Effect of Radix astragali injection on the cytochrome P450 activities with ultrahigh performance-LC-MS/MS in rats
10.13699/j.cnki.1001-6821.2017.16.018
- VernacularTitle:超高效液相色谱-质谱联用法测定黄芪注射液对大鼠细胞色素P450酶活性的影响
- Author:
Hong-Chang YUAN
1
;
Yong-Hao ZHOU
;
Rong LIU
;
Xiao-Kang ZHENG
;
Ke-Li CHEN
;
Nan ZENG
Author Information
1. 成都中医药大学药学院
- Keywords:
Radix astragali injection;
ultrahigh-performance LC-MS/MS;
cytochrome P450;
pharmacokinetics
- From:
The Chinese Journal of Clinical Pharmacology
2017;33(16):1578-1581
- CountryChina
- Language:Chinese
-
Abstract:
Objective To study the effect of Radix astragali injection (RA) on the activities of cytochrome P450 2D6(CYP2D6),2C19,3A4,1A2 and 2C9 by ultrahigh performance-LC and tandem mass spectrome try(UHPLC-MS/MS).Methods The activities of CYP2D6,2C19,3A4,1A2 and 2C9 were evaluated based on pharmacokinetics of metopmlol,omeprazole,midazolam,phenacetin and tolbutamide (five probe drugs) respectively.SD rats were assigned to two groups:control group and experimental group and the rats in the two groups were given 0.9% NaCl and RA 10 mL · kg-1 by intraperitoneal injection for consecutive 7 days respectively.On the 7th day,after intraperitoneal injection for 30 min,a mix dose of five probe drugs was intragastric administration to all rats.Blood samples were collected at different times for UHPLC-MS/MS analysis.Pharmacokinetic parameters of five probe drugs were assessed between the two groups respectively.Results For metoprolol,omeprazole,phenacetin and tolbutamide,the AUG0-t in RA group decreased by 37.8%,55.5%,40.9% and 38.9% respectively,the Cmax in experimental group decreased by 25.4%,33.6%,14.6% and 40.2% respectively.While the AUC0-t and Cmax of midazolam in experimental group increased significandy by 60.1% and 195% respectively.RA could increase the total amount of midazolam absorbed into blood,while decreasing the total amounts of metoprolol,omeprazole,phenacetin and tolbutamide absorbed compared with control group respectively.The method of validation conformed to the requirements of the relevant rat pharmacokinetic guidehnes.Conclusion This method was successfully employed to assess the effect of RA on the activities of CYP2D6,2C19,3A4,1A2 and 2C9 in vivo.RA could inhibit the activity of CYP3A4,while inducing the activities of CYP2D6,2C19,1A2 and 2C9.