An integrated analytical strategy to decipher the metabolic profile of alkaloids in Compound Kushen injection based on UHPLC-ESI-QTOF/MS E .

1. Compound Kushen injection (CKI) is a kind of sterilized water-soluble traditional Chinese medicine preparation that has been used for the clinical treatment of a variety of cancers (hepatocellular carcinoma, lung cancer, etc.) for nineteen years. However, to date, the metabolism-related study on CKI in vivo has not been conducted.2. An integrated analytical strategy was established to investigate the metabolic profile of alkaloids of CKI in rat plasma, urine and feces based on ultra-high performance liquid chromatography-electrospray quadrupole time-of-flight mass spectrometry in MS E mode (UHPLC-ESI-QTOF/MS E ).3. Nineteen prototype alkaloids (including 12 matrine-type alkaloids, 2 cytisine-type alkaloids, 3 lupinine-type alkaloids, and 2 aloperine-type alkaloids) of CKI were identified in vivo . Furthermore, seventy-one metabolites of alkaloids (including 11 of lupanine-related metabolites, 14 of sophoridine-related metabolites, 14 of lamprolobine-related metabolites and 32 of baptifoline-related metabolites) were tentatively characterized. Metabolic pathways involved in the metabolism of phase I (include oxidation, reduction, hydrolysis, and desaturation), phase II (mainly include glucuronidation, acetylcysteine or cysteine conjugation, methylation, acetylation and sulfation) and associated combination reactions.4. The integrated analytical strategy was successfully used to characterize the prototype alkaloids and their metabolites in CKI, and the results laying a foundation for further study its pharmacodynamic substances in vivo .