液相色谱与质谱联用技术在药物研究中的应用

液相色谱和质谱联用（LC—MS）技术将色谱的高分离性能和质谱的高选择性相结合,具有检测样本多样性、重复性好,是一种高效快速、高选择性、高灵敏度的新型分离分析技术,非常适合活性成分复杂、含量低的药物研究。本文综述了液相色谱与质谱联用技术近年来的发展和在药物研究中的应用,该技术已成为药物研究和质量控制的有效手段之一。     

液相色谱-质谱/串联质谱联用技术及其在药物分析中的应用

液相色谱-质谱联用技术结合了色谱、质谱两者的优点，将色谱的高分离性能和质谱的高鉴别特点相结合，组成了较完美的现代分析技术。本文介绍近年来液相色谱-质谱接口技术的研究进展及液相色谱-质谱／串联质谱联用技术等在药物分析中的应用，包括药物研究的分离与鉴定，药物动力学研究的体内浓度分布、代谢物分析等，展示了它的发展前景。随着液相色谱-质谱接口技术的不断完善，液质联用技术将在药物分析中占据越来越重要的地位。     

液质联用技术在抗生素分析中的应用

液质联用技术是将液相色谱与质谱串联的检测技术,具有灵敏度高、选择性好、分离能力强和高通量筛查的优点,已成为药物分析的关键技术和研究手段.通过简要综述了抗生素发展、应用中存在的问题以及液质联用技术在抗生素杂质研究、滥用残留及代谢方面的应用,为抗生素质量控制和合理使用提供相关理论参考.     

微透析与液相色谱-质谱联用在药物分析中的应用

目的综述微透析与液相色谱-质谱联用技术在药物体内化学成分分析中的研究进展。方法参阅近几年国内外相关文献,对微透析与液相色谱-质谱联用技术在药物体内内源性物质及外源性物质中的应用进行归纳与总结。结果与结论微透析与液相色谱-质谱联用作为一种新型的分析技术,具有快速简便、干扰少、前处理简单等优点。此项技术在体内药物分析中得到了迅速推广和应用,特别在药代动力学研究中显示出其独特的优势,具有十分广阔的应用前景     

液-质联用中大气压电离接口技术及其在药物分析中的应用

目的：介绍液相色谱-质谱联用技术（LC-MS）在药物分析中的应用。方法：通过介绍液相色谱-质谱技术原理，引入大气压电离接口技术，并综述了在药物分析中的应用。结果：液相色谱-质谱技术对药物的杂质检查与降解产物、药动学、药物代谢产物的分析和鉴定、生物大分子以及药物开发得到了广泛应用。结论：大气压电离接口技术，扩大了液相色谱-质谱联用技术的应用范围，促进了药物分析学科的发展。     

液相色谱——质谱联用技术及其在天然药物分析中的应用

目的　介绍近年来液相色谱—质谱联用技术的研究进展及其在天然药物分析中的应用。方法　主要介绍液相色谱—质谱(LC -MS)接口技术中API技术的研究进展及液相色谱 -电喷雾离子化质谱(LC -ESI -MS)。液相色谱 -大气压化学离子化质谱(LC -APCI -MS)等技术在天然药物分析中的应用。结果及结论　液相色谱 -质谱在接口技术方面取得了很大进展,且随着该技术的不断完善液质联用技术在天然药物分析中占据越来越重要的地位     

色谱-质谱联用技术用于遗传毒性杂质检测的研究进展

遗传毒性杂质种类繁多且通常痕量存在于药物中,而色谱-质谱联用技术具有相对更高的灵敏度和选择性,极适用于分析药物中的遗传毒性杂质。主要介绍了如何根据遗传毒性杂质的极性、挥发性、热不稳定性等理化性质建立合适的色谱-质谱联用技术,并综述了气相色谱、液相色谱、超高液相色谱、亲水性相互作用色谱、超临界流体色谱、毛细管电泳色谱6种色谱技术与质谱联用在遗传毒性杂质（如亚硝胺类、磺酸酯类、卤代烷烃类等）检测中的研究进展,从而为建立科学合理的遗传毒性杂质检测方法提供参考。     

液相色谱-质谱联用技术在中药方剂现代研究中的应用进展

液相色谱与质谱联用技术(LC-MS)将液相色谱的高分离效能与质谱的结构鉴定功能结合起来,已逐渐成为方剂现代研究的强有力手段.本文从液相色谱与质谱联用技术在各类型化合物裂解规律研究、方剂中效应成分快速定性定量分析、方剂配伍规律研究、方剂效应物质的体内代谢研究等方面的应用进展进行了综述,并对该技术目前在方剂研究中存在的问题及应用前景进行展望.     

色谱联用技术在中药研究领域的应用

中药现代化离不开现代、高效的分离、分析技术。现代分析技术的发展，尤其是色谱联用技术的出现加快了中药研发的步伐。该技术具有所需样品量少、速度快等特点，且可得到更多信息。目前，正处于快速发展阶段并广泛应用的色谱联用技术包括气相色谱-质谱联用（GC—MS）、液相色谱质谱联用（LC—MS）、高效液相-核磁共振仪联用（HPLCNMR）、毛细管电泳-核磁共振仪联用（CE—NMR）、液相色谱-质谱／质谱联用（LC一／MS／MS）、液相色谱-核磁-质谱联用（LC—NMR—MS）、毛细管电泳-质谱联用（CEMS）等，本就其在中药研究领域的应用作一简要综述。     

液-质联用在体内药物分析中的应用

目的:综述液相色谱-串联质谱联用在体内药物分析中的应用,为进一步扩大应用提供参考。方法:检索国内2008-2009年相关文献,进行分析、整理和归纳。结果:液相色谱-串联质谱联用集液相色谱的高分离效能与质谱的高鉴定性能于一体,对研究对象有足够的灵敏度、选择性,分析快速且方便,在药学研究方面的应用日益广泛。结论:液相色谱-串联质谱联用是目前最重要的分离分析方法之一,将在未来几年不断发展且在体内药物分析中发挥越来越重要的作用。     

Reducing the development of antibiotic resistance in critical care units

Bacteria becoming resistant to an increasing number of antibiotic classes are a major problem at hospitals including critical care units worldwide. Awareness of this problem and the need to prevent the development of antibiotic resistance are very important, especially since very few new antibiotics will become available in the near future. This article gives an overview of the mechanisms of antibacterial resistance and actual resistance data worldwide of the most prevalent Gram positive (MRSA, VISA/VRSE and VRE) and Gram negative bacteria (Pseudomonas aeruginosa, Acinetobacter spp., ESBL producing Enterobacteriaceae and Stenotrophomonas maltophilia). Furthermore, strategies to reduce antibiotic resistance are reviewed. Most important is institution of infection control policies including guidelines on surveillance, isolation of colonized patients and contact precautions, hand hygiene, decolonization measures and environmental decontamination. Antimicrobial stewardship, or striking the balance between an optimal antibiotic treatment for a patient and a minimal risk of development of antibiotic resistance, is another important strategy. Finally, optimizing of antibiotic dosage regimens and thus avoiding underdosage is essential to avoid selection of the most resistant subpopulation of bacteria during antibiotic treatment. Intensive care units with knowledge of local epidemiology of resistance, an effective infection control program and antimicrobial stewardship policy tailored to their specific needs, and using optimal antibiotic dosing regimens have both locally decreased the risk of an outbreak with multi-resistant bacteria, and maybe even more important help to reduce the development of antibiotic resistance.     

鲍曼不动杆菌抗生素主动外排泵转运系统与外排泵抑制剂

鲍曼不动杆菌(Acinetobacter baumannii)是医院内感染的重要病原菌,其耐药率呈现上升的趋势。该菌存在多种耐药机制,其中药物主动外排转运系统或外排泵介导的抗菌药物主动外排与多重耐药(multi-dmg resistance,MDR)密切相关,是近年来研究细菌多重耐药机制的重点。外排泵抑制剂(efflux pump inhibitors,EPIs)的研发有助于克服细菌主动外排机制导致的多重耐药性,为逆转细菌的多重耐药提供了一条新思路。本文就近年来鲍曼不动杆菌的药物主动外排转运系统与外排泵抑制剂的研究进展进行综述。     

The use of quorum-sensing blockers as therapeutic agents for the control of biofilm-associated infections

The development of novel antimicrobial compounds is required to treat the growing number of infections where antibiotic resistance is a serious threat, especially in situations where biofilms are involved. Antibiotic resistance is the result of two factors: first, through the development of specific antibiotic resistance, due to either mutation or the acquisition of antibiotic resistance genes; and second, by the innate tolerance of bacterial biofilms. Bacterial control, through the inhibition of bacterial cell-cell communication systems which are involved in the regulation of virulence factor production, host colonization, and biofilm formation, is discussed in this review. Specifically, this review presents current studies on the development of quorum-sensing inhibitors for the control of bacterial infections.     

Nano-technology for targeted drug delivery to combat antibiotic resistance

Several microbes have evolved clinically significant resistance against almost every available antibiotic. Yet the development of new classes of antibiotics has lagged far behind our growing need. Frequent and suboptimal use of antibiotics particularly in developing countries aggravated the problem by increasing the rate of resistance. Therefore, developing new and multidimensional strategies to combat microbial infections is warranted. These include i) modification of existing antibiotics, ii) searching new and novel antibiotics, iii) development and improvement of antibiotics carrier system to reduce amount and frequency of antibiotic doses, iv) development of targeted antibiotic delivery systems. Here, the authors discuss trends and development of nano-materials and alternative antimicrobials to solve the problem of antibiotic resistance.     

国内外抗耐药复方抗生素研发的现状及开发策略

细菌耐药导致β-内酰胺类抗生素临床使用严重受限,β-内酰胺酶抑制剂与该类抗生素合用有效解决了这一难题。近年来,欧美在新复方抗生素研发方面发展迅速,尤其是近两年FDA先后快速批准了两个新的β-内酰胺类抗生素/β-内酰胺酶抑制剂复方抗生素,分别为ceftolozane/三唑巴坦(商品名:zerbaxa)和头孢他啶/阿维巴坦(商品名:avycaz),很大程度的缓解了目前耐药菌无药可用的局面。我国药企基于已有的β-内酰胺类抗生素和β-内酰胺酶抑制剂进行较多探索研究,目前已有多家药企在复方抗生素的开发中投入了大量研究。本文阐述了国内外复方抗生素研发情况、政策法规对研发内容的要求、政府对抗耐药菌抗生素研发的鼓励政策,分析国内复方抗生素研发的不足并提出开发建议,为国内合理开发该类抗生素提供参考。     

Residual quantities of streptomycin sulfate in haemolymph and tissue of Heliothis virescens reared on treated diet

The study showed that streptomycin sulfate was present in both tissue and blood of insects fed with the antibiotic-treated diet. Changes from larval to pupal to adult stages were accompanied by decreases in antibiotic concentration. During transformation from pupa to adult most of the antibiotic was discarded with the meconium. Eggs from adults reared from larvae fed on the antibiotic-treated diet were free of streptomycin. The antibiotic did not adversely affect insect development.     

Past,Present, and Future of Antibacterial Economics: Increasing Bacterial Resistance,Limited Antibiotic Pipeline,and Societal Implications

Growing antimicrobial resistance and a dwindling antibiotic pipeline have resulted in an emerging postantibiotic era, as patients are now dying from bacterial infections that were once treatable. The fast‐paced “Golden Age” of antibiotic development that started in the 1940s has lost momentum; from the 1980s to the early 2000s, there was a 90% decline in the approval of new antibiotics as well as the discovery of few new novel classes. Many companies have shifted away from development due to scientific, regulatory, and economic hurdles that proved antibiotic development to be less attractive compared with more lucrative therapeutic areas. National and global efforts are focusing attention toward potential solutions for reinvigorating the antibiotic pipeline and include “push” incentives such as public–private partnerships and “pull” incentives such as reimbursement reform and market exclusivity. Hybrid models of incentives, global coordination among stakeholders, and the appropriate balance of antibiotic pricing, volume of drug used, and proper antimicrobial stewardship are key to maximizing efforts toward drug development to ensure access to patients in need of these therapies.     

Coping with antibiotic resistance: the impending crisis

Global changes in antibiotic production and use patterns, in synergy with climate change, suggest that antibiotic resistance will only increase. When combined with the crisis in new drug development, antibiotic stewardship becomes ever more important in order to preserve the activity of these unique drugs.     

Cost and quality considerations in antibiotic formulary management

Numerous factors are considered in the design of an antibiotic formulary, consisting primarily of indicators of clinical efficacy and safety, as well as economic viability. Similarly, there are many potential strategies for subsequent antibiotic formulary management ranging from global educational efforts to comprehensive required antibiotic justification programs. Antibiotic formulary management programs should be tailored to individual institutions and utilize a multidisciplinary approach where possible. The primary outcome goals of such programs are generally controlled antibiotic costs, optimized clinical efficacy, minimization of adverse events, and reduced microbial resistance development, although quantification of program impact on these parameters continues to be a challenge.     

44th Interscience Conference on Antimicrobial Agents and Chemotherapy: an update on new antibiotics, novel non-antibacterial treatment modalities and critical issues in antibiotic resistance

The recent 44th annual Interscience Conference on Antimicrobial Agents and Chemotherapy provided a snapshot of the antibiotics most advanced in clinical development. New antibiotic discovery programs and novel efforts in the field of non-antibiotic treatment modalities were also presented. Some of the most pressing issues in antibiotic resistance were discussed at this meeting.