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

Abstract

1. Compound Kushen injection (CKI) is a kind of sterilised 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 19 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 faeces 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, 71 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 characterised. 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 sulphation), and associated combination reactions.

4. The integrated analytical strategy was successfully used to characterise the prototype alkaloids and their metabolites of CKI in vivo, and the results laying a foundation for further study its pharmacodynamic substances.

Keywords:

• UHPLC-ESI-QTOF/MS^E
• Compound Kushen injection
• alkaloids
• metabolic profile
• integrated analysis strategy

Authors’ contributions

Li Zhang participated in data analysis and wrote the manuscript. Ruijuan Li and Ting Zheng participated in animal experiments and data analysis. Huan Wu and Yanyan Yin engaged in study design and supervised study. All authors read and approved the final manuscript.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This study was funded by the National Natural Science Foundation of China (Grant numbers: 81903765); Natural Science Fund of Anhui Provincial Department of Education (Grant numbers: KJ2018A171, 2022AH050444); Natural Science Fund of Anhui Province (Grant numbers: 1908085MH270); Research Fund of Anhui Institute of translational medicine (Grant numbers: 2021zhyx-C18).