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.

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.

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 correlation 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.

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 of Meretricis concha,which is a commonly used marine traditional Chinese medicine(TCM) for the treatment of asthma and scald burns.For that,the inorganic elemental contents of Meretricis 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(Al,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 approximately 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 investigation suggested that the inorganic elemental fingerprint based on the combination of the measured elemental content and chemometric analysis is a promising approach for verifying the geographical origin of Meretricis concha,and this strategy should be valuable for the authenticity discrimination of some marine TCM.

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.

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.

Establish a Three-dimensional Fluorescent Fingerprint Database of Traditional Chinese Medicines

Objective:To set up a database of three-dimensional fluorescence spectra of traditional Chinese medicines,Screening of medicinal materials by three-dimensional fluorescence spectroscopy,Methods:The paper Summarizes the three-dimensional fluorescence fingerprints,screens medicinal materials on basis of verifying the three-dimensional fluorescence spectra of the reference crude herbs of the national standard Chinese medicines,and combines with visual basic6.0 and microsoft access 2003 technology system to construct a three-dimensional fluorescence fingerprint database of TCMs.Results:the identification and quality control of traditional Chinese medicines(TCMs)was accuately and swiftly achieved.Conclusion:The relevant analysis on the operating system of database and the three-dimensional fluorescence spectrum database of TCMs indicates that this operating system can provide convenient channels for the inspection,verification and quality control of TCMs.

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.

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.

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.

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.

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.

中医教材历史沿革与建设探讨

教材不仅是培养高素质人才的知识传递载体、开展教育活动的主要依据,也是高等院校开展教学任务的重要工具。按照时期划分教材的发展阶段,分析中医药高等教育第一至十一版统编教材的历史背景、内容特点,以此了解中医教材的历史沿革,并采用历史制度主义的理论视角,从中医教材建设的深层结构、路径依赖和动力机制三个方面分析其演变规律,为中医教材的深层次研究开辟了新思路、新视野。有利于提升教材质量的同时,对丰富中医药高等教育统编教材的理论和实证研究具有重要意义。

具有“药辅合一”双重特性的中药凝胶在糖尿病足溃疡中的研究进展

糖尿病足溃疡常导致难愈性慢性创面,传统的纱布等敷料难以满足当前临床治疗的需求。新型“药辅合一”中药凝胶具备了治疗和敷料的双重特性,具有抗炎、抗溃疡和伤口修复等药理活性,同时能够提供创面修复所需要的湿润环境,有较好的伤口包裹性及优秀的生物相容性和低毒性,从而更好地满足临床需求。本文就常见的“药辅合一”中药凝胶在创面愈合方面的研究进展进行综述,为糖尿病足溃疡的治疗及后续功能性敷料的开发研究提供基础。

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.

石榴皮菝葜复方搽剂指纹图谱的建立及3种成分的含量测定

目的建立石榴皮菝葜复方搽剂(SLPBQ)指纹图谱,结合化学模式识别方法进行分析,并对主要成分进行含量测定。方法采用Waters XBriage C18色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈(A)-水(B),梯度洗脱,流速1.0 mL·min^(-1),进样体积10μL,检测波长270 nm,柱温30℃。采用《中药指纹图谱相似度评价系统(2012版)》绘制10批次SLPBQ的HPLC指纹图谱,确认共有峰,并分析多批次复方搽剂相似度。利用SPSS22.0及SIMCA-P14.1数据分析软件进行化学模式识别分析。通过单味药材及阴性对照图谱结合对照品比对指认化学成分,并对部分主要成分进行定量分析。结果10批次样品筛选出22个共有峰,且相似度均大于0.974;聚类分析将10批样品分为两大类;主成分分析筛选出5个主成分,累计方差贡献率为98.79%。对3种成分进行定量检测,发现各成分在各自浓度范围内的与峰面积线性关系良好(r≥0.9999),加样回收率为95.87%~103.76%,RSD均≤2%。结论该方法可用于SLPBQ的质量控制,简便、重复性好、稳定性好、准确度高。

中药材及饮片质量控制和评价的关键技术评析

中药材及饮片作为中药产业链条的最前端,其质量评价策略对中药质量的提升具有引领作用。随着现代技术的应用与发展,我国已形成了较为完善的中药材及饮片质量控制体系。笔者结合近年来中药材及饮片质量评价技术的应用现状和产业需求,对质量研究关键技术进行了梳理,强调了过程控制技术在中药饮片规范化生产中必要性,同时探讨人工智能仿生技术所具有的客观化、直观化特点在中药材及饮片检验中应用的可能性,在未来实现中药产业化进程中或具有重要意义。当前,指纹图谱和色谱—质谱联用技术作为代表性的化学成分分析手段,分别在中药材及饮片化学成分整体表征和痕量成分控制方面日益应用广泛;在生物技术应用中,DNA分子鉴定技术突破了传统鉴别手段,从中药种质源头进行质量控制;生物效应技术紧密结合临床功效进行质量评价,弥补了现行质量控制方法与功效相关性不足的特点。每种关键技术均具有其独特的优势,对于中药材及饮片质量的全面控制具有相辅相成的作用。本文对中药材及饮片质量控制的关键技术进行了总结和分析,并提出了相关的建议,以期对保障中药材及饮片的质量稳定及推动中医药大健康产业的可持续发展产生积极的作用。

不同产地杜仲的化学振荡体系电化学指纹图谱研究

建立了一种基于H_(2)SO_(4)-Ce(SO_(4))_(2)-KBrO_(3)-丙二酸-酒石酸双有机底物振荡体系的电化学指纹图谱方法,用于中药杜仲的产地鉴别。考察了体系的重现性、特异性,确定了最佳组成和测试条件,提出了电化学指纹图谱相似度的计算方法,评价了不同产地杜仲的相似度。结果表明,此电化学指纹图谱可用于鉴别和评价中药杜仲的道地性。该方法具有特征性强、灵敏度高等优势,操作简单、分析成本低等优点,可用于中药杜仲的产地鉴别。

当归精准煮散饮片质量均一性分析

目的:研究考察当归的精准煮散饮片与其原饮片的质量均一性,为中药饮片的临床应用质量均一性提供参考。方法:对当归药材原饮片和精准煮散饮片的干膏率进行比较,应用HPLC-DAD结合中药指纹图谱法对不同粒度精准煮散饮片及原饮片的煎煮液进行质量均一性评估。结果:就出膏率而言,精准煮散饮片高于原饮片。指标成分阿魏酸由0.32 mg/g提高至0.38 mg/g,同时共有峰的峰面积有不同程度增大,均匀度显示相对标准偏差(RSD)由4.82%降低至2.63%。结论:当归的精准煮散饮片与原饮片在本质属性上没有区别,但前者对于当归的有效成分溶出量和质量均一性均有所提高。