Quality Control of Chinese Medicines

Quality control is the key for modernization and internationalization of traditional Chinese medicines (TCMs). Besides techniques, key scientific issues in research on quality control of TCMs are crucial for well understanding TCMs. In this chapter, science including the principles for optimization of quality markers and alternative reference compounds were reviewed and discussed.

Polysaccharides with multiple biological activities are usually considered as one of the major bioactive compounds in Chinese medicines (CMs). At present, the development of drugs and functional foods related to polysaccharides has attracted a great deal of attention due to their great potential effects and diverse action mechanisms. However, quality control of polysaccharides is the bottleneck and challenge due to their complexity and chemical diversity. Actually, the bioactivities of polysaccharides are closely related to their molecular structures. In order to ensure their safety and efficacy, the development of novel approaches based on the molecular structures for the improvement of quality control of polysaccharides is significantly important. Therefore, in this article, the relationship between biological activities and chemical structures, as well as the action mechanisms of polysaccharides from CMs were summarized first. Furthermore, saccharide mapping, a novel strategy for quality control of bioactive polysaccharides from CMs, was introduced and the application and perspectives were also discussed.

Due to the complex compositions of Chinese medicine (CM), how to rapidly and efficiently discovery the biologically active components from them is a huge challenge. Traditionally, tedious extraction-isolation-purification-(bio)assay procedures are usually involved in the lead compounds discovery from them, resulting in a large amount of raw material, organic solvents, time and labor consumption, and the major chemical degradation risks of the unstable compounds. The fortunate thing is that with the rapid technological development of chromatographic separation, compound identification, and (bio)assay, two emerging strategies including functional-base screening and affinity-based screening have been developed for rapid profiling and distinguish individual active components from CM in the past two decades. The research status of screening strategies for active ingredients of CM was reviewed, and the online chromatographic screening and analysis methods for active ingredients were emphatically introduced.

In this chapter, the principles and processes of bio-specific extraction/receptor fishing, such as equilibrium dialysis, centrifugation, and material-based ligand screening assay, are briefly introduced, respectively. All these screening methods have been proven to be effective, and each method has its advantages and disadvantages in terms of complexity, time spending, solvent consumption, equipment, and labor-intensiveness. Then, the major emphases are focused on summarizing and discussing the reported various types of biomaterials, such as enzymes, receptors, cell membranes, and living cells, for the screening of active components in Chinese medicines. The trends of applications of bio-specific extraction/receptor fishing in the screening of active components were also discussed.

Active ingredients discovery has always been a hot topic for the research of Chinese medicines (CMs). The component-effect relationship is one of the widely used strategies for finding herbal active ingredients. This article systematically reviewed component-effect relationship analysis in the application of active components discovery in CMs, including sampling and sample preparation, chemical fingerprint establishment, pharmacological effect evaluation, and component-effect relationship analysis. The challenges to this method, such as the effects of dose–response relationship, data normalization, and the relationship analysis methods, were also discussed, which is helpful to well understand the method and improve the research quality.

Traditional Chinese medicines (TCMs) were applied to treat various biological diseases with a long history. TCMs are characterized by multiple components corresponding to abundant targets and holistic effects in body. The network pharmacology, as a constructive technology integrating multiple sources of information, not only considers the pharmacology response of TCMs in cellular or phenotypic levels, but also reflects the characterization of chemical material basis in TCMs. It is very crucial to fully consider the source of chemical components representing the whole TCM for expanding its network pharmacology research. More persuasive multi-component network pharmacology would be conducive to elucidate the quality control and therapeutic mechanism of TCMs.

Traditional Chinese medicine (TCM) plays a vital role in the prevention and treatment of various diseases for thousands of years. It is of great significance to elucidate the effective material basis and related action mechanism for promoting the modernization of TCM, as well as the research and development of innovative Chinese medicine. Virtual screening is also called computer-aided screening, that is, compound molecules are pre-screened on the computer with a suitable algorithm before biological activity screening, in order to reduce the actual number of screened compounds and improve the discovery efficiency of lead compounds. Recently, molecular docking-based virtual screening techniques had been applied for discovering active ingredients in Chinese medicine. This chapter introduces the research strategies and related technologies of molecular docking, including chemoinformatics and bioinformatics, principle and basic protocols of molecular docking, as well as the application of molecular docking in the discovery of active ingredients.

Elucidating the effective constituents of Chinese medicine (CM) is a big challenge due to its complex constituents and diverse interactions. Knock-out/knock-in technique is a promising strategy to reveal the integrative components that contribute to effect of CM. When the target components are knocked out from the complete sample, the bio-effect alterations before and after the target components being knocked out can reflect the contribution of the target components to the effect of CM. By knocking various concentrations of target components in the negative sample, a content-efficacy relationship can be constructed for the quality control of CM. In this chapter, we summarized the concept, current status and perspectives of knock-out/knock-in technique in the form of a case study to provide a reference for the quality control of CM.

Sample preparation is an important and time-consuming step in quality control of herbal medicine. Due to the state of most solid samples, their constituents should be transferred to solvents from the matrix before analysis. One of the traditional sample preparation techniques is called “solid–liquid extraction”. The classical solid–liquid extraction methods include decoction, reflux extraction, steam distillation, Soxhlet extraction, and ultrasonic-assisted extraction. Those classical extraction methods are even more widely used in routine quality control of herbal medicines than some modern extraction methods due to low investment in equipment and easy operation. In this paper, the classical extraction methods used for sample preparation in quality control are summarized, which may provide some ideas for the development of new quality control methods for herbal medicine in the future.

For many bioactive chemicals contained in traditional Chinese medicines, pressurized liquid extraction has become a preferred green extraction method. This review goes over the extraction principles and how to improve the extraction efficiency by optimizing the extraction parameters. The use of various solvent combinations and other extraction additives to improve extraction efficiency is explored. The utilization of combined and hyphenated sample preparation and analytical procedures, as well as the dynamic mode of extraction in pressurized liquid extraction, are discussed. This review also summarized applications that used pressurized liquid extraction to enrich different functional components from medicinal herbs.

Traditional Chinese medicine (TCMs), as an important branch of medicine, has been used in the treatment of various diseases in East Asia for thousands of years. However, due to the complexity of TCMs, the development of quality control methods has always been regarded as a challenging and important factor in their modernization and globalization. Among the procedures involved in the quality control of TCMs, extraction is the first and most critical step. Analysis of an improper treated sample may result in poor quality of analytical data. As a new green extraction technology, supercritical fluid extraction (SFE) has gained increasing interest due to its selective extraction, low operation cost, short processing time, and less impact on the environment, compared to that of most conventional extraction methods. The selectivity and yield of the target compounds can be adjusted by optimizing of the process parameters, especially the temperature, pressure, and modifiers based on method design. Following the extraction, an adequate evaluation based on the identification, quantity, and bioactive analysis of the compounds present in the extract is necessary for the quality control of TCMs. Phytochemical profiling tools such as GC, LC, SFC, and their online methods applied to identify and quantify these bioactive compounds are discussed. In this article, the basic principles, methods, instruments, and main characteristics and application of SFE in quality control of TCMs in the past five years are reviewed.

Thin-layer chromatography is a conventional analytical method in quality control of traditional Chinese medicines. Many advantageous characteristics make it an important technology in quality research. However, with the continuous updating of many technologies, the application status and development trend of TLC also reflect some limitations. This paper summarizes the research advances in TLC in terms of active ingredient discovery, qualitative and quantitative analysis and current technological development, aiming to provide a reference for the in-depth study of TLC in the quality control research of traditional Chinese medicine.

Infrared spectra of solid, liquid, and gas samples can be measured without separation or extraction. Most organic and inorganic molecules can generate fingerprint-like infrared spectral signals without derivation or labeling. As a result, infrared spectroscopy can directly characterize the holistic compositions of Chinese medicinal samples in their entirety. The directness of infrared spectroscopy brings the advantages of integrality and simplicity. On one hand, infrared spectroscopy can simultaneously profile inorganic molecules, organic small molecules, and macromolecules in one sample. This integrality advantage helps to control the unknown and unexpected ingredients that may contribute to the efficacy and safety of Chinese medicine. On the other hand, the chemical analysis and quality assessment by infrared spectroscopy can be performed quickly, on-site and on-line. This simplicity advantage helps to achieve the high-efficiency and low-cost quality control of Chinese medicine. The fundamental principles and methods of infrared spectroscopy for quality control of Chinese medicine were discussed in this article.

Gas chromatography (GC) is a well-known and widely employed technique for separation and analysis of the gaseous and volatile components. Modern GC technique was firstly invented by James and Martin in 1952 and applied for the separation of amino acids. After decades of development, GC has large number of applications in a variety of fields due to its high efficiency and great sensitivity, especially for the research of Chinese herbal medicine including the determination and characterization of bioactive compounds such as volatile oils, fingerprint analysis of holistic quality control, pharmacokinetics research and metabolomics analysis. In addition, GC and GC-MS have also been adopted and are now used for an increasingly growing list of applications in other various fields, such as environmental analysis, food and beverage analysis and so on.

Active compounds derived from Chinese medicines (CMs) have already illustrated immense therapeutic potential over an array of different diseases, and served as an inexhausted source for drug discovery and development. With the continuous development of the instrumentation’s capabilities as far as detection and separation is concerned, analytical methods for these components have come into the spotlight. Based on the extra sensitivity, specificity, and good separation in complex samples, HPLC and LC–MS have been the ultimate tool in the qualitative and quantitative tools for the determination of different types of chemical compounds. Herein, we focus on the achievements in qualitative and quantitative analysis of the major classes of phytochemicals (flavonoids, alkaloids, saponins, terpenoids, and carbohydrates) in CMs through HPLC and LC–MS.

Quality control of Chinese medicines (CMs) is a difficult work because of their intrinsic complexity. UPLC-MS is at the forefront of this crucial challenge due to its prominent performance in qualitative and quantitative analysis. This chapter aims to explain UPLC-MS-based methodologies in the field of quality control for CMs, covering the basic principles of various instruments, and their specific applications in the characterization of chemical composition, screening, and quantification of chemical markers. Meanwhile, a description of some universal or integrated strategies (e.g., fingerprints, chemical markers’ knock-out, multivariate statistical analysis and quantitative analysis of multi-components by single marker) are also provided.

Analysis of active components or dubious adulterants in Chinese medicines is often somewhat problematic due to the highly complex nature of the sample matrices, which makes the identification of individual constituents extremely challenging. Capillary electrophoresis (CE) includes different separation modes and detections, allowing many versatile applications in the analysis and quality control of Chinese medicines. The use of mass spectrometry (MS) as an advanced detection technique is inevitable in the evolution of various current separation methods, which is particularly true for a CE separation. The addition of MS detection can provide specific and more sensitive identification of the analytes in such complex and challenging matrices. Combined with the development of MS detection and CE separation techniques, the new configuration forms a powerful analytical tool for the speedy and accurate identification and quantification of various constituents in Chinese medicines. In order to provide some substantial evidence to consider using CE as an alternative method for Chinese medicine analyses, this chapter covers some essential theoretical aspects of CE separation and different detection methodologies, with specific emphasis on CE-MS. Although by no means comprehensive, it is intended to provide a brief description of CE and CE-MS techniques, which is related to the consideration of using these analytical approaches as promising techniques for Chinese medicine analyses. Succinctly, this chapter is devoted to providing some details of CE and CE-MS method developments and further applications of the developed methods in Chinese medicine analyses. The most critical applications of CE and CE-MS cited in ISI Web of Science and publisher databases are presented in a tabular format. The readers can, therefore rapidly find the existing CE and CE-MS analytical techniques in the Chinese medicine field. Furthermore, on the basis of previous studies, it can be concluded that the CE analytical approach has great potential to be used for routine quality control of Chinese medicines. Finally, the main challenges and future prospects for a widespread application of CE and CE-MS in the Chinese medicine industry are discussed.

The scope of the chapter is based on surveys with a total of >1000 responses. So, the scope of this chapter focuses on certain specific requirements from the global qNMR community. Specifically, this chapter originated as an attempt to collect the most interesting facts about qNMR principles, strategies, best practices, and existing applications, as seen by qNMR scientists today. Some sections are simple enough to be understood by a college student, whereas others will require some concentration and study to be completely understood. To advance qNMR applications in Chinese Medicine, a holistic review summarized possible qNMR strategies used in quality control of Chinese Medicine in the past ten years. It is hoped, however, that this information could inspire readers to study the secrets of qNMR technology and to utilize the tools presented in this chapter to find their own qNMR applications in the near future.

The quality of Chinese medicines (CMs) is the basis to guarantee the clinical safety, effectiveness, and controllability of medicinal materials. It is the lifeline to promoting sustainable development of the CM industry. The research and application of quality evaluation methods is a national strategic issue related to the scientific and industrial development of CMs. Recent progress in computational methods and high throughput technologies makes it possible to comprehend CM molecular and systematic levels. Especially in recent years, a new era of omics has emerged, opening an exciting and fertile area to investigate the holistic change and quality evaluation of CMs. This review summarizes the current research advances of omics in the quality evaluation of CMs and concludes with an outlook on future trends and opportunities for omics research in CMs. In particular, the role of omics according to different factors affecting the quality of CMs, such as origin, medicinal part, producing area, cultivation pattern, harvest time, growth stage, and processing method, have been highlighted. This review would lay a foundation for the accurate evaluation of CM quality and further improve the quality standards of CMs.

The modernization and globalization of traditional Chinese medicines (TCMs) require the implementation of a robust quality control system, and the application of modern theories and technologies in analytical chemistry can greatly facilitate the establishment of such a system. However, inherent “uncertainties” are often present in the chemical measurement data obtained from TCMs using modern analytical instruments. To address this issue, the utilization and further development of Chemometrics are urgently needed. It plays a crucial role in reducing or eliminating the “uncertainties” associated with the chemical composition, structure, and other relevant information of the TCMs, primarily focusing on qualitative identification and quantitative determination. Given that TCMs are complex multi-component systems, future quality evaluation may encompass in silico prediction of physical/chemical properties and activities. Furthermore, it is essential to establish a link between the measured data and biological activity. Achieving these objectives necessitates continuous advancements in Chemometrics and close collaboration with artificial intelligence. In essence, the quality control of TCMs requires extensive knowledge of Chemometrics, both existing and yet to be explored. This chapter provides a comprehensive discussion on various topics, including “sampling for analytical purposes,” “experimental design and optimization,” “evaluation of experimental measurements,” “fingerprint pre-processing,” “multivariate calibration and multivariate resolution,” “pattern recognition of fingerprint data,” “fingerprint-efficacy modeling,” “structure–property/activity relationship,” and “expert system of TCMs fingerprint.”