Affiliation:
1. Fujian Provincial Key Laboratory of Innovative Drug Target Research and State Key Laboratory of Cellular Stress Biology, School of Pharmaceutical Sciences, Xiamen University, Xiamen 361102, China
2. The First Affiliated Hospital of Xiamen University, Xiamen 361003, China
3. School of Medicine, Xiamen University, Xiamen 361102, China
4. MassDefect Technologies, NJ 08540, USA
Abstract
Background:
The absorption, distribution, metabolism, and excretion (ADME) of traditional Chinese
medicine (TCM) components are closely related to their therapeutic efficacy, toxic effects, and drug interactions.
Based on the study of the whole process of ADME in TCM, it is important to screen out the key pharmacokinetic
index components (pharmacokinetics PK/toxicokinetics TK makers), which can be beneficial for their clinical application
or drug development. Although the detection of traditional small molecular drug’s in vivo ADME process can
be achieved by radioisotope methods, this approach might not be useful for the case of TCM. In detail, it is very
difficult to label and trace each component in complex Chinese medicine, while it is also difficult to accurately follow
the position of tracer in the whole in vivo process. In short, it is a tough task to obtain the ADME information of
Chinese medicine, especially in the case of a clinical study.
Methods:
We searched several scientific databases, including Pubmed, ACS, ScienceDirect, Springer, Wiley, etc., by
using “Chinese medicine” and “in vivo metabolism” as keywords. By summarizing the current reports as well as our
recent progress in this field, this review aims to summarize current research methods and strategies for ADME study
of TCM based on high-resolution mass spectrometry-based data acquisition and data mining technology which is an
important approach but has not been systematically reviewed.
Results:
With the development of various hybrid tandem high-resolution mass spectrometry (Q-TOF, LTQ FT,
Q-Exactive), liquid chromatography-high resolution mass spectrometry (LC-HRMS) has become the mainstream
method in studying ADME process of TCM. This review aims to comprehensively summarize current research technologies
and strategies based on high-resolution mass spectrometry, with emphasis on the following three aspects:
(1) comprehensive and automatic acquisition technologies for the analysis of in vivo TCM components (i.e., BEDDA);
(2) quick and comprehensive identification techniques for analyzing in vivo chemical substances and metabolites
of TCM (i.e., PATBS or metabolomic analysis); (3) efficient correlation determination between in vivo or in
vitro compounds and their metabolic transformation (i.e., MTSF).
Conclusion:
To the best of our knowledge, this is a pioneering review for systematically summarizing the analysis
methods and strategies of ADME in TCM, which can help understand the whole ADME process, therapeutic molecular
basis, or toxic substances of TCM. Furthermore, this review can also provide a feasible strategy to screen out
PK/TK markers of TCM, while this information can be helpful to elucidate the pharmacodynamics or toxicity mechanisms
of Chinese medicines and be useful in their future drug development. At the same time, we also hope that this
review can provide ideas for further improvement of TCM analysis methods and help rational clinical use of TCM
and the development of new drugs.
Funder
National Natural Science Foundation of China
National Major Scientific and Technological Special Project for “Significant New Drugs Development”
Fundamental Research Funds for the Central Universities
Publisher
Bentham Science Publishers Ltd.
Subject
Clinical Biochemistry,Pharmacology
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献