中国中药杂志

2021, v.46(02) 444-453

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UPLC-MS/MS快速同时测定犬血浆中补骨脂的10个活性成分及补骨脂犬药代动力学研究
Rapid and simultaneous determination of 10 active components of Psoraleae Fructus in beagle dog plasma using UPLC-MS/MS and its application in pharmacokinetic study

魏蒙蒙;孙学燕;吴思玚;王树瑶;高杨;康琛;杨维;李鹰飞;李川;
WEI Meng-meng;SUN Xue-yan;WU Si-yang;WANG Shu-yao;GAO Yang;KANG Chen;YANG Wei;LI Ying-fei;LI Chuan;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences;State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences;

摘要(Abstract):

建立了同时测定犬血浆中补骨脂的10个活性成分——补骨脂素、异补骨脂素、5,7,4′-三羟基黄酮、5,7,4′-三羟基异黄酮、补骨脂宁、新补骨脂异黄酮、补骨脂甲素、补骨脂二氢黄酮甲醚、补骨脂苷、异补骨脂苷的UPLC-MS/MS分析方法,并对比格犬灌胃给药补骨脂水提取物后不同时间点血浆中的各成分的浓度进行了测定,绘制了血药浓度-时间曲线,并用WinNonlin软件计算了补骨脂活性成分在犬体内的药代动力学特征。液相色谱采用Waters HSS-T3色谱柱(2.1 mm×100 mm,1.8μm);流动相为乙腈-水(含0.004%甲酸),梯度洗脱;质谱检测采用电喷雾离子源,正离子多反应监测模式,分析时间8.5 min。方法学经专属性、准确度、精密度、线性范围、回收率、基质效应和样品稳定性等考察,符合要求,可满足犬灌胃补骨脂提取物后药代动力学研究。犬灌胃给药后,补骨脂10个化学成分的T_(max)为1.92~5.67 h;其中补骨脂素、异补骨脂素、补骨脂苷和异补骨脂苷的C_(max)为383~3 613 ng·mL~(-1),AUC_(0-∞)为3 556~18 949 ng·h·mL~(-1),半衰期t_(1/2)为2.45~4.83 h;其余6个化合物的C_(max)为0.81~19.9 ng·mL~(-1),AUC_(0-∞)为6.54~178 ng·h·mL~(-1),半衰期t_(1/2)为2.95~7.29 h。该研究建立的UPLC-MS/MS分析方法快速、准确、灵敏,适合于比格犬灌胃给药补骨脂提取物后的药代动力学研究,为合理解释中药补骨脂的有效性和毒副作用以及其后续相关研究提供了药代动力学信息。
An UPLC-MS/MS method for rapid and simultaneous determination of psoralen, isopsoralen, apigenin, genistein, bavaisoflavone, neobavaisoflavone, bavachin, bavachinin, psoralenoside, and isopsoralenoside of Psoraleae Fructus in beagle dog plasma was established, and then the method was applied in the pharmacokinetic study after oral administration of Psoraleae Fructus extract to beagle dogs. The pharmacokinetic parameters were calculated by the software of WinNonlin. A Waters HSS-T3 column(2.1 mm×100 mm,1.8 μm)was used for liquid chromatography separation with acetonitrile-water(containing 0.004% formic acid) as the mobile phase for gradient elution.The mass spectrometry was detected using electrospray ion source(ESI) under multi-reaction monitoring mode(MRM), as well as positive ion mode. Analysis time only takes 8.5 min. The methodological study in terms of specificity, accuracy, precision, linear range, recovery, matrix effect, and stability, was validated. The LC-MS analysis method established in this experiment was simple, specific, accurate, reliable, and meet the requirement of pharmacokinetic study in plasma after administration of Psoraleae Fructus extract to beagle dogs. Six beagle dogs received intragastric administration of Psoraleae Fructus extract, T_(max) of 10 chemical components is 1.92-5.67 h; among them, C_(max) of psoralen, isopsoralen, psoralenoside and isopsoralenoside is 383-3 613 ng·mL~(-1), and AUC_(0-∞) is 3 556-18 949 ng·h·mL~(-1), t_(1/2) is 2.45-4.83 h. C_(max) of the remaining six compounds is 0.81-19.9 ng·mL~(-1), AUC_(0-∞ )is 6.54-178 ng·h·mL~(-1), t_(1/2) is 2.95-7.29 h. The UPLC-MS/MS analysis method established in this study was proved to be accurate and sensitive that it can be applied to the pharmacokinetic study of beagle dogs after oral administration of Psoraleae Fructus extract.

关键词(KeyWords): 补骨脂;药代动力学研究;UPLC-MS/MS;同分异构体
Psoraleae Fructus;pharmacokinetic study;UPLC-MS/MS;isomers

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2015ZX09501004-003-005)

作者(Author): 魏蒙蒙;孙学燕;吴思玚;王树瑶;高杨;康琛;杨维;李鹰飞;李川;
WEI Meng-meng;SUN Xue-yan;WU Si-yang;WANG Shu-yao;GAO Yang;KANG Chen;YANG Wei;LI Ying-fei;LI Chuan;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences;State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences;

Email:

DOI: 10.19540/j.cnki.cjcmm.20200629.204

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