基于UPLC-MS/MS探讨枳实中黄酮类化合物与辛弗林药动学的相互影响  

Exploration on Interactions of Pharmacokinetics Between Flavonoids and Synephrine in Fructus Aurantii Immaturus Based on UPLC-MS/MS

作　　者：张硕 徐俊达 石敬依 蔡文君 刘长利[1] 罗容[1] ZHANG Shuo;XU Junda;SHI Jingyi;CAI Wenjun;LIU Changli;LUO Rong(School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China;Dept.of Drug Administration,Market Supervision and Administration of Shijingshan District,Beijing 100041,China;Dept.of Pharmacy,Beijing Longfu Hospital,Beijing 100010,China;Dept.of Pharmacy,Peking University First Hospital,Beijing 100034,China)

机构地区：[1]首都医科大学中医药学院,北京100069 [2]北京市石景山区市场监督管理局药品监管科,北京100041 [3]北京市隆福医院药剂科,北京100010 [4]北京大学第一医院药剂科,北京100034

出　　处：《中国医院用药评价与分析》2024年第6期641-646,650,共7页Evaluation and Analysis of Drug-use in Hospitals of China

基　　金：国家自然科学基金面上项目(No.81973431)。

摘　　要：目的:基于超高效液相色谱-三重四级杆串联质谱(UPLC-MS/MS),探讨枳实中黄酮类化合物与辛弗林药动学的相互影响,为引入黄酮类化合物作为枳实的质量定量控制指标提供科学依据。方法:取24只SD大鼠,随机分为6组(n=4),A组为辛弗林+6种黄酮类化合物(新橙皮苷、柚皮苷、芸香柚皮苷、橙皮苷、川陈皮素和野漆树苷),B组为辛弗林单独给药,C组为辛弗林+柚皮苷,D组为辛弗林+新橙皮苷,E组为6种黄酮类化合物单独给药,F组采用等体积的0.9%氯化钠溶液处理,均灌胃给药。取给药后不同时间点的血浆,测定血浆中柚皮苷、新橙皮苷和辛弗林含量,应用DAS 2.0软件计算药动学参数。利用UPLC-MS/MS方法测定血药浓度。结果:A组大鼠新橙皮苷清除率为(9337.88±8373.94)L/h·kg,显著高于E组的(2558.22±610.87)L/h·kg,差异有统计学意义(P<0.05)。A组、D组大鼠新橙皮苷的分布体积分别为(2549.72±1381.42)、(1668.41±394.73)L/kg,均明显低于E组的(23388.87±6089.53)L/kg,差异均有统计学意义(P<0.05)。A组大鼠辛弗林的平均停留时间为(2.50±0.63)h,较B组、C组和D组[(1.62±0.11)、(1.70±0.17)和(1.57±0.08)h]更长,差异均有统计学意义(P<0.05)。结论:辛弗林对新橙皮苷的消除率和分布影响较大,枳实中的黄酮类化合物可延长辛弗林的平均停留时间。OBJECTIVE:To probe int the interactions of pharmacokinetics between flavonoids and synephrine in fructus aurantii immaturus based on ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry(UPLC-MS/MS),so as to provide scientific basis for the introduction of flavonoids as a quality and quantitative control index of fructus aurantii immaturus.METHODS:A total of 24 SD rats were extracted to be randomly divided into six groups(n=4),group A was administrated with synephrine+six kinds of categories of flavonoids(neohesperidin,naringin,narirutin,hesperidin,nobiletin and rhoifolin),group B was administrated with synephrine alone,group C was administrated with synephrine+naringin,group D was administrated with synephrine+neohesperidin,group E was administrated with six categories of flavonoids alone,group F was administrated with an equal volume of 0.9%NaCl solution,all administered by gavage.The plasma was taken at different time points after administration,the contents of naringin,neohesperidin and synephrine in plasma were determined,and DAS 2.0 software was used to calculate the pharmacokinetic parameters.The blood concentration was determined by using UPLC-MS/MS method.RESULTS:Clearance rate of neohesperidin in group A was(9337.88±8,373.94)L/h·kg,significantly higher than(2558.22±610.87)L/h·kg in group E,with statistically significant difference(P<0.05).The distribution volume of neohesperidin in group A and group D were respectively(2549.72±1,381.42)L/kg and(1668.41±394.73)L/kg,significantly lower than(23388.87±6,089.53)L/kg in group E,with statistically significant differences(P<0.05).The mean detention time of synephrine in group A was(2.50±0.63)h,in comparison with[(1.62±0.11)h,(1.70±0.17)h and(1.57±0.08)h]of groups B,C and D,the differences were all statistically significant(P<0.05).CONCLUSIONS:Synephrine has great effect on the clearance rate and distribution of neohesperidin,and the flavonoids in fructus aurantii immaturus can prolong the mean detention time of synephrine

关 键 词：枳实 黄酮类化合物 辛弗林 药动学 

分 类 号：R932[医药卫生—生药学] R969.1[医药卫生—药学]