Metabolite profiling analysis of plasma, urine, and feces of rats after oral administration of Flos Chrysanthemi Indici preparation through UHPLC-Q-Exactive-MS combined with pharmacokinetic study of markers by UHPLC-QQQ-MS/MS

Zhenju Antihypertensive Tablet is one of the Flos Chrysanthemi Indici preparations (FCIP) with antihypertensive effect. In order to investigate its process in vivo, a method using ultra-high performance liquid chromatography coupled with quadruple Exactive mass spectrometry (UHPLC-Q-Exactive-MS) was established for comprehensive analysis of the absorbed active component and metabolites in rat plasma, urine, and feces after the oral administration of FCIP. As a result, a total of 61 FCIP-related xenobiotics were identified, including 35 in plasma (25 prototypes, 10 metabolites), 40 in urine (23 prototypes, 17 metabolites), and 25 in feces (12 prototypes, 13 metabolites). The metabolism reactions included phase I reactions (such as oxidation, methylation, and reduction) and phase II reactions (such as sulfate conjugation and glucuronide conjugation). Meanwhile, a verified and optimized ultra-performance liquid chromatography with triple quadrupole mass spectrometry (UHPLC-QQQ-MS/MS) method was developed for the simultaneous investigation of the pharmacokinetic profiles of four markers in FCIP. The results showed that all of the four components had good oral absorption effect. This study simultaneously investigated the comprehensive metabolic profiling of FCIP in rat plasma, urine, and feces after the oral administration as well as the four components pharmacokinetic behavior. The results can provide the therapeutic material basis for FCIP.