Development of chromatographic technologies for the quality control of Traditional Chinese Medicine in the Chinese Pharmacopoeia

As an important branch of medicine, Traditional Chinese Medicine(TCM) has been applied for the treatment of diseases for thousands of years in China and other countries in East Asia. The Chinese Pharmacopoeia(ChP) is a drug code formulated by the Chinese government, and it includes a special volume for the monographs of TCM, which plays an important role in ensuring the quality of drugs. The use of quality control technology has always been a complex and important factor in TCM. Owing to the chemical diversity of TCM, chromatography technology has been proven to be a comprehensive strategy for the assessment of the overall quality of TCM and has become the main analytical method in the ChP.This article provides an overview of the classical and modern chromatographic technologies applied in the ChP, and summarizes the advantages and disadvantages of each technique in the TCM monographs.In 2020, the new edition of the Ch P(the 2020 edition) has been implemented at the end of 2020. This paper also contains a brief introduction about the application of chromatographic technologies in the new edition of the ChP.

Construction of Inorganic Elemental Fingerprint and Multivariate Statistical Analysis of Marine Traditional Chinese Medicine Meretricis concha from Rushan Bay

Meretricis concha is a kind of marine traditional Chinese medicine(TCM), and has been commonly used for the treatment of asthma and scald burns. In order to investigate the relationship between the inorganic elemental fingerprint and the geographical origin identification of Meretricis concha, the elemental contents of M. concha from five sampling points in Rushan Bay have been determined by means of inductively coupled plasma optical emission spectrometry(ICP-OES). Based on the contents of 14 inorganic elements(Al, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se, and Zn), the inorganic elemental fingerprint which well reflects the elemental characteristics was constructed. All the data from the five sampling points were discriminated with accuracy through hierarchical cluster analysis(HCA) and principle component analysis(PCA), indicating that a four-factor model which could explain approximately 80% of the detection data was established, and the elements Al, As, Cd, Cu, Ni and Pb could be viewed as the characteristic elements. This investigation suggests that the inorganic elemental fingerprint combined with multivariate statistical analysis is a promising method for verifying the geographical origin of M. concha, and this strategy should be valuable for the authenticity discrimination of some marine TCM.

Inorganic Elemental Determinations of Marine Traditional Chinese Medicine Meretricis concha from Jiaozhou Bay:The construction of Inorganic Elemental Fingerprint Based on Chemometric Analysis

The goal of this paper is to explore the relationship between the inorganic elemental fingerprint and the geographical origin identification ofMeretricis concha, which is a commonly used marine traditional Chinese medicine （TCM） for the treatment of asthma and scald bums. For that, the inorganic elemental contents ofMeretricis concha from five sampling points in Jiaozhou Bay have been determined by means of inductively coupled plasma optical emission spectrometry, and the comparative investigations based on the contents of 14 inorganic elements （A1, As, Cd, Co, Cr, Cu, Fe, Hg, Mn, Mo, Ni, Pb, Se and Zn） of the samples from Jiaozhou Bay and the previous reported Rushan Bay were performed. It has been found that the samples from the two bays are ap- proximately classified into two kinds using hierarchical cluster analysis, and a four-factor model based on principle component analysis could explain approximately 75% of the detection data, also linear discriminant analysis can be used to develop a prediction model to distinguish the samples from Jiaozhou Bay and Rushan Bay with accuracy of about 93%. The results of the present investi- gation suggested that the inorganic elemental fingerprint based on the combination of the measured elemental content and chemom- etric analysis is a promising approach for verifying the geographical origin ofMeretricis concha, and this strategy should be valuable for the authenticity discrimination of some marine TCM.

Quantitative similarity assessment of non-linear chemical fingerprint of traditional Chinese medicine by similarity system theory

The similarities of the non-linear chemical （NLC） fingerprints of Radix Glycyrrhizaes from four producing areas and eight other traditional Chinese medicines （TCMs） were calculated, using a systemic similarity calculation method proposed and three other main calculation ones （Euclidean distance, correlation coefficient and included angle cosine）. All of the correlation coefficient similarities of different TCMs are higher than 0.952, and the included angle cosines are all higher than 0.962. So, both the conelation coefficient and included angle cosine similarities are unable to be used as the criteria for quantitatively evaluating the similarities of NLC fingerprints of TCMs. Although all of the Euclidean distance similarities of Berry Liquorices from four producing areas are less than 73, those of the other eight TCMs are all more than 180. The Euclidean distance cannot reflect the relative magnitudes of the feature differences in the NLC fingerprints very correctly. The systemic similarity method is the best among the four ones. All of the systemic similarities of Berry Liquorices from the four producing areas are higher than 0.962, while those of the other eight TCMs are all lower than 0.805, and the systemic similarity can reflect the differences between samples most faithfully, and can be used as a quantitative one evaluating the similarities of NLC fingerprints of TCMs, by which TCM could be distinguished and evaluated quickly, simply and exactly.

An ultra-robust fingerprinting method for quality assessment of traditional Chinese medicine using multiple reaction monitoring mass spectrometry

Chromatographic fingerprinting has been perceived as an essential tool for assessing quality and chemical equivalence of traditional Chinese medicine.However,this pattern-oriented approach still has some weak points in terms of chemical coverage and robustness.In this work,we proposed a multiple reaction monitoring(MRM)-based fingerprinting method in which approximately 100 constituents were simultaneously detected for quality assessment.The derivative MRM approach was employed to rapidly design MRM transitions independent of chemical standards,based on which the large-scale fingerprinting method was efficiently established.This approach was exemplified on QiShenYiQi Pill(QSYQ),a traditional Chinese medicine-derived drug product,and its robustness was systematically evaluated by four indices:clustering analysis by principal component analysis,similarity analysis by the congruence coefficient,the number of separated peaks,and the peak area proportion of separated peaks.Compared with conventional ultraviolet-based fingerprints,the MRM fingerprints provided not only better discriminatory capacity for the tested normal/abnormal QSYQ samples,but also higher robustness under different chromatographic conditions(i.e.,flow rate,apparent pH,column temperature,and column).The result also showed for such large-scale fingerprints including a large number of peaks,the angle cosine measure after min-max normalization was more suitable for setting a decision criterion than the unnormalized algorithm.This proof-of-concept application gives evidence that combining MRM technique with proper similarity analysis metrices can provide a highly sensitive,robust and comprehensive analytical approach for quality assessment of traditional Chinese medicine.

Study on Elemental Fingerprint of Traditional Marine Chinese Medicine Oysters from Jiaozhou Bay,China

In order to investigate the relationship between the trace elements and the characteristics of the oysters, we analyzed the trace elements present in the germplasm of oysters from different producing areas in the Jiaozhou Bay. The element fingerprints were established to reflect the elemental characteristics of the oysters. Concentration patterns of the elements were deciphered by principle component analysis (PCA) and hierarchical cluster analysis (HCA). The six regions were discriminated with accuracy using HCA and PCA based on the concentration of 16 trace elements. The elements were viewed as characteristic elements of the oysters and the fingerprints of these elements could be used to distinguish the quality of the oysters.

Research of Quality Standards for Stachydrine Hydrochloride in Chinese Medicine TJF Granule

A high-performance liquid chromatographic method was applied to the determination of stachydrine hydrochloride concentration in TJF granule (Chinese name: Tiao-Jing-Fang), using a mobile phase of methanol-acetonitrile (50:50, v/v) by the Agilent Kromasi NH2 column (250 mm × 4.6 mm, 5 μm, S/N: 22N25110). Detection wavelength was 201 nm. The result revealed good linearity of stachydrine hydrochloride and was obtained within the range of 0.20 - 1.98 μg/mL (R = 0.9995). The average recovery was 97.01%;the relative standard deviation (RSD) was 0.19%. To the best of our knowledge, this is the first report dedicated to the determination of stachydrine hydrochloride by the evaporative light scattering detector-high-performance liquid chromatographic (ELSD-HPLC) method.

Integrated evaluation of HPLC fingerprints for the quality control of Ginseng Yang Rong Wan by multi-wavelength fusion fingerprint method

The aim of this study was to develop comprehensive evaluation methods for the quality control of Ginseng Yang Rong Wan(RSYRW).Multi-wavelength fusion fingerprints were successfully developed by high-performance liquid chromatography,which avoided the one-sidedness of single fingerprinting.Characteristic fingerprints of thirty batches of samples were generated at five wavelengths and evaluated by quantified ratio fingerprint method(QRFM).The results showed that thirty batches of samples were classified into seven grades.The methods established in this paper were found suitable for the analysis of Ginseng Yang Rong Wan.

Brain organoids are new tool for drug screening of neurological diseases

At the level of in vitro drug screening,the development of a phenotypic analysis system with highcontent screening at the core provides a strong platform to support high-throughput drug screening.There are few systematic reports on brain organoids,as a new three-dimensional in vitro model,in terms of model stability,key phenotypic fingerprint,and drug screening schemes,and particula rly rega rding the development of screening strategies for massive numbers of traditional Chinese medicine monomers.This paper reviews the development of brain organoids and the advantages of brain organoids over induced neurons or cells in simulated diseases.The paper also highlights the prospects from model stability,induction criteria of brain organoids,and the screening schemes of brain organoids based on the characteristics of brain organoids and the application and development of a high-content screening system.

中药材的不同产地鉴别技术研究概况

目的探讨中药材不同产地鉴别技术的研究现状和发展趋势,为中药材产地研究拓展思路。方法以“中药”“产地”“鉴别”等为关键字,在中国知网、维普网、PubMed、Web of Science等数据库中查询近10年发表的相关研究论文,并以“不同产地”和“鉴别技术”为主旨进行文献综述。结果中药材的不同产地鉴别技术包括性状与显微鉴别、理化鉴别、指纹图谱技术、DNA分子标记鉴别、生物效价评价和结合计算机算法的人工智能鉴别技术等多种方法,其中经验鉴别、显微鉴别和一般理化鉴别等传统鉴别方法简便易行,但依赖经验、专属性差;光谱法、指纹图谱、DNA标记技术等方法用于中药材产地鉴别克服了以上缺点,准确可靠、操作简便;结合计算机算法的人工智能鉴别技术更加准确高效,极大地降低了人工和时间成本,将成为未来发展的重要方向。结论中药材的不同产地鉴别存在一定的难度和不确定性,可以结合多种方法进行综合鉴别,发挥每种鉴别方法的优势,以确保结果的准确性。未来,中药材鉴别将更加智能化和自动化,利用人工智能、机器学习等技术可以提高鉴别效率和准确性。

Chemometrics and modernization of traditional Chinese medicine

Development of chromatographic fingerprinting and its related chemometric methods in the research of quality control of traditional Chinese medicines(TCMs) are discussed. The quality control methods for guarantying the authentication and stability of products and semi-products of TCMs are firstly assessed. The technique based on chromatographic fingerprinting is essentially a kind of high-through put and integral tools to explore the complexity of herbal medicines. In order to further control the comprehensive quality of TCMs,confirmation and identification of their important chemical components are necessary. Some new strategies are proposed to trace the chemical changes of chromatographic fingerprints both in product processing and/or after their administration by modern chromatographic techniques and chemometrics. Combined with systems biology and bioinformatics,it seems possible for one to reveal the working mechanism of TCMs and to further control their intrinsic quality comprehensively.

Determining method and conditional factors of electrochemical fingerprint of Chinese traditional medicine

The thermodynamic systems and kinetic model suitable for the electrochemical token of the compo-nent throng in Chinese traditional medicines have been analyzed. It has been indicated that the damp oscillatory reactions in the non-equilibrium close system and open system without the supplement of dissipative substance have important significance for the throng token and analysis of chemical com-ponents in Chinese traditional medicines. Various factors influencing the electrochemical fingerprint,such as reactant species and their concentrations,electrode types,temperature,stir rate,the kind,dosage and granularity of Chinese traditional medicines,have amply been researched by the B-Z os-cillatory reaction which used malonic acid as a main dissipative substance. In addition,the quantitative information about the chemical components in Chinese traditional medicines has been discussed in detail. The method and its conditions for determining the electrochemical fingerprint used in scientifi-cally distinguishing and evaluating Chinese traditional medicines have successfully been put forward.

Principle, traits and functions of electrochemical fingerprint of Chinese traditional medicine

In regard to such challenging analysis problems as scientific identification and quality evaluation of Chinese traditional medicine, the electrochemical fingerprint technique of Chinese traditional medi- cine has been researched. The principle, traits, functions, etc., of the electrochemical fingerprint have detailedly been analyzed and discussed by the B-Z oscillatory system using malonic acid as main dissipation substance, characterized by the fact that different influences of different Chinese traditional medicines on the mechanism of the oscillatory reaction cause different changes of the shape of the potential-time curve of the oscillatory system under the conditions of constant tem- perature and pressure. An economical, simple and convenient, easy pushing and effective scientific method for distinguishing and evaluating multifarious Chinese traditional medicines has success- fully been put forward.

中药谱效关系在中药中应用进展

中药谱效关系是利用数据分析技术将有效物质群特征峰与中药药效信息关联,反映中药物质成分与功效强度间复杂关系的一种方法。自中药谱效关系被提出后,由于其在中药活性成分群整体特征精细表达与中药多指标、多靶点作用机制联系上表现出的显著优势,现已被广泛应用于中药的质量控制、药效物质基础、炮制前后药效研究及有效部位筛选等研究领域。本文通过整理近十年中药谱效关系研究的相关文献资料,在中药谱效关系研究不断拓展、完善的新形势下,对中药谱效关系的研究策略及在中药多领域中的研究现状进行梳理与提炼,同时针对当前中药谱效关系研究存在的核心问题,进行初步分析展望,以期为谱效关系在中药多领域的深入研究提供参考。

近十年中药指纹图谱领域的研究现状及趋势分析

本文借助文献计量学的原理和方法总结中药指纹图谱领域的研究现状和趋势,为该领域的未来研究提供参考。本文收集中国知网、Web of Science核心数据库中的相关文献,并利用Microsoft Office Excel 2017、CiteSpace 6.3R1、VOSviewer1.6.20等进行中药指纹图谱领域的刊文趋势、作者机构合作、主题词共现、聚类、突现等分析。本文共纳入2 404篇文献,且本领域的相关研究在中医药权威性杂志中备受推崇。刊文趋势显示近十年来本领域研究大致可分为两个时期;主题词共现表明中药成分测定以及质量评价等一直是本领域的研究重点;突现分析提示指纹图谱领域的研究重心已转移至药对和经典名方上。结论表明,本研究系统分析整理了中药指纹图谱领域研究的发展变化及趋势演进,直观展示了本领域的研究热点和研究重点等信息,可为该领域的深入研究提供一定的参考。

不同来源产地酸枣仁药材的HPLC-DAD指纹图谱研究

目的:建立不同来源产地酸枣仁药材的高效液相色谱-二极管阵列检测法(HPLC-DAD)指纹图谱检测方法。方法:采用超声离心法提取12批不同来源产地酸枣仁药材中的化合物成分,通过梯度洗脱程序,检测204 nm波长下HPLC-DAD指纹图谱,并进行指纹图谱分析与评价。结果:通过指纹图谱的构建和分析,共计确认27个共有峰,指认5个活性化合物,指纹图谱中的相对保留时间接近,相似度较高。结论:本文建立的酸枣仁药材HPLC-DAD指纹图谱检测方法,处理简易,检测快速,操作便捷,可对未知样品进行鉴定、分类和评价。

New Progress in Modern Research on Chinese Herbal Medicines Published in Chinese Traditional and Herbal Drugs in 2010:Annual Highlights and Comments

As a series of and continuous publication,the papers published on Chinese Traditional and Herbal Drugs in 2010 were selectively and briefly highlighted to reflect the new progress on modern research of Chinese herbal medicines.Within 617 articles,chemical constituents(127),pharmaceutics and technology(149),pharmacological studies and clinical observation,and medicinal materials are still major categories.Some comments have also been personally provided.

High-Performance Liquid Chromatography Fingerprint of Marine Traditional Chinese Medicine Haliotidis

Objective: Haliotidis, the dried muscle of abalone, has long been used as a marine traditional Chinese medicine(TCM) due to its high medicinal and nutritive values, whereas few reports contributed to its quality control. This study aimed to establish the high-performance liquid chromatography(HPLC) fingerprints of Haliotidis. Materials and Methods: The HPLC fingerprints of Haliotidis, the manufacturing products of dried muscle of abalone, were analyzed by reverse-phase HPLC, using a YMC HPLC C18 column(250 mm × 4.6 mm, 5 μm).The gradient elution mode was applied with mobile phase starting from 5% acetonitrile and 0.1% phosphoric acid aqueous solution to 100%acetonitrile in 70 min at a flow rate of 1.0 mL/min. The detection wavelength was set at 190 nm. Results: Through compared the HPLC fingerprint chromatograms of 14 batches of Haliotidis, 25 peaks were assigned as the characteristic common peaks, of which one index component L-phenylalanine was identified by comparison with its standard substance. The established HPLC fingerprint analysis method of Haliotidis was validated with good precision, repeatability, and stability. Based on the above study, a reference HPLC fingerprint chromatogram of Haliotidis was proposed. Conclusions: It is the first time to establish the HPLC fingerprint chromatogram of TCM Haliotidis, which could contribute to the establishment of its quality control system.

中药色谱指纹图谱潜信息特征判据研究

目的对中药色谱指纹图谱潜信息特征进行判据研究,用F和I等37个指标揭示色谱指纹图谱的潜信息特征。方法用银杏叶提取物(GBE)、银杏达莫注射液(GLED I)和苦碟子(ISH)与苦碟子注射液(ISH I)的HPLC指纹图谱进行比较研究。结果从积分信号强度、信号均化程度、分离度、指纹信息量等多方面综合评价出GBE指纹图谱好于GLED I,ISH指纹图谱好于ISH I,GBE与ISH指纹图谱基本相当。结论F和I等37个指标可客观、真实、全面地揭示中药指纹图谱的潜信息特征。

中药色谱指纹图谱相似度计算中保留时间校正方法的研究

从保留时间校正方法对线性推移、非线性推移和时间延迟的校正效果方面探讨了保留时间校正方法的适用范围。认为一点法校正仅能校正线性推移;两点法可以校正时间延迟和线性推移,并能部分校正非线性推移。多点法使用分段线性逼近的方法对非线性推移有良好的校正效果。