浅谈仪器分析在制药工程中的应用.doc

this type of operation for the safety technology. Without education and training in safety knowledge, shall not enter the construction site operations. To enter the construction site, you must wear a helmet, buckle chinstrap. Work at two meters high and must be fastened. When working at height, are not allowed to throw down or up the materials and tools and other objects. Persons not engaged in electrical and mechanical, prohibited the use of mechanical and electrical equipment. Building materials and components to be tidy and secure, shall not exceed the relevant provisions. Hazardous areas should be clearly marked, protective measures should be taken at night to set up a red light warning. In the operation, should adhere to their jobs, drunken operation is strictly prohibited. Special operations personnel (electricians, welders, boiler operators, blasters, lifting grid and pile drivers and commanding, shelf workers, machines, motor vehicle drivers, and so on) must be operating permits from the relevant sector professional training examinations, independent operation, operation focus, not to leave. Construction site prohibited to wear slippers, heels, skirt, sliding and studded shoes and barefoot, shirtless, and so on. Construction site of the scaffold (prohibition of the use of bamboo and wood materials setting), protective equipment, safety signs, warning signs, scaffolding wall may be supplemented, removed and need to be removed must be reinforced by the contractors agree. Construction site of the four (openings, stairs, lift head, hole) and the five-limb (balcony, framing, roofing, run (oblique) road and unloading platforms), protective measures and clearly marked. Are not allowed to sit at the feet of . Nails should be promptly removed. Drywall cut bricks are cut, no outside chopping. Preventing broken tiles fall hurt. Tools must always be mounted after good tool bag. In the Derrick (gantry) travel; in the Derrick (gantry) increased security measures are not taken to the following cleaning mortar, concrete and other debris; hanging baskets for a long time is not allowed to stop the air; after work basket must be placed in the ground, and cut off the power and lock box. Scaffolding on the Frost, snow, mud, and building waste time cleaning. Both ends of the scaffold to fasten to prevent probe Panel. Danger of overloading the scaffold: laying per square foot scaffold distributed load shall not exceed 270KN, piled up on the scaffold standard bricks of single side three storeys high. Wall removal of dangerous scaffolding; Sat down to rest on the guard rail danger; Set, dismantling scaffolding, Derrick (gantry) high, edges, vacant jobs, such as not wearing a seat belt at risk. Upper part of the ladder to fasten, antiskid measures are required in the lower part. Upper part of the ladder to hang, and lower banding. Ladder to fasten in the Middle, lower to have a non-slip steps, are not allowed to sit on it, riding moves. Altitude: personnel engaged in the Spider-man,stavebn tm vdce mst een. een by mlo zahrnovat analzu rizik, monost nehod charakteristik a nouzovch postup, nouzov zpracovn a obsah opaten. 4, integrovan pohotovostn plny, speciln havarijn plny a mst een by mly bt mezi sebou a s ostatnmi jednotky zapojeny v nouzi, kter jsou vzjemn propojeny. 5, havarijn pln by ml zahrnovat havarijn personl a organizace kontakt, nouzov rezervn seznam a dal informace. Informace by mly bt pravideln aktualizovny a zajist, e informace jsou pesn a platn. tyi, havarijn pln revize 1, Recenze pohotovostn plny pezkoumn formul a prvky pezkumu a opaten pijatch dvma zpsoby. Kdy host slou pedevm pro havarijn plny pro zznam v podob Recenze, prvek hodnocen pro nouzov hodnocen. . 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Antistatick opaten, jako jsou zazen, potrub, by mlo bt v souladu s technickmi pedpisy pro uzemnn design pro chemick podniky pslunch ustanoven. 7. nhl vbun petlaku nebo rychlho rozkladu vrobnch zazen nebo skladovacch zazen by mly bt vybaveny vbuchu (nevbun membrna), vvoz nonel trubice smrem k bezpenosti a aby prevence sekundrnch exploz, protiporn opaten. 8. vrobnthe principle of simplified EIA of construction projects in the region. In terms of land, linked to the implementation of urban and rural construction land increase and decrease, replacement indicators for priority areas project. Charges, into the projects of water, electricity, administrative charges and preferential policies. In the area of taxation, and settled in areas of industry and its production company, within 5 years after the completion of fiscal incentives to enterprises. In terms of financing, integration of land, tax, financial and other resources, and construct Government credit + business credit credit system, establishment of marketization, commercialization and modernization of the investment and financing platform; effective Bank-enterprise docking, encourages private capital into the Park, to raise industry development fund. 5, optimize the environment and service industries. To create policy lowlands, Highlands, integrity of service land, development land as the goal, to optimize the area under development environment. All administrative law enforcement departments to appoint a full-time personnel stationed in areas dedicated to coordinating and solving problems associated with businesses in this sector. When there are substantial issues, sector leaders arranged to personally intervene, in-person, in-person push tangible area building a green light, easy line. To further reduce and standardize administrative examination and approval items, simplify examination and approval links, improve efficiency; according to the .Since the educational practice of the mass line of the party, himself seriously in the education, practical control central eight rules and opposing the four winds and practicing three Suns, and check the spirit of Jiao Yulu, ideology, solicit opinions based on outstanding problems checked swing, careful analysis and reflection. Will now check report is as follows: first, adherence to the partys political discipline, eight in the central provision, change the style of the basic situation of 1, in compliance with the partys political disciplines. Conscientiously abide by the partys political discipline, abide by the Constitution and the rules and regulations of the party, in the political, ideological and maintain highly consistent with the CPC Central Committee on the action, there is no violation of the partys political discipline problems. 2, in the implementation of the central authorities of the eight provisions. Improving research, improving research methods, but there are less grass-roots units, primary first-hand an inadequate grasp of the problem, which is to be strengthened in the future. Second, construction, strictly in accordance with the provisions to streamline and improve the quality of meetings of the Conference. Third, streamlining file briefs, culture involves all aspects of propaganda and ideology, sometimes due to the practical needs of invention notifications, this area needs further浅谈仪器分析在制药工程中的应用（程志全 武汉科技大学中南分校）摘要：通过对严拯宇等人编著的仪器分析(第二版）的解读，以及结合相关书刊的知识，对仪器分析在制药领域中的应用，做了一个初步而较全面的认识和分析。仪器分析是现代制药工程中一项必不可少而重要的方法和途径，通过这种科学手段，我们可以全面而系统地建立药物制剂研发、生产、治疗的质量监管体系，以保证人民用药稳定、安全和有效。关键词：仪器分析 应用 制药工程 质量 监管引言：通过对较多文献的查阅，发现很少有专门来谈仪器分析在制药领域中应用的文献。本文正是基于这种原因，也是在这门课程的学习中，发现仪器分析的原理和方法较多，很多同学学完之后都难以将它们比较系统的归纳起来。于是，通过解读教材和相关书刊，写出这篇综述。正文：作为制药工程专业人才的我们，需要具备药物分析及检测方向的专业素质，学会仪器分析药物、波谱分析、药物分析和天然药物分析与分离课程基本理论，熟悉常见药物检测的操作与方法。同时，我们也要掌握职位工作描述与产品生产、研发、检测、营销、环境保护、管理相关的波谱分析、高级仪器分析等核心能力与技巧，精通仪器分析常见药品技术，能胜任大型药厂、大型医院、药品检测中心等相关企事业单位的检测、研发、管理的工作。可见掌握化学分析、仪器分析基本理论对制药工程的学习是非常重要的。 现在，我和大家一起探讨一下仪器分析在制药工程中的应用，从而加深对制药工程的理解和认识。近年来，仪器分析飞速发展，新方法、新技术、新仪器层出不穷，仪器分析的应用也日益普遍。仪器分析逐渐向药学、医学、生物学等领域渗透，特别是在新药研究、药物分析、临床检验、病因研究等方面都大量使用了仪器分析方法，其在药学专业中的重要地位日渐突。下面是我和大家一起探讨仪器分析在制药工程中关于药物成分的检测、分离和分析等应用。仪器分析大致可以分为电化学分析法、光谱分析法、色谱分析法和核磁共振波谱法。接下来，我将从这四个方面描述其应用。1. 电化学分析法 电化学分析法包括电解法、电导法、电位法、伏安法。其中，电解法在分析中除作为测定方法外，还作为一种分离方法使。许多电化学分析法，既能分析有机物又能分析无机物，是仪器分析的一个重要组成部分，在生产、科研、医药卫生各个领域有着广泛的应用。 今后还会出现许多新方法，尤其在本身自动化和与其他分析方法联用技术方面，将 会得到更快的发。2. 光谱分析法（1） 紫外可见分光光度法（UV-Fri) 紫外可见分光光度法（UV-Vis)在药学领域中主要用于有机化合物的分。多 数有机药物由于其分子中含有一些有共轭的不饱和基团，而能吸收紫外可见光，可 以显示吸收光谱。不同的化合物可有不同的吸收光谱。利用吸收光谱的特点可以进行 药品与制剂的定量分析、纯物质的鉴别及杂质的检测。在药品和制剂生产中，我们可 以用这种方法来对药品成分进行分析，以确保药品质量的可靠。中国药典（2005版） 中用这种方法对维生素进行鉴定：维生素有3个吸收峰278nm、361nm及550nm 且 如果被鉴定物的吸收峰和对照品的相同，且峰处 吸收度或吸光系数的比值又在规定范围之内，则可考虑被测样品与对照品分子结构基 本相同。 此方法由于不需要复杂的分离，所以方法比较简便。 （2）荧光分析法 虽然具有天然荧光的物质数量不多，但许多重要的药物都有荧光现象。而荧光衍生化试剂的使用，又扩大了荧光分析法的应用范。 荧光分析可作初步鉴别及含量测定，目前，广泛应用于医药学，特别适用于药物在 体液中的浓度测定及药物在体内代谢过程的研究。如测定复方炔诺酮中炔雌醇含量，我们可以通过荧光光谱法，与炔雌醇对照品同法测定，计算即得。 （3）红外光谱法（IR） 红外分光光度法的用途可概括为定性鉴别、定量分析及结构分析等。因红外光谱 的高度特征性，在药物分析中，用于鉴别组分单一、结构明确的原料药，是首选方。 在药物分析中，各国药典均将红外光谱法列为药物的常用鉴别方法并对晶型和异 构体区分提供有用信。中国药典（2005年版）中药物的红外光谱鉴别大多采用与 标准图谱对比法，标准图谱为与药典配套出版的药品红外光谱。 在定量分析方面，红外光谱上可供选择的波长较多，但操作比较麻烦，准确度也 比紫外分光光度法低，除用于测定异构体的相对含量外，一般较少用于定量分。 （4）原子吸收分光光度法（AAS） 原子吸收分光光度法是测金属离子定量测定的首选方法。有些药物分子结构中含 有金属原子，例如，维生素含有钴原子，可测定钴的含量，一以求得维生素含 量；而有些有机药物虽然不含金属离子，但是可以使其与金属离子生成金属配合物， 然后用间接法测定有机物，如8-羟基喹啉可制成8-羟基喹啉铜，溴丁东莨菪碱可制成 溴丁东莨菪碱硫氰酸钴，分别测定铜和钴的含量，即可分别求得8-羟基喹啉和溴丁 东莨菪碱的含量。 原子吸收分光光度法具有测定灵敏度高、检出限低、干扰少、操作简单、快速等 优，已广泛应用于食品分析和药物分析等领域中。 3.色谱分析法 （1）薄层色谱法（TLC） 薄层色谱法（TLC）广泛应用于各种天然和合成有机物的分离和鉴定。在药品质量控 制中，可用于测定药物的纯度和检查降解产物，并可对杂质和降解产物进行限度试验。在 生产上可用于判断反应的终点，监视反应历程。薄层色谱广泛应用于中药和中成药的鉴别， 并可进一步进行含量测定。 TLC薄层色谱鉴别已成为中药质量控制中鉴别的首选方。 2005年版中国药典（一部）新增专属性TLC鉴别662项。在能增加专属性强的TLC鉴别的情况下，则删去原有的化学反应鉴别，如复方鱼腥草片、复方丹参滴丸、苏和香丸等。 （2）气相色谱法（GC） 气相色谱法（GC）在药物分析中的应用很广泛，包括药物的含量测定、杂质检查及有机溶剂的残留量、中药成分研究、制剂分析、治疗药物监测和药物代谢研究。中国药典2005年版一部中，气相色谱被应用于中药中挥发性成分的含量测定，如桉油中桉油精、麝香中麝香酮、丁香中丁香酚、肉桂油中桂皮醛等测定。药品中残留有机溶剂普遍采用气相色谱法测定。若样品中残留溶剂种类较多，沸点相差较大，可采用程序升温的毛细管GC法，色谱分辨率明显优于填充柱。 （3）高效液相色谱法（HPLC）高效液相色谱法（HPLC）主要用于复杂成分混合物的分离、定性与定量。由于HPLC分析样品的范围不受沸点、热稳定性、相对分子质量大小及有机物与无机物的限制，一般说来只要能制成溶液就可分析。因此，HPLC的分析范围远较GC广泛。2005年版中国药典收载的成方制剂及单味制剂564个品种中，有438个建立了含量测定，采用HPLC等仪器分析方法的为412。HPLC正成为药物制剂含量测定的首选方法，也是每个制药工程专业毕业生所应该掌握的方法。2000年版中国药典采用水蒸汽蒸馏提取丹皮酚水溶液，然后用可见-紫外分光光度法测定吸收度，以确定含量，方法专属性不强，现改为HPLC法测定，方法精确、专属性。2000年版以前中国药典采用TLCS测定山茱萸中的熊果酸含量，原含量检测指标专属性不强、处理方法繁琐，需要23d的时间才能处理完，这次改为超声提取后用HPLC测定山茱萸的特有成分马钱苷，方法简便、快。连同六味地黄系列中成药均由熊果酸改测马钱苷，从而使长期困扰经典名药六味地黄系列中成药的山茱萸假冒问题有望得到根本解。HPLC的梯度洗脱，能简化分析方法，缩短分析时间，同时测定样品中的多种成分，提供样品更多的信息，从而达到整体控制药品质量的目。此外，由PE公司PerSeptive Biosystems蛋白质研究中心于1989年推出的生物大分子高效液相色谱分离的方法贯流色谱（PC），由于其特殊的两套孔系统（在这一色谱基质中的对流孔直径比高分子棒小，而其扩散孔直径要比硅胶棒的直径大约5-40倍），使得其在蛋白质、多肽和核苷酸从分析到制备范围内有很大的改进。贯流色谱填料非常适合于生物大分子制备和分离，被PE公司认为是生化分离技术的革命性进展，大大增强了工作效率，提高产品质量，降低了下游成本，大大缩短了新药研发时。（4） 微柱液相色谱法 近十几年来，有关微柱液相色谱的研究十分活跃。与普通液相色谱相比，微柱液相色谱由于用微柱代替了常规色谱柱，分析所需样品量以及流动相消耗大大下降，而且样品柱内扩散成几何级数降低，从而提高了检测器灵敏度，使检测效果更为理想。因此，它也广泛用于药物领。 它可以进行快速药物分析，尤其是对复方制剂分析和治疗药物监测非常适用。利用色谱法分离分析成分复杂中药的有效成分时，色谱柱的寿命会大大缩短，而微柱价廉有只需少量的填料即可获得较高的柱效。用微柱可以成功分离紫花洋地黄叶中的洋地黄A、B和葡萄糖吉托洛苷等成分。 4. 核磁共振波谱法（NMR） 核磁共振波谱与紫外可见光谱及红外光谱的主要不同点是由于照射波长不同而引起的跃迁类型不同。氢谱和碳谱是有机化合物结构测定最重要的两种核磁共振波谱，两者可互为补充。氮15NMR用于研究含氮有机物的结构信息，是生命科学研究的有力工。核磁共振波谱可测定有机物质的化学结构及立体结构，研究互变现象，对新药研发和构效研究是很重要的手段；还可以测定某些药物的含量及纯度检查，如英国药典1988奶奶版规定庆大霉素用NMR法鉴定；而且，由于这种方法具有能深入物体内部而不破坏样品的特点，对生物化学药品有广泛应用，如药物与受体间的作用机制研。此外，质谱法（MS）常与UV、IR和NMR联合使用，是有机化合物结构分析的重要工具之一；它与色谱联用后，可用于多组分的定性和定量：采用选择离子检测（SIM）技术可获得非常高的灵敏度和选择性，是目前痕量有机分析最有效的手段之。各类分析仪器的联用，特别是分离仪器和检测器的联用，如色谱仪和各种分析仪器的联用，使前者的分离功能和后者识别功能很好地结，这是仪器分析的发展方向，也将是仪器分析在制药领域中应用的趋势。结论：通过对课本和相关书刊的解读，并结合中国药典，本文从较全面的角度初步阐述了仪器分析在制药工程中的应用。本文谈到仪器分析的五个方面，这五个方面是仪器分析的基本组成部分。通过各项方法的认识和区别，我们知道每一种方法在制药领域中的应用也有所不同。此外，本文加深了对仪器分析这门课程的认识，更结合了制药专业特点，对各种方法做了大致的论述。致谢：感谢薛永萍老师和刘阳老师的指导！参考文献：1王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪. 前言M. 仪器分析(第二版）, 2009.2、3王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 电化学分析概述M 仪器分析(第二版）2009：1-24王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 紫外可见分光光度法 定性与定量分析方法M 仪器分析(第二版）2009：405王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 荧光分析法概述 M 仪器分析(第二版） 2009：616、7、8王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 红外分光光度法应用与示例 M 仪器分析(第二版） 2009：1021079王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 原子吸收分光光度法应用与示例M仪器分析(第二版） 2009：13110张彤，陶建生，徐莲英.中药制剂分析教学内容的创新与完善J 中成药2007,29(3):430. 11王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 气象色谱法应用与示例M仪器分析(第二版） 2009：258-26012、15、16钱忠直.2005年版中国药典中药标准的变化J.中药研究与信息，2005，7（7）：5. 13陈钢，陈桂良，潘维芳.中国药典2005年版增修订情况简介J.上海医药，2005，26（8）：34514、17张彤，陶建生，徐莲英.中药制剂分析教学内容的创新与完善J中成药2007,29(3):43218 喻昕，赵睿，喻格书 多肽及蛋白质类药物的分离M生物药物分离技术2008：9810319 王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 微柱液相色谱法M 仪器分析(第二版） 2009：28520、21 王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 核磁共振波谱法概述M 仪器分析(第二版） 2009：138-14022 王志群，严拯宇，杜迎翔，肖莹，何华，沈卫阳，钟文英，倪坤仪 质谱法概述M 仪器分析(第二版） 2009：175-17623杨秀梅 仪器分析方法与分析仪器主要特点及发展现状综述J生命科学仪器 2010，8（5）：43英文摘要：Abstract:Based on YanZhengYu person such as the book of instrument analysis (second edition), and the interpretation of knowledge according to relevant books,a preliminary and comprehensively understanding and analysis of instrument analysis applications in the field of pharmaceutical engineering was made. Instrument analysis is one of the indispensable modern pharmaceutical engineering and important methods and ways.Through this scientific methods,a drug preparation research and development,production,the treatment quality supervision system is comprehensively and systematically established,to ensure the peoples drug stability,safety and effective.Key words:instrument analysis application pharmaceutical engineering quality supervisionthis type of operation for the safety technology. Without education and training in safety knowledge, shall not enter the construction site operations. To enter the construction site, you must wear a helmet, buckle chinstrap. Work at two meters high and must be fastened. When working at height, are not allowed to throw down or up the materials and tools and other objects. Persons not engaged in electrical and mechanical, prohibited the use of mechanical and electrical equipment. Building materials and components to be tidy and secure, shall not exceed the relevant provisions. Hazardous areas should be clearly marked, protective measures should be taken at night to set up a red light warning. In the operation, should adhere to their jobs, drunken operation is strictly prohibited. Special operations personnel (electricians, welders, boiler operators, blasters, lifting grid and pile drivers and commanding, shelf workers, machines, motor vehicle drivers, and so on) must be operating permits from the relevant sector professional training examinations, independent operation, operation focus, not to leave. Construction site prohibited to wear slippers, heels, skirt, sliding and studded shoes and barefoot, shirtless, and so on. Construction site of the scaffold (prohibition of the use of bamboo and wood materials setting), protective equipment, safety signs, warning signs, scaffolding wall may be supplemented, removed and need to be removed must be reinforced by the contractors agree. Construction site of the four (openings, stairs, lift head, hole) and the five-limb (balcony, framing, roofing, run (oblique) road and unloading platforms), protective measures and clearly marked. Are not allowed to sit at the feet of . Nails should be promptly removed. Drywall cut bricks are cut, no outside chopping. Preventing broken tiles fall hurt. Tools must always be mounted after good tool bag. In the Derrick (gantry) travel; in the Derrick (gantry) increased security measures are not taken to the following cleaning mortar, concrete and other debris; hanging baskets for a long time is not allowed to stop the air; after work basket must be placed in the ground, and cut off the power and lock box. Scaffolding on the Frost, snow, mud, and building waste time cleaning. Both ends of the scaffold to fasten to prevent probe Panel. Danger of overloading the scaffold: laying per square foot scaffold distributed load shall not exceed 270KN, piled up on the scaffold standard bricks of single side three storeys high. Wall removal of dangerous scaffolding; Sat down to rest on the guard rail danger; Set, dismantling scaffolding, Derrick (gantry) high, edges, vacant jobs, such as not wearing a seat belt at risk. Upper part of the ladder to fasten, antiskid measures are required in the lower part. Upper part of the ladder to hang, and lower banding. Ladder to fasten in the Middle, lower to have a non-slip steps, are not allowed to sit on it, riding moves. Altitude: personnel engaged in the Spider-man,ch z