Analysis of metabolites of rocuronium bromide in human bile and the study of transmembrane transport mechanism
10.16438/j.0513-4870.2022-0583
- VernacularTitle:罗库溴铵在人胆汁中的代谢产物分析和转运机制研究
- Author:
Ai-nan ZHOU
1
;
Zi-tao GUO
1
;
Jia-jun CHEN
2
;
Yun-quan LUO
2
;
Bo TAN
2
;
Xing-xing DIAO
1
;
Da-fang ZHONG
1
Author Information
1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2. Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
- Publication Type:Research Article
- Keywords:
metabolite;
rocuronium bromide;
human bile;
UHPLC-QE-Orbitrap-MS;
transporter
- From:
Acta Pharmaceutica Sinica
2022;57(8):2461-2470
- CountryChina
- Language:Chinese
-
Abstract:
Rocuronium bromide is an acetylcholine N2 receptor antagonist, which can be used as an auxiliary drug for general anesthesia. It has been reported that rocuronium has two possible metabolic pathways: N-dealkylation and O-deacetylation, which are mainly taken up by liver and excreted by bile in the form of primary drugs. In this paper, the metabolites of rocuronium in human bile were detected by UHPLC-QE-orbitrap-MS, thirteen metabolites were detected, including eleven phase I metabolites and two phase II metabolites, eleven of which had not been previously reported. At the same time, HEK293 cells overexpressing transporter were used to explore the transmembrane transport mechanism of rocuronium, the results showed that rocuronium was the substrate of MATE1, OCT1, OATP1B1 and OATP1B3. The above research results enrich the metabolic pathway of rocuronium in vivo, and put forward the possible transport mechanism of liver uptake and bile excretion, which can better guide the accurate and safe clinical drug application. The collection of human bile samples in this study was approved by the ethics committee of Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Approval Number: 2019-775-130-01).
