Recent Progress on Mass Spectrum Based Approaches for Absorption, Distribution, Metabolism, and Excretion Characterization of Traditional Chinese Medicine

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.