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??Pharmaceutical excipients are important ingredients of drugs, and the quality of it directly related to the safety of drug Compared to the 2010 edition, one of the most significant improvement of the 2015 edition of Chinese pharmacopoeia is the monographs of pharmaceutical excipients will be available in an individual book (Chinese Pharmacopoeia Book IV) And also, some new features will be found in the new edition??the doubled varieties of chronicled pharmaceutical excipients, the application of new techniques, the strict standards of the excipients for injection, the establishment of functionality??related characteristics This article will interpret the developing trend of the standards of pharmaceutical excipients and the effect of the trend on the entire pharmaceutical industry in the future via the improvement of Chinese Pharmacopoeia.     

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??Chinese Pharmacopoeia (Ch.P) 2015 edition is the 10th revision of Ch.P since the People??s Republic of China was established.The article is to describe the general situation about the development of Ch.P 2015 edition, it will play very important role for the Ch.P 2015 on improving the standards system, strengthening the quality control for the drug, increasing the application of the advance detection technology, enlarging the monographs adoption, Improving the general requirements and control for the drug safety as well as the leading the international drug standards.     

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??OBJECTIVE To evaluate the equivalence among three different methods for drug melting point determination:??method A1 by glass liquid thermometer, ??method A2 by digital display,and ?? method B by instrumental method. METHODS Five chemical reference substances with different melting points were selected as the target drugs, and different brands of melting point apparatus were used to determine melting point. The apparatus used by method A consists of a glass container for a liquid bath and fitted with a suitable means of heating.The obtained results of the melting point by method A1, A2 and B were evaluated by equivalence testing referring to the data of Proficiency Testing Scheme for the melting point determination of chemical drugs organized by NIFDC in 2015 and 2016. RESULTS Method A1, A2 and B were equivalent,and no significant difference were observed for the melting point values determined by the three methods. CONCLUSION There is no significant difference between the melting point determination method A and method B in the Chinese Pharmacopoeia(Ch.P), and the obtained melting point values are equivalent either by glass liquid thermometer or digital display while using method A. This experiment provides scientific data support for potential adoption of digital display in melting point apparatus by Ch.P.     

首批肝素相对分子质量国家对照品的建立

目的《中国药典》2015年版二部肝素钠、肝素钙新增相对分子质量与相对分子质量检查项,需建立首批肝素相对分子质量国家对照品及系统适用性对照品。方法以《美国药典》肝素相对分子质量测定用对照品(USP heparin sodium molecular weight calibrant,批号:F0L483)为肝素相对分子质量对照品,以《美国药典》肝素相对分子质量系统适用性对照品(USP heparin sodium identification,批号:G1L413)为肝素相对分子质量系统适用性对照品,采用《中国药典》2015年版二部肝素钠“相对分子质量与相对分子质量分布”检查法,对肝素相对分子质量国家对照品待标品(批号:140819-201501)及肝素国家对照品待标品(批号:140818-201501)进行相对分子质量与相对分子质量分布测定,由全国12个药检所及肝素生产厂家实验室协作标定。结果对肝素相对分子质量国家对照品待标品(批号:140819-201501)相对分子质量5000~42000的20个点的百分面积进行标定,对实验室内误差进行考察,12个实验室中有2个实验室(2号、7号)部分点的标准差(standard deviation,SD)为1%~2%,其余10个实验室的SD值均小于1%,对实验室间误差进行考察,20个数据点的SD值均小于1%。相对标准偏差(relative standard deviation,RSD)均小于10%。肝素国家对照品待标品重均相对分子质量实验室内SD值除2号实验室外,其余实验室SD小于180,实验室间SD为180,实验室间RSD为1.1%。结论经国家药品标准物质委员会审定后批准,肝素相对分子质量国家对照品待标品(批号:140819-201501),附带宽分布标样表,及肝素国家对照品待标品(批号:140818-201501),重均相对分子质量16200,可以用于《中国药典》2015年版二部肝素钠、肝素钙相对分子质量与相对分子质量分布检查使用。     

中药常规检查的历史发展和应用意义

中药常规检查是中药的各项工作之首,在中药鉴定中占据着重要的地位。常规检查结果是否达到国家标准,直接影响到中药研究结论正误和临床药效发挥好坏。1953年以来,《中华人民共和国药典》更替11次,常规检查的方法和标准趋于完善,涵盖的品类也越来越多元化。依据《中华人民共和国药典》,常规检查共分4大项目分别是杂质检查、水分检查、灰分检查和浸出物检查。现将对常规检查的4大项目分别进行探究,以出版《中华人民共和国药典》为主线,梳理其历史发展;以2020版《中华人民共和国药典》为准则,明确常规检查中4大项目内容,阐述其应用意义。同时,通过与其他国家的药典（《欧洲药典》《美国药典》《日本药典》）比较,找寻我国检测方法的优劣,针对性地提出完善意见,优化常规检查内容并展望其路线的发展方向。以期促进常规检查的科学发展,提高相关科研人员对常规检查的重视度。     

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??OBJECTIVE To establish the quality control system for the recombinant human GLP-1 analogue fusion protein.METHODS The potency of the fusion protein was determined by luciferase reporter gene assay. The purity was analyzed by non-reduced SDS-PAGE and SEC-HPLC respectively. RP-HPLC was used for the peptide mapping. ELISA was used to analyze the identification of the final products. The molecular mass and peptide mass spectra were analyzed by LC-ESI-MS technique. Other control tests were performed according to the requirements in the Chinese Pharmacopoeia (Volume ??, 2010 edition). RESULTS Control tests were performed on three different lots of bulks and final products of recombinant GLP-1 analog fusion protein by the developed methods. The results showed that all the indexes met the requirements in the Guideline for Quality Control of Recombinant DNA Products for Human Use and Chinese Pharmacopoeia (Volume ??, 2010 edition). The molecular weight of the recombinant human GLP-1 analogue fusion protein was 71 361.0, which was in conformity with the theoretical value. CONCLUSION The developed methods and standard may assure the safety, effectiveness, and controllability of the recombinant human GLP-1 analogue fusion protein, which might be used for the routine quality control of products of the same kind.     

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??OBJECTIVE To guide the establishment of limits of aflatoxins in traditional Chinese medicines and their preparations by a preliminary risk assessment. METHODS According to the ??Chinese Pharmacopoeia?? aflatoxin determination method,aflatoxins in traditional Chinese medicines and some preparations were determined, and quality control procedures were carried out.In accordance with the basic steps of risk assessment,a preliminary risk assessment was done for traditional Chinese medicines and some preparations.RESULTS According to the results of preliminary risk assessment of aflatoxins in Chinese crude medicines and preparations,the limits of aflatoxins in the Chinese Pharmacopoeia were recommended.CONCLUSION Aflatoxins are not a universal contaminationin traditional Chinese medicines and their preparations, but for some species which are at high risks, the detection of aflatoxins is needed and appropriate limits should be established.     

从质量标准复核和审评视角浅析中药配方颗粒标准制定工作(I)

中药配方颗粒试点工作结束及质量标准制定技术要求实施后,国家及省级中药配方颗粒标准的制定均取得了阶段性成果。梳理了中药配方颗粒国家标准的研究历程及省级标准的探索研究成果,以山东省中药配方颗粒标准制定过程中的标准复核及审评中遇到的问题为切入点,主要包括药材基原、生产工艺、定性/定量指标成分合理性等问题,挖掘了上述问题产生的具体原因,提出了做好中药配方颗粒源头把控、寻求更加专属经济的检验方法、强化生产全过程质量控制,以及构建以企业为核心、相关各方应合作共享的质量标准制定体系等建议,推动中药配方颗粒标准的制定和完善,以期促进中药配方颗粒产业的高质量发展。     

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??OBJECTIVE To establish the International Pharmacopoeia standard for norethisterone tablets. METHODS In accordance with the requirements of the International Pharmacopoeia standard, the existent quality standards of norethisterone tablets and related literatures were referred, appropriate methods were selected, and verification test was carried out to determine the best method. RESULTS In the system suitability test of thin layer chromatography identification, the spots of norethisterone and ethinylestradiol were separated well. Nine known impurities and other unknown impurities could be separated well by the HPLC method for the examination of related substances, and the impurity with relative retention time of 1.1 was shown to be ethinylestradiol by LC-MS. In 0.1 mol??L^-1 hydrochloric acid solution containing 0.09% SDS, norethisterone tablets achieved a dissolution of more than 90% in 30 min and the dissolution curve reached plateau. Under the liquid chromatographic condition for the assay, the linear range was 0.746-29.840 ??g??mL^-1 (r=0.999 9),and the resolution between norethisterone and ethinylestradiol was over 4.0. CONCLUSION The established quality standard of norethisterone tablets is simple and accurate, which fully considers the feasibility of the method and accessibility of reagents, thus can effectively control the quality of products.     

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??OBJECTIVE To analyze the trend in quality control of anti-HER2 monoclonal antibody.METHODS The biological activity of anti-HER2 monoclonal antibody (mAb) was monitored by the proliferation inhibition with CellTiter 96^?kAQ_ueousAssay kit using BT-474 cells as target, and the potency of anti-HER2 mAbs was calculated by comparison with the reference standard using the method of parallel analysis.Cation exchange chromatography method was used to detect the purity by calculating the area percentage of the main peak according to the area normalization method.Ultraviolet spectrophotometry was used to detect the protein content. And pH was detected by potential method. The warning limit(??2s)and action limit(??3s)were defined according to the determination results of several batches of anti-HERmAb by National Institutes for Food and Drug Control(NIFDC)and the quality control laboratory of manufacturer, based on which the trend graph was plotted, and the consistent and periodic trend of anti-HER2 mAb were analyzed.RESULTS The potencies of 74 batches of anti-HER2 antibodies from a certain enterprise during 2012 to 2014 were analyzed. The products and reference standard both showed a dose-response effect in biological activity, presenting parallel straight lines on semi-log coordinate paper.The potencies determined by NIFDC and the manufacturer were (1.04??0.11)??10⁴ and (0.94??0.08 )??10⁴ U??mg^-1, respectively. And the protein contents were (442.15??13.59) and(442.07?? 6.60) mg??vial^-1.The main peak areas of IEC-HPLC were(76.29??1.36)% and (73.76??1.17)%, while the pHs were (6.16??0.11) and (6.22??0.08), respectively. The consistent and periodic trend analysis of the above-mentioned results showed that the total trend was relatively steady. CONCLUSION This is the first time to conduct trend analysis of critical quality attributes (CQA) of anti-HER2 monoclonal antibody. These results reveal the quality changes of the products,which would help a lot in evaluating the batch consistency and production stability, and also provide reference for trend analysis of critical quality attributes for other monoclonal antibodies.