Analysis of Bioactive Components, Simultaneous Determination and Pharmacokinetic Study of Six Components After Intragastric Administration of Qiling Wenshen Xiaonang Granule.

Background: Qiling Wenshen Xiaonang Granule (QLWSG), a compound preparation of traditional Chinese medicine, which was recently approved by the National Medical Products Administration for clinical trials of polycystic ovary syndrome (PCOS). It is necessary to do further researches about QLWSG for better understanding. Methods: In this study, qualitative and quantitative analysis of QLWSG in rat plasma were conducted by ultra-fast liquid chromatography coupled with triple quadrupole mass spectrometry (UFLC-QqQ-MS). The multi-reaction monitoring mode/electrospray ionization source of the triple quadrupole mass spectrometer was used for detection. The plasma samples were prepared by precipitating protein with organic solvent. Results: 21 prototypes in rat plasma were identified after intragastric administration of QLWSG, and most of the identified components are flavonoids and phenolic acids. Furthermore, a sensitive and specific UFLC-QqQ-MS method was also built, which was used for simultaneous determination and pharmacokinetic study of six active components, astragaloside IV, calycosin, calycosin-7-O-β-D-glucoside, icariin, epimedin C and rosmarinic acid in rat plasma after intragastric administration of QLWSG with three doses (8, 16, 24 g/kg). All the calibration curves showed good linearity (r > 0.9942) in the range of concentration measured. The validated method is stable and reliable, meanwhile, successfully applied for pharmacokinetic evaluation of tested compounds. The results showed that there was no significant difference in half-lives (t 1/2 ) and clearance (CL/F) of six analytes at the three doses were observed. Conclusions: It can be inferred that the pharmacokinetic behavior of QLWSG is positively correlated to dose at the range of 8–24 g/kg. Simultaneous determination of the six compounds in vivo for the first time by UFLC-QqQ-MS. The validated method and the results of this study would benefit therapeutic material basis and clinical application for QLWSG. And the validated method would also be applied to the analysis of other Chinese medicine compound prescriptions.