目的 建立UPLC-MS-MS生物样品分析方法，同时测定大鼠血浆中小檗碱、柚皮苷、橙皮苷与新橙皮苷，测定SD大鼠ig小檗碱和枳实提取物后血药浓度及相关药动学参数的变化。方法 以UPLC Acquity BEH C18 （50 mm×2.1 mm，1.7μm）为色谱柱，含0.05%甲酸2 mmol/L甲酸铵水（水相A）-含0.05%甲酸乙腈（有机相B）为流动相梯度洗脱；SD大鼠分为ig小檗碱组、枳实提取物组、小檗碱和枳实提取物配伍组。结果 UPLC-MS/MS可快速分析血浆样品中小檗碱、柚皮苷、橙皮苷与新橙皮苷，方法学验证符合生物样品分析方法要求；SD大鼠ig小檗碱与枳实提取物配伍后，小檗碱血药浓度较单给小檗碱组明显提高，生物利用度明显提高；同时大鼠血浆中可检测到柚皮苷与新橙皮苷。结论 SD大鼠给药小檗碱后，枳实黄酮的生物利用度明显提高，提示小檗碱与枳实黄酮有明显的药物相互作用。

Objective UPLC-MS/MS bio-analysis method was developed for the simultaneous determination of berberine, naringin, hesperidin, and neohesperidin in plasma of rats. Methods UPLC Acquity BEH C₁₈ (50 mm × 2.1 mm, 1.7 μm) column was used, mobile phases were containing 0.05% formic acid and 2 mmol/L ammonium formate in water (A)-containing 0.05% formic acid in acetonitrile (B) as the mobile phase gradient elution; SD rats were randomly divided into oral administration berberine group, Citrus aurantium extract group, and berberine and C. aurantium extract compatibility group. Results UPLC-MS/MS method could be applied to determination of berberine, naringin, hesperidin, and neohesperidin, method validation meets the requirements of biological sample analysis. When rats were administered with berberine and C. aurantium extract compatibility, the plasma concentration of berberine was much more than single dose of berberine group and the bioavailability of berberine was increased. Meanwhile, naringin and neohesperidin can be detected in rat's plasma. Conclusion The bioavailability of flavonoids is significantly improved as well compared to the single dose of C. aurantium extract. This suggests that berberine and C. aurantium extract compatibility has significant drug-drug interaction.

国家重大新药创制专项资助（2011ZX09102-011-08）；国家自然科学基金应急管理项目（81541083）