目的 建立UPLC-MS-MS生物樣品分析方法，同時(shí)測(cè)定大鼠血漿中小檗堿、柚皮苷、橙皮苷與新橙皮苷，測(cè)定SD大鼠ig小檗堿和枳實(shí)提取物后血藥濃度及相關(guān)藥動(dòng)學(xué)參數(shù)的變化。方法 以UPLC Acquity BEH C18 （50 mm×2.1 mm，1.7μm）為色譜柱，含0.05%甲酸2 mmol/L甲酸銨水（水相A）-含0.05%甲酸乙腈（有機(jī)相B）為流動(dòng)相梯度洗脫；SD大鼠分為ig小檗堿組、枳實(shí)提取物組、小檗堿和枳實(shí)提取物配伍組。結(jié)果 UPLC-MS/MS可快速分析血漿樣品中小檗堿、柚皮苷、橙皮苷與新橙皮苷，方法學(xué)驗(yàn)證符合生物樣品分析方法要求；SD大鼠ig小檗堿與枳實(shí)提取物配伍后，小檗堿血藥濃度較單給小檗堿組明顯提高，生物利用度明顯提高；同時(shí)大鼠血漿中可檢測(cè)到柚皮苷與新橙皮苷。結(jié)論 SD大鼠給藥小檗堿后，枳實(shí)黃酮的生物利用度明顯提高，提示小檗堿與枳實(shí)黃酮有明顯的藥物相互作用。

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.

國(guó)家重大新藥創(chuàng)制專項(xiàng)資助（2011ZX09102-011-08）；國(guó)家自然科學(xué)基金應(yīng)急管理項(xiàng)目（81541083）