Analytical data of designated substances (Shitei-Yakubutsu) controlled by the Pharmaceutical Affairs Law in Japan, part II: Color test and TLC

Many psychotropic substances are readily available in Japan via the Internet. To avoid the spread of drug abuse, some drugs have been controlled as designated substances (Shitei-Yakubutsu) in Japan since 2007 by the Pharmaceutical Affairs Law. Twenty-nine designated substances (classified as tryptamine, phenethylamine and piperazine types) were analyzed using color tests and TLC. The color tests were examined with the Marquis, Ehrlich, Simon's, Liebermann-Burehard's, and Mandelin reagents. The color of beta-carbonyl-methylenedioxyphenetylamines produced by the Marquis reagent was yellow, and 4-halo-2,5-dimethoxy phenethylamines reacted with the Marquis reagent to a give deep yellow-green and/or a deep green color. Although all designated substances of the tryptamine type reacted with the Ehrlich reagent to give a brown color, only 1-(2,4,6-trimethoxyphenyl) propan-2-amine (TMA-6) among the phenethylamines showed a red color on treatment with the reagent. However, 3,4,5-trimethoxy and 2,4,5-trimethoxy isomers of TMA-6 were not colored with the reagent. Thus, TMA-6 could be distinguished from isomers using the Ehrlich reagent. We also analyzed the designated substances with thin-layer chromatography developed with two different solvent conditions. All substances were detected by UV(254 nm) and an iodoplatinate reagent. These results suggest that color tests and TLC, followed by GC-MS and LC-MS analyses, can be used for preliminary identification of designated substances.     

Social change and Pharmaceutical Affairs Law (PAL)

Former Japanese pharmaceutical laws, originally based on the Pharmaceutical Marketing and Handling Regulations enacted in 1874 were in operation for many years before World War II. However, in order to address several drug issues, such as poor drug quality and insufficiences regarding the role of pharmacists during the War, the laws needed to be unified and revised. In this paper, we analyzed the record of discussions held by the Imperial Diet on the bill for the Pharmaceutical Affairs Law (PAL) in 1943. This is also regarded as the origin of the current PAL (LawNo.145 in 1960). Through this analysis, we tried to clarify the relationship between the social change and the role of PAL in society. During the War, the bill was discussed, aiming at the improvement of both human resources who treated drugs, and the quality of drug materials. Diet members discussed three main points, namely, "the duty of pharmacists", "the mission of the Japan Pharmaceutical Association" and "the quality control of pharmaceutical products". Notably, the bill pharmacists are required not only to dispense drugs, a role they had previously, but also to manage drug and food hygiene through the quality control of pharmaceutical products and the inspection of food and drink, in order to improve the public health in Japan. Originally, the law was passed to deal with the extraordinary circumstances during the War, but through our analysis, we found that they proactively improved the role of the law to comply with various drug issues raised during the War, the rapid change of the pharmaceutical hygiene concept and the social transformation.     

从日本药事法的修订谈我国境外药品委托生产

目的:为我国制药企业发展境外药品委托生产提供参考。方法:对比我国和日本等国药品委托生产注册制度,在分析我国药品委托生产现状的基础上,对我国制药企业承接来自日本等国的境外药品委托生产的可行性进行分析。结果与结论:我国政府和制药企业应抓住日本药事法修订的机遇,创造更有利的条件,力争在境外药品委托生产中有所作为。     

Evaluation for skin sensitization based on published literatures (existing information) of major PRTR designated chemical substances in Japan

Of the 354 substances designated as class I under the Pollutant Release and Transfer Register (PRTR) law in Japan, we reviewed the sensitization data of the selected 144 substances and analyzed it from various aspects comparing human and animal data, determining the relationship between skin sensitization and chemical structure and comparing the various international organizations.Although most of them were expected to be hazardous substances, 49 out of the 144 substances lacked both human and animal sensitization data. Positive substances accounted for 69% and 42% of the substances for which sensitization data were available in the case of humans and animals, respectively.A correlation was observed between the chemical structures of the substances and sensitization, despite the relatively few substances examined in this study and the limited homogeneity of the collected data. In particular, epoxides clearly had sensitizing potentials and more than half of carboxylic esters or dicarboxyl anhydrides, aliphatic aldehydes, and aromatic compounds with at least two hydroxyl groups also had sensitizing potentials.Also, this study clearly demonstrated the lack of consistency across the sensitization assessment criteria adopted by different countries or among those adopted by the same country on the basis of different laws or administrative measures.     

LC-MS法分析拉米夫定的有关物质

目的建立检测拉米夫定中有关物质的液质联用分析方法,分析鉴定拉米夫定原料药、加速破坏样品和制剂产品中的有关物质,并推测其可能的降解途径。方法色谱柱为Syncronjs C_(18)柱,以5 mmol·L^(-1)乙酸铵-甲醇为流动相,线性梯度洗脱,对拉米夫定有关物质进行分离。分别在正负离子模式下采用一级全扫描和自动二级全扫描方式对样品进行质谱检测。结果拉米夫定及其各有关物质分离良好,共检测到13种有关物质。结果表明,拉米夫定的主要降解反应为氧化、差向异构化、脱氨和水解。在酸性和高温条件下,药物的稳定性良好,但在碱性和氧化条件下,药物稳定性较差。制剂产品中有关物质的种类较原料药有显著增加。结论该方法适用于拉米夫定有关物质和降解途径的研究,试验中检测到的有关物质,推测的降解途径及该类物质的质谱行为规律为该产品的质量控制及稳定性研究提供了重要的依据。     

LC-MS法鉴定头孢特仑新戊酯中的有关物质

目的建立鉴定头孢特仑新戊酯中有关物质的液相色谱-质谱联用分析方法,测定头孢特仑新戊酯原料药和制剂产品中的有关物质。方法采用Syncronis C18(250 mm×4.6mm,5μm)色谱柱,10mmol·L-1乙酸铵-乙腈(体积比50∶50)作为流动相等度洗脱分离;采集各有关物质的UV谱、一级和二级质谱图,并根据所得信息对有关物质进行结构分析。结果头孢特仑新戊酯原料药中检测到8种有关物质,分别为6种合成副产物、1种水解产物和1种降解产物;制剂产品中除原料药中的8种有关物质外,还检测到4种新的有关物质,分别为2种氧化产物、1种水解产物和1种降解产物。结论该方法灵敏度高,全面系统的阐述了头孢特仑新戊酯中的有关物质,为其质量控制和工艺优化提供了参考依据。     

Pharmacovigilance in developing countries (part I): importance and challenges

The thalidomide disaster was the significant historical event that acted as a catalyst for pharmacovigilance activity. Following this event developed countries initiated drug monitoring systems that evolved and now extend their scope to broader drug-related safety issues; however, this was not the case in developing countries. Pharmacovigilance is still a relatively new concept with low priority in developing countries although various issues are raising concerns that magnify the need for systems to monitor post marketing drug safety in these countries. This article analyzes the barriers to introducing robust pharmacovigilance systems in developing countries.     

LC-MS/MS法鉴定注射用多西他赛中的有关物质

采用LC-MS/MS法对注射用多西他赛中的有关物质进行鉴定。采用乙酸乙酯提取注射剂,以去除制剂中影响LC-MS/MS离子化效果的磺丁基-β-环糊精等辅料,然后对提取物中的有关物质进行LC-MS/MS鉴定。采用LC-ESI-MS/MS测定各有关物质的一级和二级质谱图,并对准分子离子的各个产物离子进行归属,对各杂质可能的结构进行推测。在所建立的条件下,多西他赛及其有关物质分离良好,共鉴定了注射用多西他赛中的9个有关物质结构,其中4个有关物质为首次在注射用多西他赛中发现。本文所建立的LC-MS/MS法可以有效地分离分析多西他赛及其有关物质,为其制剂的质量控制和工艺优化提供参考。     

Pharmaceutical Research Reviewers for the Editorial Office,Japan (October 1992-September 1993)

Pharmaceutical Research Reviewers for the Editorial Office, Japan (October 1992-September 1993)     

Performance in population models for count data,part I: maximum likelihood approximations

There has been little evaluation of maximum likelihood approximation methods for non-linear mixed effects modelling of count data. The aim of this study was to explore the estimation accuracy of population parameters from six count models, using two different methods and programs. Simulations of 100 data sets were performed in NONMEM for each probability distribution with parameter values derived from a real case study on 551 epileptic patients. Models investigated were: Poisson (PS), Poisson with Markov elements (PMAK), Poisson with a mixture distribution for individual observations (PMIX), Zero Inflated Poisson (ZIP), Generalized Poisson (GP) and Negative Binomial (NB). Estimations of simulated datasets were completed with Laplacian approximation (LAPLACE) in NONMEM and LAPLACE/Gaussian Quadrature (GQ) in SAS. With LAPLACE, the average absolute value of the bias (AVB) in all models was 1.02% for fixed effects, and ranged 0.32–8.24% for the estimation of the random effect of the mean count (λ). The random effect of the overdispersion parameter present in ZIP, GP and NB was underestimated (−25.87, −15.73 and −21.93% of relative bias, respectively). Analysis with GQ 9 points resulted in an improvement in these parameters (3.80% average AVB). Methods implemented in SAS had a lower fraction of successful minimizations, and GQ 9 points was considerably slower than 1 point. Simulations showed that parameter estimates, even when biased, resulted in data that were only marginally different from data simulated from the true model. Thus all methods investigated appear to provide useful results for the investigated count data models.     

HPLC法测定糠酸莫米松乳膏中的有关物质

目的 建立糠酸莫米松乳膏(艾洛松)中有关物质的检测方法。 方法 采用HPLC法对艾洛松中的有关物质进行测定。以Amethyst C₁₈-P(250 mm×4.6 mm,5 μm)色谱柱为固定相;乙腈-水(53∶47)为流动相;流速为1 mL·min-1;检测波长为254 nm;进样量为20 μL。 结果 各单个杂质不超过1.0%,总杂质不超过2.0%。该方法对5个批次糠酸莫米松乳膏中的有关物质进行了测定,其限度均为单个杂质不超过1.0%,总杂质不超过2.0%。 结论 该方法准确可靠,可作为糠酸莫米松乳膏(艾洛松)中有关物质的测定方法。     

我国执业药师考试“药事管理与法规”试题分析

运用X~2检验方法对1995年、1996年、1997年全国执业药师资格考试“药事管理与法规”试题进行了分析、讨论,表明3年掌握、熟悉、了解的内容符合考试大纲的要求,试题总体质量较高。针对试卷中存在的问题,提出了建议,旨在为提高试题质量和考生通过率提供参考。     

LC-MS/MS法分析注射用头孢西丁钠中的有关物质

目的:建立LC-MS/MS法分析注射用头孢西丁钠中的有关物质。方法:采用Thermo Syncronis C18(4.6 mm×250 mm,5μm)色谱柱,以1%甲酸水溶液(A)-乙腈(B)为流动相,1.0 mL.min-1线性梯度洗脱分离;柱后分流,电喷雾离子化MS测定。采集有关物质的PDA谱、质谱母离子及子离子谱,并进行解析,推测有关物质的结构。结果:在所建立的条件下,头孢西丁钠及其有关物质分离良好,检测出15个有关物质,并对其进行结构解析。结论:建立的LC-MS/MS法能有效地分离分析头孢西丁钠及其有关物质,为注射用头孢西丁钠的质量控制和工艺优化提供了参考。     

The Pharmaceutical Sciences in 2020: Report of a Conference Organized by the Board of Pharmaceutical Sciences of the International Pharmaceutical Federation (FIP)

The Board of Pharmaceutical Sciences (BPS) of the International Pharmaceutical Federation (FIP) has developed a view on the future of pharmaceutical sciences in 2020. This followed an international conference with invited participants from various fields (academicians, scientists, regulators, industrialists, venture capitalists) who shared their views on the forces that might determine how the pharmaceutical sciences will look in 2020. The commentary here provides a summary of major research activities that will drive drug discovery and development, enabling technologies for pharmaceutical sciences, paradigm shifts in drug discovery, development and regulations, and changes in education to meet the demands of academia, industry and regulatory institutions for pharmaceutical sciences in 2020.     

我国近现代药事管理体制的演变与发展

1清末时期医药卫生机构的设立及医药法规 1898年清政府在上海市公共租界内设立卫生处,为西方国家派遣来我国的各种侨民服务.1900年天津设立的都统衙门附有卫生局,管辖地方卫生工作.以后,由清廷收回自办,改称北洋局.这是我国地方卫生行政组织的开端.     

中国、美国、日本医药产业创新体系的对比研究

通过分析、比较美国、日本、中国的医药产业创新体系,从中得到启示,建议政府通过调控和扶持医药企业成为创新主体,并重视投资大学和科研机构,促进我国医药产业创新体系的发展.     

我国药事管理结构体系探讨

本文着重探讨了我国药事管理结构体系，并提出了初步创新设想和前景展望。