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Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.
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Heavy metals and other harmful elements in traditional Chinese medicines inflict serious damage on public health. Therefore, risk assessment of Chinese raw materials has gained increasing attention. To date, few reports have been published on the health risk assessment of heavy metals and harmful elements in Chinese patent medicines. To gain a comprehensive understanding of heavy metals and other harmful elements in Chinese patent medicines and to establish proper limits, residual Pb, Cd, As, Hg, Cu and Cr in 15 054 samples of 295 drugs was analyzed with regard to distribution and variation between elements and dosage forms. In addition, in accord with procedures including hazard identification, hazard characterization, exposure assessment and risk characterization, basic procedures and specific parameters for risk assessment of heavy metals and harmful elements in Chinese patent medicines were clarified based on the health risk assessment of 14 787 samples and 276 drugs. A method and equation for establishing residual limits is proposed. The results show that content and target hazard quotients (THQs) of the investigated elements in all samples showed a skewed distribution approaching 0. Content of Pb, As, Cu, Hg, Cd or Cr in the samples exceeded 100 mg·kg-1 and the content of Pb, As, or Cu in individual samples exceeded 1 000 mg·kg-1. THQs of 586 samples and four drugs were above 1. We believe that the health risk of Hg, Pb and As in Chinese patent medicines with dosage forms of pill, capsule, tablet and powder, especially those in raw powder preparations, warrant concern.
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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.
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China , Drug Contamination , Drugs, Chinese Herbal , Reference Standards , Metals, Heavy , Risk AssessmentABSTRACT
OBJECTIVE： To conduct a comprehensive and systematic qualitative investigation on chemical components in Shengmai injection. METHODS： Gas chromatography-mass spectroscopy (GC-MS) with pre-column derivatization, rapid resolution liquid chromatography-ion trap-tandem mass spectroscopy (RRLC-IT-MSn) and ion exchange chromatography (IEC) with post-column derivatization were applied in identification of saccharides, saponins, lignins and amino acids in the sample. Furthermore, preliminary investigation on test of macromolecules was performed using size exclusion chromatography-evaporative light scattering detection (SEC-ELSD). RESULTS： Fructose, glucose, sucrose, maltose, 5-hydroxymethyl-2-furaldehyde, 19 saponins, 14 lignins and 16 amino acids were found in Shengmai injection. CONCLUSION： The proposed methods are simple and accurate. The main chemical substantial basis of Shengmai injection is clarified, laying a foundation for further assay of chemical components.
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OBJECTIVE: To discuss the quality status of TCM raw powder preparations based on TCM raw powder preparation special project of national post-market drug surveillance in 2018. METHODS: The statutory standards of seven TCM raw powder preparations, including Qingwei Huanglian pills, Jianpi pills, Qipi pills, Shangqing pills, Renshen Guipi pills, Yimu pills and Niuhuang Qingwei pills, were analyzed. The test methods for adulteration, dyeing, sulfur dioxide, pesticide residues, aflatoxins, heavy metals and harmful elements and irradiation were established to reveal the safety risk. Whole-ingredient identification methods were developed to evaluate the authenticity of the drug. RESULTS: The statutory standards of the TCM raw powder preparations tested in national post market surveillance in 2018 are simple and inadequate to comprehensively control the quality of the drugs. Unqualified feeding, adulteration, and contamination with Pb, As and Hg were the main problems currently. Dyeing, aflatoxins and pesticide residues were found in very few samples. Contamination risk of sulfur dioxide was low in TCM raw powder preparations. Most manufacturers adopted irradiation for sterilization. CONCLUSION: The standards of TCM raw powder preparations should be improved to realize whole-ingredient identification. And heavy metals and harmful elements should be investigated. The manufacturers should enhance quality control of the raw material and pay attention to the risk of adulteration and harmful residues. Special project of national post-market surveillance can reveal common problems of similar drugs, which is a powerful measure for drug regulation.
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With the growth of number of Chinese patent medicines and clinical use, the rational use of Chinese medicine is becoming more and more serious. Due to the complexity of Chinese medicine theory and the uncertainty of clinical application, the prescription review of Chinese patent medicine always relied on experience in their respective, leading to the uncontrolled of clinical rational use. According to the traditional Chinese medicine (TCM) theory and characteristics of the unique clinical therapeutics, based on the practice experience and expertise comments, our paper formed the expert consensus on the prescription review of Chinese traditional patent medicine for promoting the rational use of drugs in Beijing. The objective, methods and key points of prescription review of Chinese patent medicine, were included in this expert consensus, in order to regulate the behavior of prescription and promote rational drug use.
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Objective To identify whole ingredients in Niuhuang Qingwei Pills (NQP) and give primary grade evaluation of NQP. Methods Firstly, microscopic characteristics specified by the statutory standard of NQP were summarized. Then new microscopic identification methods were established for Sennae Folium and Gypsum Fibrosum while new thin layer chromatography (TLC) identification methods were established for Bovis Calculus Artifactus, Borneolum Syntheticum, and Rhei Radix et Rhizoma. In addition, microscopic identification method for Menthae Haplocalycis Herba was improved. In this way, whole-ingredient identification of 17 materials were realized. NQP reference drug was developed and applied as accompanying control in whole-ingredient identification and primary grade evaluation of the samples. Results According to the results of 48 samples from 18 manufactures by primary grade evaluation, 10, 37, and 1 samples were classified as superior, qualified, and unqualified, respectively. Conclusion The proposed methods are accurate, simple, and objective, which offers a more comprehensive approach for quality control of NQP. And the methods provide research strategy and experimental basis for further work on establishment of grade standard.
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Traditional Chinese medicine (TCM) reference drug is a new form of TCM standard reference substance. The purpose of this guideline is to guide the establishment of the reference drug and standardize its investigation and application in national drug standards. Definition of TCM reference drug was specified and relating guideline and technical requirement were introduced in this paper. Its application in quality control of TCM was analyzed and the developing train was proposed. There is a wide prospect for the application of reference drug in quality control of TCM. Thus it has practical significance to explore and conduct the quality evaluation system by using TCM reference drug as the reference substance.
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OBJECTIVE: To establish a rapid approach for quality evaluation of Huoxiang Zhengqi Tincture. METHODS: Fingerprint was established by ultra performance liquid chromatography (UPLC) method and method evaluation was performed. By comparing with reference substances, reference drugs and reference extractives, the characteristic peaks and their ascriptions were investigated. Twenty-eight batches of samples from 13 manufactures were determined and their fingerprints were compared. Then two dimensional hierarchical cluster analysis (2D-HCA) and principal analysis (PCA)were applied in pattern recognition. RESULTS: Eighteen characteristic peaks were mainly related to Magnoliae Officinalis Cortex, Citri Pericarpium Reticulatae, Angelicae Dahuricae Radix, Extractum Glycyrrhizae, Atractylodis Rhizoma and patchouli oil. The UPLC fingerprints of samples from different manufacturers differed a lot. The results of 2D-HCA and PCA were consistent, which indicated that the fingerprints of the samples from the same manufacturer could cluster to their own group and the characteristic peaks of honokiol, magnolol and hesperidin showed the greatest impact on the fingerprints. CONCLUSION: UPLC fingerprinting with aid of chemometric analysis is rapid, simple, objective and easy to realize digitalization, thus providing a novel way for quality evaluation of Huoxiang Zhengqi Tincture.
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OBJECTIVE: To investigate a rapid approach for quality evaluation of Huoxiang Zhengqi Tincture. METHODS: Hesperidin, glycyrrhizic acid, imperatorin, honokiol, isoimperatorin, magnolol and atractylodin in Huoxiang Zhengqi Tincture were determined by ultra performance liquid chromatography (UPLC) method combined with wavelength switching detection technology. The sample was injected directly without preprocessing. The separation was performed on an ACQUITY UPLC BEH C18 (2.1 mm×100 mm, 1.8 μm) and the column temperature was maitained at 40℃. The mobile phase was composed of acetonitrile and 0.1% phosphoric acid with gradient elution at a flaw rate of 0.3 mL·min-1. Hesperidin was detected at 284 nm; glycyrrhizic acid was detected at 250 nm; imperatorin, honokiol, isoimperatorin and magnolol were detected at 300 nm; atractylodin was detected at 340 nm. RESULTS: The calibration curves of the seven components showed good linearity within their test ranges. The average recoveries for hesperidin, glycyrrhizic acid, imperatorin, honokiol, isoimperatorin, magnolol and atractylodin were 99.3%, 99.5%, 101.5%, 99.3%, 100.6%, 99.0% and 99.6%, respectively. And there were great variations among the contents of glycyrrhizic acid, imperatorin, isoimperatorin and atractylodin in 28 batches of samples from 13 manufactures. CONCLUSION: The proposed method is accurate, simple and rapid, thus providing basis for comprehensive quality control of Huoxiang Zhengqi Tincture.
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Application of microscopic spectroscopy in quality control of Niuhuang Qingxin pills was discussed. First, microscopic characteristics specified by the statutory standard of Niuhuang Qingxin pills were summarized. Then new identification method was established for Dioscoreae Rhizoma, Saigae Tataricae Cornu, Cinnamomi Cortex and Saposhnikoviae Radix. Finally, microscopic spectroscopy was used for test of Dioscoreae Rhizoma's adulterant Dioscoreae Fordii Rhizoma.It was the first time for this technology being applied in adulteration test of Chinese patent medicine.The results showed that Saigae Tataricae Cornu was not detected in 2 batches of Niuhuang Qingxin pills from 1 manufacturer while Dioscoreae Fordii Rhizoma was detected in 3 batches of samples from 2 manufacturers. The proposed methods were accurate, simple, rapid, objective and economic, which offered a more comprehensive approach for quality control of Niuhuang Qingxin pills. It was indicated that conventional technology such as microscopic spectroscopy could play an important role in identification of traditional Chinese medicine whose index ingredient was deficient or tiny.
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OBJECTIVE: To discuss quality control of Chinese patent medicine with animal ingredients, providing reference for standards improvement, quality supervision and regulated production. METHODS: Statutory standards and exploratory studies of Chinese patent medicines with animal ingredients tested in national post market surveillance between 2010 and 2014 were summarized. And technologies and methods developed for specific drugs were analyzed from the perspectives of safety, authenticity, effectiveness and controllability. RESULTS: Use of HPLC and GC is becoming more mature. Traditional microscopic and TLC methods can play a positive role in identification of animal drugs without index component. Mass spectrometry has been successfully applied in quality control of Chinese patent medicine with animal ingredients. CONCLUSION: National post market surveillance can provide comprehensive and elaborate evaluation on drug quality and can reveal potential risks. It's a powerful measure to promote quality of animal medicine.
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Crystal structures of chemical drugs has been being investigated widely. But few attention has been paid to polymorphs-phenomena of active ingredients from Traditional Chinese Medicine(TCM). Taking anhydrous dehydroandrographolide and hydrousprim-O-glucosylcimifugin as example, differences between TCM reference substances (RSs) with different crystal structures were discussed by using microscopy, melting point determination, differential thermal analysis (DTA) and infrared (IR) methods. The results showed that different crystal structures could lead to change of melting points, thermal behaviors and IR spectrum. It's indicated that polymorphs may be considered if different physicochemical properties were obtained when applying TCM RS. Differences of chemical properties of active ingredients from TCM with different crystal structures need further investigation.
Subject(s)
Crystallization , Differential Thermal Analysis , Methods , Reference Standards , Drugs, Chinese Herbal , Chemistry , Reference Standards , Medicine, Chinese Traditional , Molecular Structure , Reference Standards , Spectrophotometry, Infrared , Methods , Reference Standards , Transition TemperatureABSTRACT
OBJECTIVE: To evaluate and analyze the quality status of Huoxuezhitong powders and Huoxuezhitong capsules, providing reference for standards improvement, quality supervision and regulated production of related drugs. METHODS: Samples were tested according to the statutory standards. And exploratory study were carried out concerning safety, effectiveness, homogeneity and stability, using TLC, HPLC, UPLC, GC, LC-MS, ICP-MS, NIR and other techniques. New methods were established and adopted to investigate the quality of the preparations and their raw materials. RESULTS: All the samples met the requirements of the current specifications while the exploratory study could reflect the quality of the drugs in a more comprehensive way. CONCLUSION: The results suggest that the quality standards for Huoxuezhitong powders/capsules need to be improved and unified, and the manufacturers should pay attention to the quality of raw materials like olibanum, Eupolyphaga Steleophaga, pyritum, and borneolum syntheticum.
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OBJECTIVE: To investigate the influence of extracting methods on the content of soluble arsenic in Chinese traditional patent medicine containing realgar. METHODS: Soluble arsenic in traditional Chinese medicines niuhuang xiaoyan tablets was determined by atomic fluorescence spectrometry. The impact of several factors on the determination result was discussed, such as extraction solvents, extraction methods, extraction time, compound extraction and purification method. Then methodological study on the optimized method was carried out. RESULTS: Samples from 14 different manufactures were extracted with simulated intestinal fluid for 24 h at 37°C and the contents of soluble arsenic were between 200 and 1353 mg · kg-1. CONCLUSION: The proposed method is simple, sensitive and accurate, and can provide reference for the quality assessment of TCM products containing realgar.
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OBJECTIVE: To improve the quality standards of Huoxue Zhitong Powders and Huoxue Zhitong Capsules. METHODS: Angelicae Sinensis Radix, Olibanum and Borneolum Syntheticum were identified simultaneously by TLC method. Ferulic acid was detected by HPLC method. RESULTS: Clear spots were obtained with good separation in TLC identification. For the HPLC determination of ferulic acid, the calibration curve was linear in the range of 0.2-200 μg · mL-1, the limit of detection was 0.054 μg · mL-1 and recoveries were between 95%-105%. CONCLUSION: The proposed method is specific, accurate, simple and applicable for better control of Huoxue Zhitong Preparations' quality.
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Methods for determination of heavy metals and harmful residues in traditional Chinese medicine injection were established. Graphite furnace atomic absorption spectrometry was used for determination of lead, cadmium and copper, atomic fluorescence spectrometry for arsenic and mercury. The preprocessing method was optimized. The average recoveries of 5 elements were between 91% and 112% while the precisions were less than 2%. The determination limit of lead, cadmium, copper, arsenic and mercury were 0.28, 0.014, 0.49, 0.19, 0.061 microg x L(-1), respectively. The proposed method was simple, sensitive, accurate and reliable, and could be used widely.