UPLC-MS/MS法及体外溶出/吸收仿生系统法对异欧前胡素药代动力学特征的研究
Pharmacokinetic study of isoimperatorin in rats using UPLC-MS/MS and a drug dissolution/absorption simulating system
目的 研究中药白芷中主要成分异欧前胡素体内药代动力学特征及生理因素对其体内过程的影响。方法 建立超高效液相色谱质谱联用方法（UPLC-MS/MS），测定灌胃给药后大鼠血浆中异欧前胡素血药浓度变化，同时考察异欧前胡素在不同pH下的稳定性以及采用体外方法考察异欧前胡素的溶出性能；结果 建立了UPLC-MS/MS 法测定大鼠血浆中的异欧前胡素浓度，并用于其药代动力学研究。质谱条件：采用电喷雾离子源（ESI），正离子检测，监测离子为271.02→202.9（异欧前胡素）和216.9→173.7（佛手柑内酯，内标），该方法准确度、精密度、回收率、线性范围皆符合要求；经非房室模型拟合后其数据表明异欧前胡素在体内分布广泛（Vz/F = 543.7 ± 4.79 L/kg）、血药浓度水平低（Cmax = 0.26 ± 0.002 μg/mL）、代谢慢；在酸性和碱性溶液中异欧前胡素均不稳定、发生降解；溶出实验表明异欧前胡素溶出缓慢，水溶性差（累积溶出率=0.046±0.02%）；结论 建立的UPLC-MS/MS方法专属性强，灵敏度高，可用于异欧前胡素的体内定量分析；以及白芷中有效成分异欧前胡素在体内血药浓度低，可能由于其在胃酸溶液中不稳定、胃肠道中溶出量少所导致。
pharmacokinetic study of isoimperatorin (IO), one of the major bioactive ingredients in the herb, Angelicae dahuricae, was performed in rats (n = 10) using a newly developed ultra-performance liquid chromatography-tandem mass spectrometry method. Tandem mass spectrometry was performed and the protonated parent→daughter ion pairs at m/z 271.02→202.9 for IO and m/z 216.9→173.7 for the internal standard, bergapten, were monitored. The analysis was validated with respect to linearity, recovery, specificity, accuracy, and precision. The pharmacokinetic parameters were obtained by non-compartmental analysis. After administration, IO was extensively distributed and rapidly eliminated from the plasma. The parameters also indicate a lower IO plasma concentration and poor absorption. Factors that led to this result were the instability of IO in acidic and basic conditions, poor solubility, and low dissolution rate. The stability of IO was observed at different pH levels using high-performance liquid chromatography, and the solubility at physiological conditions was determined using a novel drug dissolution/absorption simulating system.
俸珊、李超、何新
药学医学研究方法中医学
异欧前胡素白芷体外药物溶出/吸收仿生系统（DDASS）UPLC-MS/MS
IsoimperatorinAngelicae dahuricae radixin vitro modelsUPLC-MS/MS
俸珊,李超,何新.UPLC-MS/MS法及体外溶出/吸收仿生系统法对异欧前胡素药代动力学特征的研究[EB/OL].(2011-06-10)[2025-08-16].http://www.paper.edu.cn/releasepaper/content/201106-199.点此复制
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