Exploration on Interactions of Pharmacokinetics Between Flavonoids and Synephrine in Fructus Aurantii Immaturus Based on UPLC-MS/MS
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±8373.94)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±1381.42)L/kg and(1668.41±394.73)L/kg,significantly lower than(23388.87±6089.53)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.
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