jiye, WANG Guangji, ZHENG Yiwen, SUN Jianguo. Pharmacokinetic study of Erlong Zuoci Pill in rats[J]. Journal of China Pharmaceutical University, 2022, 53(4): 481-489. DOI: 10.11665/j.issn.1000-5048.20220411
Citation: GU Yunshuang, WANG Rui, SU Na, PENG Ying, A Jiye, WANG Guangji, ZHENG Yiwen, SUN Jianguo. Pharmacokinetic study of Erlong Zuoci Pill in rats[J]. Journal of China Pharmaceutical University, 2022, 53(4): 481-489. DOI: 10.11665/j.issn.1000-5048.20220411

耳聋左慈丸在大鼠体内的药代动力学

基金项目: 国家重点研发计划“政府间国际科技创新合作”重点专项资助项目(No.2017YFE0109600);中国医学科学院医学与健康科技创新工程资助项目(No.2021-I2M-5-011)

Pharmacokinetic study of Erlong Zuoci Pill in rats

Funds: This study was supported by the National Key R&D Program "Intergovernmental International Cooperation in Science and Technology Innovation" Key Special Funding Project (No.2017YFE0109600) and the Innovation Fund for Medical Sciences of Chinese Academy of Medical Sciences (No.2021-I2M-5-011)
  • 摘要: 建立大鼠血浆中耳聋左慈丸中成分毛蕊花糖苷、氧化芍药苷、松果菊苷、苯甲酰芍药苷的共检测LC-MS/MS定量方法,并运用此方法评价耳聋左慈丸在大鼠体内的药代动力学行为。采用甲醇作为蛋白沉淀剂,用蛋白沉淀法处理血浆样本,以甲醇为有机相,0.1%甲酸水溶液为水相,在负离子模式下对毛蕊花糖苷、氧化芍药苷、松果菊苷、苯甲酰芍药苷进行定量分析方法的建立,并且对所建方法进行方法学考证。选取健康SD大鼠,单次灌胃20 mL/kg(相当于原药10 g/kg剂量)的耳聋左慈丸提取液,运用建立的方法测定在给药后不同时间间隔的待测物质血浆浓度,并利用Phoenix WinNonlin8.3软件经非房室模型拟合计算药代动力学参数。方法学验证结果表明,毛蕊花糖苷(r = 0.993 7)、氧化芍药苷(r = 0.994 6)在0.5 ~ 50 ng/mL范围内线性良好, 松果菊苷(r = 0.993 6)、苯甲酰芍药苷(r = 0.992 6)在1 ~ 100 ng/mL范围内线性良好,4种物质的批间及批内精密度的RSD均小于15%,批间及批内准确度均在85% ~ 115%之间。提取回收率、基质效应和稳定性均满足相关要求。在大鼠单次灌胃耳聋左慈丸提取液后,4种待测物质都发生了较快的吸收和消除,氧化芍药苷、松果菊苷、苯甲酰芍药苷的血药浓度-时间曲线中都出现双峰现象;与其他3种物质相比,氧化芍药苷在大鼠血浆中浓度较高,cmax1为(24.40 ± 4.78) ng/mL,cmax2为(22.50 ± 2.70) ng/mL。结果表明,该方法的验证结果符合生物样本分析方法指导原则,可用于评价耳聋左慈丸提取液在大鼠体内的药代动力学行为。
    Abstract: To establish a quantitative LC-MS/MS method for the simultaneous detection of components of Erlong Zuoci Pill in rat plasma: verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin, and to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill in rats, plasma samples were purified by protein precipitation using methanol as a protein precipitant.Methanol was used as the organic phase and aqueous solution containing 0.1% formic acid was used as the water phase.The quantitative analysis method of verbascoside, oxypaeoniflorin, echinacoside and benzoylpaeoniflorin was established in negative ion mode, and the validation of bioanalytical method was carried out.Healthy SD rats were selected, and 20 mL/kg (equivalent to the original drug 10 g/kg dose) of Erlong Zuoci Pill extract was administered by intragastric administration.The plasma concentration of the target compounds at different time intervals after administration was determined using the established method, and the pharmacokinetic parameters was calculated by the Phoenix WinNonlin8.3 software using the non-compartmental model.The method validation results showed that verbascoside (r = 0.993 7) and oxypaeoniflorin (r = 0.994 6) had good linear relationship in the concentration range of 0.5-50 ng/mL, echinacoside (r = 0.993 6) and benzoylpaeoniflorin (r = 0.992 6) had good linear relationship in the concentration range of 1-100 ng/mL.The relative standard deviations of the inter- and intra- batch precision of the four compounds were all less than 15%, and the inter- batch and intra- accuracies were between 85% and 115%.Extraction recovery, matrix effect and stability met the relevant requirements.After a single gavage of Erlong Zuoci Pill extract in rats, all the four compounds were rapidly absorbed and eliminated.Oxypaeoniflorin, echinacoside, and benzoylpaeoniflorin showed two peaks in their drug concentration-time curves.Compared with the other three compounds, oxypaeoniflorin has the highest concentration in rat plasma with cmax1 of (24.40 ± 4.78) ng/mL and cmax2 of (22.50 ± 2.70) ng/mL. The results show that the validation results of this method are in line with the guiding principles of biological sample analysis methods, and it can be used to evaluate the pharmacokinetic characteristics of Erlong Zuoci Pill extract in rats.
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出版历程
  • 收稿日期:  2022-04-08
  • 修回日期:  2022-06-13
  • 刊出日期:  2022-08-24

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