Authenticity discrimination of Pulsatillae Radix based on dry-process REIMS fingerprinting combined with machine learning / 中国中药杂志

In this study, rapid evaporative ionization mass spectrometry(REIMS) fingerprints of 388 samples of roots of Pulsatilla chinensis(PC) and its common counterfeits, roots of P. cernua and roots of Anemone tomentosa were analyzed based on REIMS combined with machine learning. The samples were determined by REIMS through dry burning, and the REIMS data underwent cluster analysis, similarity analysis(SA), and principal component analysis(PCA). After dimensionality reduction by PCA, the data were analyzed by similarity analysis and self-organizating map(SOM), followed by modeling. The results indicated that the REIMS fingerprints of the samples showed the characteristics of variety differences and the SOM model could accurately distinguish PC, P. cernua, and A. tomentosa. REIMS combined with machine learning algorithm has a broad application prospect in the field of traditional Chinese medicine.

Analysis of the of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. by PBET digestion in vitro/Caco-2 cell model and their cumulative risk assessment / 药学学报

Inductively coupled plasma mass spectrometry (ICP-MS) was applied to determine the concentrations of lead (Pb), cadmium (Cd) and arsenic (As) in Lindera aggregata (Sims) Kosterm. The physiologically based extraction test (PBET) digestion in vitro/Caco-2 cell model was established to investigate the bioaccessible contents of Pb, Cd and As in decoction of Lindera aggregata (Sims) Kosterm. The target-organ toxicity dose modification of HI method (TTD) was used to evaluate the cumulative risk caused by the combined exposure of the total levels of Pb, Cd and As in Lindera aggregata (Sims) Kosterm. and the bioaccessible contents in the decoction. The results showed that the total contents of Pb, Cd and As in 4 batches of samples were in the range of 2.901-3.872, 1.299-1.800 and 0.062-0.216 mg·kg-1, respectively. After transportation by Cacco-2 cells, the bioaccessible contents of Pb, Cd, and As in the decoction were in the range of 0.045-0.080, 0.070-0.112 and 0.004-0.018 mg·kg-1. The results of risk assessment showed that calculated by the total amounts of heavy metals in the Lindera aggregata (Sims) Kosterm., for the end points of nervous system, the cumulative risks of co-exposure of heavy metals in 3 batches of samples were of concern. After decoction and transportation by Caco-2 cells, for the end points of cardiovascular system, blood, nervous system, kidney and testis, the TTD modification of HI values of all batches of samples were less than 1, and the health risks were acceptable. The study provided methodology basis for a more objective assessment of the health risks of heavy metals and harmful elements in traditional Chinese medicine and for a more scientific limit standard of heavy metals and harmful elements.

Development of an overall evaluation system for traditional Chinese medicine / 药学学报

This paper reviews modern science and technology with regard to traditional Chinese medicine (TCM) research methods, quality control, and discusses the establishment and improvement of the evaluation system for TCM, focusing on the following issues: 1) How to incorporate the efficacy of TCM in the overall evaluation of TCM quality; 2) how to quantify the efficacy and properties of TCM; 3) how to understand the correlation between the efficacy and properties of TCM and its application; 4) how to reflect the specificity of the effective components in the overall evaluation of TCM quality; and 5) how to reflect the quality value transfer of effective components in the whole process of production and metabolism in vivo to the overall evaluation of TCM quality. The overall quality evaluation of TCM needs to better reflect its clinically safety and effectiveness. It is suggested to establish a clinical quality assessment method based on the content of the chemical components of TCM to explore and establish an overall evaluation method of TCM quality that reflects the efficacy of TCM and conforms with clinical practice.

Preliminary Considerations on Management Mode and Technical Evaluation of Traditional Chinese Medicine with Same Name and Prescription / 中国实验方剂学杂志

With the publication of Registration and Classification of Traditional Chinese Medicine （TCM） and Application Data Requirements， the related management and technical documents of TCM with the same name and prescription need to be further studied and formulated. In this paper， the management mode and technical evaluation of TCM with the same name and prescription are discussed to provide reference for the formulation of management and technical documents of TCM with the same name and prescription. The issues to be discussed include which management mode to adopt， how to select the control drugs with the same name and prescription， whether the indication risk level should be divided， whether the indication should be limited to medium and low risk， and how to carry out the technical evaluation of similarity/consistency. From the perspective of technical document research and formulation， this paper mainly focuses on the technical level. However， there are still other theoretical possibilities in the management mode and technical evaluation of TCM with the same name and prescription. Therefore， this paper， as a preliminary summary of the management and technical evaluation of TCM with the same name and prescription， needs more scholars and industry experts to pay attention to and participate in this work.

Considerations on Relevant Technical Requirements for Listing Application of Over-the-counter Traditional Chinese Medicine / 中国实验方剂学杂志

In this paper， a comparative analysis is carried out on the policy of listed drugs in Australia， the policy of over-the-counter drugs in Japan， the policy related to the conversion of Chinese patent medicines to over-the-counter drugs， and the policy related to health food. The focus is on one of the possible situations for the registration of over-the-counter traditional Chinese medicines （TCMs）， namely new prescription-composed over-the-counter TCMs. This paper discussed separately from the three parts of the scope of Chinese medicinal materials in the prescription medicines， the scope of indications， and the technical requirements， in order to provide references for the technical requirements related to the registration of over-the-counter TCMs. Recommendations on the marketing and registration of new prescription-composed over-the-counter TCMs：①It is recommended to formulate a list of medicinal materials for the use of Chinese herbal medicines， and consider including raw materials of health food. On this basis， a batch of safe Chinese medicinal materials/decoction pieces was added. And consider dynamic supervision， such as allowing the addition or recall of Chinese medicinal materials/decoction pieces in the list of medicinal materials. ②The scope of indications is recommended to consider the scope of indications for the conversion of Chinese patent medicines to over-the-counter TCMs in China， and the selection of medium-risk indications can reflect the characteristics and advantages of TCM treatment. ③Efficacy evaluation needs to provide high-quality scientific evidence， including clinical research data， and consider relaxing the requirements for non-clinical pharmacodynamic trials.

Quantitation and content investigation of bilirubin in cultured cow-bezoar / 中国中药杂志

A determination method for bilirubin in cultured cow-bezoar was developed in this study, with which the bilirubin in 15 batches of samples was quantified. The samples were first processed with 10% oxalic acid solution for the conversion of bilirubin from conjugated to unconjugated, followed by the extraction with dichloromethane. Then the obtained sample solutions were analyzed at 450 nm by HPLC[chromatographic column: Agilent TC-C_(18)(4.6 mm × 250 mm, 5 μm); mobile phase: acetonitrile and 1% glacial acetic acid aqueous solution(95∶5); flow rate: 1.0 mL·min~(-1)]. The bilirubin content in the 15 batches of cultured cow-bezoar was ranged from 21.9% to 41.7% with the average of 32.4%. The proposed method is accurate and reliable, thus making it suitable for the quantitation of bilirubin in cultured cow-bezoar and its quality assessment and control.

Study on potential hepatotoxicity of main monomers of Polygonum multiflorum based on liver micro-tissue / 中国中药杂志

In this study, we aimed to establish a rat liver micro-tissue evaluation system to evaluate the hepatotoxicity of the main monomers in Polygonum multiflorum. Rat primary hepatocytes were isolated and purified by two-step in situ perfusion method to prepare hepatic parenchymal cells. The ultra-low adsorption plate and the inverted model were used to establish an in vitro hepatotoxicity evaluation system. After the system was established, the main monomer components(monanthone with emodin type, rhein, emodin, emodin-8-O-β-D-glucopyranoside, physcion) of P. multiflorum were selected for in vitro hepatotoxicity evaluation. This study showed that the primary cells of the liver can form liver micro-tissues in the low adsorption plate method and the mold perfusion method, with good liver structure and function, which can be used to evaluate the hepatotoxicity of the drug to be tested after long-term administration. The five monomers to be tested in P. multiflorum can significantly affect the proliferation of primary liver micro-tissues in rats in a dose-and time-dependent manner. The hepatotoxic effects were as follows: monanthone with emodin type > rhein > emodin > emodin-8-O-β-D-glucopyranoside > physcion. The results suggested that the emodin-type monoterpene and rhein might be the potential hepatotoxic components, while the metabolites of emodin-8-O-β-D-glucoside and emodin methyl ether showed more toxic risks. The rat primary hepatocyte micro-tissue model system established in this experiment could be used to achieve long-term drug administration in vitro, which was consistent with the clinical features of liver injury caused by long-term use of P. multiflorum. The experimental results provided important information and reference on the clinical application and toxic component of P. multiflorum.

Discussion on evaluation mode of proficiency testing for heavy metal and harmful element detection in medicines / 中国中药杂志

This study aims to explore the evaluation model for the proficiency testing of heavy metal and harmful element residues in pharmaceuticals,and to provide reference for the proficiency testing program and proficiency testing result in the field of residue analysis. The proficiency test result of cadmium determination in honeysuckle as an example. The algorithm A,NIQR,and Horwitz function are used to calculate the assigned value and the standard deviation. Z was obtained at the same time. If | Z | ≤2,the result is satisfactory. If 2< | Z | <3,the result is questionable. If | Z | ≥3,the result is unsatisfactory. In addition,the median value is the assigned value,and deviation(D%) is used. If D% is not more than 16%,the result is satisfactory; if D% is more than 16%,the result is unsatisfactory. After analysis,in the results of questionable or dissatisfied laboratories calculated by algorithm A and NIQR,the deviation error of some data is within the scope of the standard. In the results of the satisfactory laboratory evaluated by the Horwitz function,some data deviation errors far exceed the standard range. The evaluation result of the D% meets the requirements. According to heavy metal and harmful element trace analysis methods,this study is the first to apply D% to the evaluation of the detection ability of heavy metals and harmful elements in pharmaceuticals. This method makes the evaluation result more reasonable,and has important reference significance for the evaluation of other proficiency test results.

Comparative studies of three Cistanche speices based on UPLC specific chromatogram and determination of main components / 中国中药杂志

Based on UPLC specific chromatogram and determination of seven main components,this study aimed at evaluating the quality of Cistanche deserticola,C. tubulosa and C. sinensis. Echinacoside,cistanoside A,verbascoside,tubuloside A,isoacteoside,2'-acetylacteoside,tubuloside B were used as reference substances. UPLC analysis was performed on a Waters ACQUITY UPLC HSS T3 column( 2. 1 mm×100 mm,1. 8 μm). The mobile phase was acetonitrile-0. 08% trifluoroacetic acid solution. The flow rate was0. 3 mL·min-1,and the injection amount was 10 μL. The column temperature was 40 ℃,and the detection wavelength was 330 nm.The UPLC specific chromatograms were processed with ChemPattern software. UPLC specific chromatograms of C. deserticola and C.tubulosa from different samples were of high similarity,but the similarities of their counterfeit C. sinensis were less than 0. 06. Both of cluster and principal component analysis can distinguish certified products and counterfeits. The content ratios of echinacoside/verbascoside and verbascoside/isoacteoside were quite different between C. deserticola and C. tubulosa,which had distinct significance.The UPLC specific chromatogram and contents of seven main components can provide a basis for quality evaluation of Cistanches Herba.

Research progress on chemical constituents and quality control of Tripterygium wilfordii preparations / 中国中药杂志

Tripterygium wilfordii preparations,with various biological activities such as immunosuppressive,anti-inflammatory and anti-cancer effects,are widely used in the treatment of autoimmune diseases such as rheumatoid arthritis,lupus erythematosus,and nephrotic syndrome. They have definite therapeutic effect,but often cause serious adverse reactions and result in damages to liver,kidney,blood,reproduction,and other systems due to their complex compositions,great toxicity,and narrow margin between the toxic and therapeutic dosages. At present,T. wilfordii preparations produced by different manufacturers exhibit large variations in clinical efficacy and side effects in account of their different chemical compositions and quality fluctuation due to differences in raw materials and production process. However,the existing quality standards are controversial in terms of index components and content limit,which cannot be effectively used for the overall quality control of the preparations. In this paper,the research progress on chemical constituents,quality standard and quality control methods of four T. wilfordii preparations including Tripterygium Tablets,Tripterygium Zongtie Tablets,Tripterygium Shuangceng Tablets and Tripterygium Glycosides Tablets was reviewed,in order to provide ideas and reference for the quality improvement of this type of preparations.

Screening of multiple pesticide residues in Jinyinhua Formula Granules / 中国中药杂志

To evaluate the pesticide residue risk of Jinyinhua Formula Granules( made from Lonicerae Japonicae Flos) used in the market preliminarily,20 samples of Jinyinhua Formula Granules from 5 manufactures were collected randomly through the national evaluative sampling test program. Totally 262 pesticides( involving 270 chemical monomers) with monitoring significance to traditional Chinese medicinal materials were detected. Samples were extracted by high speed homogenate with acetonitrile as solvent. And their residues were analyzed by GC-MS/MS and LC-MS/MS in MRM mode. No less than 2 groups of characteristic ion pairs were adopted for qualitative detection,and the calibration curve method was used for quantitative detection. The results showed that 20 pesticides were detected in 20 batches of Jinyinhua Formula Granules,with an average of about 9 pesticides detected in every batch,but no restricted pesticide was detected. The detected pesticides were all at the trace level,which was far lower than the limit of the general food standard. Therefore,the safety risk was low in Jinyinhua Formula Granules. In this study,a screening method for pesticide residues in Jinyinhua Formula Granules was established for the first time. The method was accurate and rapid,and the detection indicators were highly targeted. The results could provide theoretical reference for the prevention and control of pesticide safety risks in Jinyinhua Formula Granules and even traditional Chinese medicine formula granules.

Determination and risk assessment of heavy metals and harmful elements residues in Niuhuang Qingwei Pills based on ICP-MS / 中国中药杂志

To achieve a comprehensive understanding of heavy metals and harmful elements residues in Niuhuang Qingwei Pills,49 samples from 18 manufactures were collected from 31 provinces in China.Risk assessment and control preparations were applied innovatively in evaluation of exogenous pollution in traditional Chinese Medicine.Determination methods for Pb,Cd,As,Hg and Cu were established by inductively coupled plasma mass spectrometry(ICP-MS).Based on the procedures including hazard identification,hazard characterization,exposure assessment and risk characterization,risk assessment was performed and residual limits for Pb,Cd,As,Hg and Cu in the drug were formulated.The results showed that the hazardous quotients(HQ) of the elements were decreased in the following order:Pb>As>Cu>Hg>Cd,and the total hazardous index(HI) of heavy metals and harmful elements in Niuhuang Qingwei Pills was above 1,implying health risk of the drug.Under the proposed limits,5 elements in the control preparation as well as Cd and Cu in the samples were within the limits range,but the excess rates of Pb,As and Hg in the samples were 12%,12% and 14%,respectively.For the first time,basic steps for risk assessment of Chinese patent medicine were established,which provided model and reference for risk assessment and limit formulation of other drugs.

Risk assessment of pesticide residues in domestic ginsengs / 中国中药杂志

The study aims at taking risk assessment of pesticide residues in ginseng and high risk pesticides were picked up in order to provide a scientific basis for the establishment of maximum residue limits(MRLs) for pesticides in ginseng. Residues of 246 pesticides in 80 ginseng samples collected from different place were detected by GC-MS/MS and LC-MS/MS method. Acute and chronic intake risks were evaluated by using deterministic approach, and the matrix ranking developed by the Veterinary Residues Committee of the United Kingdom was referred to assess risk score of pesticides. The 25 kinds of pesticide residues were detected in ginseng samples, the detection rate of quintozene(PCNB) was 78%, which was the most frequently detectable pesticide. The chronic dietary intake risks of 25 pesticide residues expressed as %ADI were 0.00%-2.6%, and their acute dietary intake risks expressed as %ARfD were 0.00%-104.2%. Among them the acute dietary intake risks of PCNB was 104%,which was the highest. The 25 pesticides were divided into 3 groups by risk score, high risk group(4 pesticides), medium risk group(6 pesticides), and low risk group(15 pesticides). Hexachlorobenzene, phorate, PCNB and BHC were classified as high risk group. It is necessary and effective to establish the limit of residual organic chlorine in ginseng from Chinese Pharmacopoeia(2015 edition). MRLs for PCNB and hexachlorobenzene in ginseng were proposed to be revised based on the results of risk assessment.

Discussion on source, preparation and quality of Indigo Naturalis / 中国中药杂志

For the discussion of the source, preparation and quality problems of Indigo Naturalis, the historical tradition and reality were summarized by literature survey and producing area investigation. Besides some quality problems, potential safety hazards were found out in some samples from market tested. Because lime could not be dislodged enough from Indigo Naturalis in the process of purification, the samples of Indigo Naturalis contained too much lime and showed strong alkalinity. It was suggested that the quality standard of Indigo Naturalis should be revised and revised and some detection projects and methods should be added into the standard. In addition, we suggested that the production access of Indigo Naturalis should be further defined.

Construction and application of effect-related near-infrared spectroscopy for traditional Chinese medicines — Exemplification by rhubarb dispensing granules / 药学学报

Consistency in quality of traditional Chinese medicine granules is an important factor to ensure reproducible clinical efficacy. In this study rhubarb dispensing granules were utilized to construct an efficacious near-infrared spectroscopy (eNIRS) assay by combining NIRS and biopotency. A NIR method for assaying rhubarb dispensing particles was established, and information on different batches was collected. The diarrhea-inducing biopotency of rhubarb dispensing granules was determined based on a constipation model induced by diphenoxylate in mice. The animal protocol was approved by the Animal Ethic Committee​ of 302 Hospital of Chinese PLA People's Liberation Army (ID: IACUC-2019-0010). Ten anthraquinones were determined in rhubarb dispensing granules by UPLC. The correlation between NIR and biopotency was analyzed and five characteristic bands that correlated highly with bioactivity were identified, including 4 011-4 390, 4 859-5 461, 7 012-7 493, 10 992-11 312 and 11 871-12 489 cm-1. There were some differences in the main bands of different chemical constituents. In summary, five active bands based on NIRS were identified and found to be able to achieve rapid on-line detection of rhubarb dispensing granule quality. This research model may also provide reference for quality control of other Chinese medicine dispensing granules.

Market quality surveillance and analysis of chinese medicinal materials and decoction pieces in 2017 / 中国中药杂志

With the rapid development of traditional Chinese medicine (TCM) in China as well as the implementation of the four most strict requirements, the quality of Chinese medicinal materials and decoction pieces had beem improved in recent years, however new problems and challenges were occurred. All the data of Chinese medicinal materials and decoction piece in special inspection,supervision test and evaluation inspection of drug administration department to were summarized and analyzed evaluate and analyze of the quality of Chinese medicinal materials and decoction pieces in 2017. On this basis, the relevant quality control strategies and suggestions were put forward for the relevant departments of China Food and Drug Administration to formulate and implement regulatory measures, furthermore to improve drug standards, and ensure the safety of medication.

Study on ethnic medicine quantitative reference herb,Tibetan medicine fruits of Capsicum frutescens as a case / 中国中药杂志

High price and difficult to get of reference substance have become obstacles to HPLC assay of ethnic medicine. A new method based on quantitative reference herb (QRH) was proposed. Specific chromatograms in fruits of Capsicum frutescens were employed to determine peak positions, and HPLC quantitative reference herb was prepared from fruits of C. frutescens. The content of capsaicin and dihydrocapsaicin in the quantitative control herb was determined by HPLC. Eleven batches of fruits of C. frutescens were analyzed with quantitative reference herb and reference substance respectively. The results showed no difference. The present method is feasible for quality control of ethnic medicines and quantitative reference herb is suitable to replace reference substances in assay.

Discussion on application of principal component analysis in analysis of traditional Chinese medicines and natural drugs / 中国中药杂志

Principal component analysis is a widely used chemometric method. In this paper, the development history of principal component analysis was summarized, and then its basic principle was elaborated. Afterwards, its applications in the analysis of traditional Chinese medicines and natural drugs were classified and discussed with some representative examples. Finally, the prospect of its application was outlooked at the end of this paper.

Content determination of four diester diterpenoid alkaloids in leaves of Aconitum kusnezoffii by HPLC / 中国中药杂志

This present study is to develop an HPLC method for simultaneous determination of four diester diterpenoid alkaloids, beiwutine, mesaconitine, hypaconitine and aconitine in the leaves of Aconitum kusnezoffii, so as to provide evidence of the quality control of this herb. The four constituents were measured on a Waters XBridge CC₁₈ column(4.6 mmχ250 mm, 5 μm). The mobile phase was acetonitrile-40 mmol·L⁻¹ ammonium acetate solution(adjusted pH to 10.5 with ammonia solution)(33:67) with isocratic elution at a flow rate of 1.0 mL·min⁻¹; the detection wavelength was 235 nm; the column temperature was 30 °C, and the injection volume was 10 μL. Next, this contents of the four diester diterpenoid alkaloids in 12 samples were 0.025 5-0.088 5, 0.039 1-0.071 5, 0.026 6-0.081 0 and 0.008 12-0.031 2 mg·g⁻¹, respectively. Next, this method has been successfully applied to the analysis of A. kusnezoffii folium in different harvest periods. The contents of the four alkaloids decreased primarily, and then increased with the postponing of harvest. The established method is proved to be accurate and sensitive for the determination of alkaloids in A. kusnezoffii folium, and may be useful for the quality improvement of this herbal medicine. Moreover, these results indicated the scientific significance for the toxicity and the suitable harvest time of this herb.

Study on original investigation, macroscopic and microscopic identification of pharmacopoeia contained species of Epmedii Folium / 中国中药杂志

Epimedii Folium is a commonly used traditional Chinese drug, and now still depends on the wild resource. In recent years, with the surge in consumption, the resources are declining, the use of market varieties are constantly changing. In this paper, Production and sales situation of the five species contained in pharmacopoeia(Epimedium brevicornu, E. sagittatum, E. pubescens, E. koreanum and E. wushanense) have been studied on the basis of the existing researches, in-depth investigation and collection of accurate plant specimens and samples. And the origins of Epimedii Folium regulated by the pharmacopoeia have been discussed. At the same time, more exclusive and practical features have been summarized on the basis of observation and comparison with the stereo, optical and stereo-fluorescence microscopy technologies, and refering the related literatures on leaf structure and anatomy.The results of this study will provide a useful reference for the clinical medication, supervision, inspection, and standard drafting and so on.