川贝母-枇杷叶配伍对枇杷叶中3种黄酮成分血浆药动学的影响

Effect of Drug Pair of Fritillaria Cirrhosa-Eriobotryae Folium on Plasma Pharmacokinetics of Three Flavonoids from Eriobotryae Folium

关键词:  川贝母  枇杷叶  芦丁  槲皮素  山柰酚  高效液相色谱-串联质谱  药动学

Key words:  Fritillaria Cirrhosa  Eriobotryae Folium  rutin  quercetin  kaempferol  HPLC-MS/MS  pharmacokinetics

摘要:

目的 通过高效液相色谱-串联质谱法（LC-MS/MS）方法，探讨川贝与蜜炙枇杷叶配伍后，枇杷叶中芦丁、槲皮素和山柰酚的药动学变化。方法 血浆样品经固相萃取处理。色谱柱为Waters XTerra MS C₁₈柱（150 mm×2.1 mm，3.5 μm）；流动相为乙腈-0.1%甲酸溶液；质谱采用电喷雾离子源，负离子模式（ESI^-），多反应监测模式（MRM）进行定量。大鼠随机分2组，分别灌胃单味枇杷叶和药对川贝-枇杷叶水煎液，测定药动学参数。结果 待测物线性关系良好（r² ≥ 0.998），精密度、准确度、基质效应和提取回收率满足定量要求。与单药组相比，药对组中芦丁、槲皮素和山柰酚的C_max和AUC_0-t均下降，t_1/2推迟。结论 川贝与枇杷叶配伍后，降低了芦丁、槲皮素和山柰酚的最大血药浓度，减慢了消除率，延长了它们在体内的驻留时间。

Abstract:

OBJECTIVE To investigate the effects of the compatibility of Eriobotryae Folium and honey-fried Fritillaria Cirrhosa on pharmacokinetic changes of rutin, quercetin, kaempferol by LC-MS/MS method. METHODS The plasma samples were extracted by solid-phase extraction. The LC column was Waters XTerra MS C₁₈ (150 mm×2.1 mm, 3.5 μm). The mobile phase comprised of acetonitrile and water containing 0.1% formic acid. The quantification was obtained by scanning with multiple reaction monitoring (MRM) via the negative electrospray ionization (ESI^-) source. The rats were randomly divided into two groups and orally administered with Eriobotryae Folium or Eriobotryae Folium-Fritillaria Cirrhosa decoction. RESULTS The correlation coefficients were over 0.998, indicating excellent linearity. The values of precision, accuracy, matrix effect and average recovery were acceptable. Compared with single herb group, the C_max and AUC_0-t were decreased, the t_1/2 were extended in herbal pair group. CONCLUSION After combining the herbs, the bioavailability of rutin, quercetin and kaempferol are reduced, the elimination of them delays, and the dwell time increases.