“中国药典2005年版抗生素品种色谱柱推荐系统”的建立与应用

目的：建立“中国药典2005年版抗生素品种色谱柱推荐系统”（简称“色谱柱推荐系统”）。方法：中国药品生物制品检定所（简称中检所）选择抗生素品种，色谱柱公司筛选色谱柱并优化色谱方法，中检所最终复核，对色谱柱的适用性进行了研究，并将相关实验结果以网络型数据库的方式公布。结果：在网址（http：／／www．antibiotic．cn／columnt．htm）建立了“中国药典2005年版抗生素品种色谱柱推荐系统”。结论：收载了多个色谱柱公司提供的色谱图，为使用单位选择色谱柱提供了方便，拓宽了应用范围。     

乙酰螺旋霉素组分分析中色谱柱的理性选择方法探讨(英文)

乙酰螺旋霉素为碱性的多组分抗生素,是以螺旋霉素为起始原料的半合成抗生素。乙酰螺旋霉素原料药中除了单-乙酰螺旋霉素Ⅱ和Ⅲ、双-乙酰螺旋霉素Ⅱ和Ⅲ四种主成分外,还能检出70多种小组分,这些小组分的结构与主成分相似或为主成分的同分异构体,故将乙酰螺旋霉素的各组分基线分离很具挑战性;在实际工作中还发现,采用不同品牌的C_(18)柱所得的乙酰螺旋霉素组分测定结果有时差异较大,有必要采用科学的方式理性挑选适宜的色谱柱进行其组分测定。本文利用国际上较有影响力的鲁汶大学所建的色谱柱分类系统数据库,以文献报道的CAPCELL PAK MG C_(18)柱(250 mm×4.6 mm,5μm)作为参比柱,选择了3组选择性不同的色谱柱,并按照中国药典2010版乙酰螺旋霉素各论项下的方法考察了这3组色谱柱的实际分离情况。与参比柱的结果相比,F<2组的分离效果最好,F>6组的分离效果最差,而26组色谱柱(F≥9.9)的绝对差异则超过2.5%,甚至高达8.2%,...     

头孢菌素类抗生素中高分子杂质测定实验技术的改进

在头孢类抗生素高分子杂质含量的测定中采用柱切换技术 ,使检测时间从 3～ 4h/批减少到0 .5h/批 ;在色谱柱中添加脱脂棉滤层 ,使色谱柱寿命延长 2～ 3倍。方法简单、高效、可靠。     

联合使用反相液相色谱,柱切换以及两性离子交换-反相亲水性相互作用混合模式色谱-质谱法分析抗生素中的杂质

建立并优化了一种二维柱切换、高效液相色谱-质谱联用（LC-MS/MS）系统,用于分析抗生素及其有关物质。在一维色谱中,采用两性离子交换-反相亲水性相互作用（ZIC-RP-HILIC）混合模式色谱柱对目标杂质进行分离,并采用液质联用技术（LC-MS/MS）进行检测。在二维色谱中,采用常规的反相LC色谱柱对供试品及其杂质进行分析。ZIC-RP-HILIC混合模式色谱系统的流动相为一种适用于LC-MS/MS的可挥发性缓冲盐,能够提高杂质的离子化效率,便于对目标杂质进行结构解析。直接采用ZIC-RP-HILIC-MS系统,对使用离子对反相色谱分离的抗生素杂质进行定性分析。ZIC-RP-HILIC混合模式色谱与反相LC色谱系统之间的正交性,进一步保证了杂质检测的全面性。此方法的优势体现在对青霉素V钾,苯唑青霉素钠、头孢曲松钠的杂质分析中。另外,该方法便于进行抗生素的杂质谱分析,并可用于其它药物的杂质分析。     

药物分析中C18色谱柱的差异与选择

在药物分析中高效液相色谱法用得非常普遍,而色谱柱的选择直接影响实验结果与药物的质量控制。不同C18色谱柱的保留行为千差万别,选择适宜的色谱柱对分析样品至关重要。以C18色谱柱的内部化学键合相为切入点,介绍C18色谱柱的差异,并综述在不同的pH环境、流动相极性、药物极性等条件下以及根据色谱柱的分类系统选择合适的键合相,为如何正确快速的选择C18色谱柱提供参考。     

土茯苓含量测定分离度和理论板数的调整

目的为准确测定土茯苓中落新妇苷的含量,探索提高理论板数、分离度的方法提供依据。方法采用不同品牌色谱柱、调节流速、进样量、色谱柱温度,分别测定落新妇苷的保留时间、分离度、理论板数。结果色谱柱、流速、进样量、色谱柱温度等的不同均可影响高效液相色谱的保留时间、分离度、理论板数。结论在高效液相色谱测定时,可通过采用不同品牌的色谱柱,调整流速、进样量、色谱柱温度等方法改善液相色谱的分离度、理论板数。     

对抗生素生产中废溶媒定性分析方法的探讨

目的:对抗生素生产中废溶媒进行定性分析。方法:毛细管气相色谱法,色谱柱:HP—1701熔融石英色谱柱(30m×0.25mm×0.25μm)。结果:通过实验条件的选择,得到一个稳定、快速的定性分析的方法。结论:此法可用于连续分析。     

埃索美拉唑钠有关物质中奥美拉唑磺酰化物的HPLC定位分析

目的 探讨在不同HPLC色谱条件对主成分埃索美拉唑钠与其主要杂质奥美拉唑磺酰化物色谱峰的影响.方法 采用高效液相色谱法,色谱柱有Welch Materials Xtimate-C8柱、Phenomenex b-sil-C8柱、Zorbax Eclipse XDB-C8柱、Kromasil-C8柱、Spherisorb-C8柱、Welch Materials Welchrom-C18柱;流动相为0.01mol/L磷酸氢二钠(磷酸调节pH至7.6)-乙腈(67:33);流速1mL/min;检测波长280nm;进样量20μL.结果 不同品牌和规格的色谱柱可对埃索美拉唑钠和奥美拉唑磺酰化物的色谱峰产生明显的影响;而其他色谱条件则基本没有影响.结论 影响埃索美拉唑钠与其主要杂质奥美拉唑磺酰化物色谱峰的主要因素为色谱柱.     

对桑叶配方颗粒芦丁含量测定中色谱柱使用的建议

目的：建议在桑叶配方颗粒芦丁含量测定项使用极性改性C18色谱柱。方法：分别使用多款不同规格的十八烷基键合硅胶（C18）固定相色谱柱，考察桑叶配方颗粒中芦丁的分离情况。结果：使用极性改性C18色谱柱能有效分离芦丁及其共存成分。结论：色谱柱是影响含量测定结果准确性的关键因素，在实际检测过程中应充分考虑不同色谱柱之间的差异，降低因色谱柱选择性差异导致检测结果不准确的风险。     

色谱柱参数对盐酸四环素有关物质HPLC分析的影响研究

摘要：目的 分析色谱柱参数对盐酸四环素有关物质HPLC分析的影响，筛选影响关键杂质分离度以及理论塔板数的主要 柱参数。方法 针对《中国药典》2020版中盐酸四环素有关物质检查的色谱条件，使用多个品牌不同型号的色谱柱进行色谱分 析，使用SPSS软件进行模型回归，得到柱参数与目标因子分离度及理论塔板数的回归方程，并用实测值进行验证。结果 色谱 柱参数C是影响杂质4-差向四环素和土霉素分离度(R12)的重要参数，利用柱参数C可快速预测不同色谱柱的相似度，进而筛选 适宜四环素分析的色谱柱；探讨了金霉素理论塔板数(R5N)与柱参数之间的关系，其中参数B2对R5N影响较大。结论 建立柱参 数与色谱分析目标因子之间的联系，为盐酸四环素有关物质测定选择合适的色谱柱提供便利与指导。     

Reverse phase high speed liquid chromatography of antibiotics. II. Use of high efficiency small particle columns

Improved methods for the separation and quantitation of cephalosporins, penicillins, tetracyclines and several miscellaneous antibiotics by reverse phase high speed liquid chromatography are presented. The methods have been improved significantly by the substitution of high efficiency, small particle (approximately 10 micrometer reverse phase columns in place of the previously used medium efficiency, pellicular columns. The conditions and procedures described here illustrate that considerable improvements in separation and sensitivity of detection of antibiotics are achieved. Pure compounds, complex mixtures of antibiotics in a variety of dosage forms and fermentation broths are routinely analyzed by the described procedures.     

Isolation and characterization of A41030, a complex of novel glycopeptide antibiotics. Application of the Michel-Miller high performance low pressure liquid chromatography system

A new antibiotic complex, designated A41030, has been isolated from the fermentation broth of Streptomyces virginiae. Factors A, B, C, D, E, F and G were separated by an efficient preparative high performance low pressure liquid chromatography system. The apparatus offers economic reversed phase separations on glass columns. The A41030 factors are members of the general class of glycopeptide antibiotics and are active in vitro and in vivo vs. Gram-positive bacteria.     

High-performance liquid chromatography of anthracycline antibiotics with electrochemical detection. Application to the clinical pharmacokinetics of 4'-deoxydoxorubicin

The high-performance liquid chromatography with electrochemical detection (HPLC-EC) of six anthracycline antibiotics is described. All the compounds of interest may be analysed using a reversed-phase column (ODS Hypersil or Zorbax ODS) and a mobile phase consisting of acetonitrile-isopropanol-0.1 M phosphate buffer (pH 4.5). The use of short columns (7.5 cm) allowed short analysis times and improved sensitivity, such that detection limits of between 1 and 2 ng ml(-1) could be achieved. Sample preparation involved an alkaline extraction into chloroform, followed by a back extraction into acid solution. Final clean-up of the samples is achieved by shaking the final acidic extract with an organic solvent. The precision of the assay for the compounds studied ranges between 1.22 and 6.46% and the accuracy ranges between 94.5 and 106.0%. The analytical methodology developed is applied to the clinical pharmacokinetics of 4'-deoxydoxorubicin. The correlation between plasma levels found by HPLC-EC and those found by HPLC with fluorescence detection is excellent (r(2) = 0.990).     

Selective depletion of neuropathy-related antibodies from human serum by monolithic affinity columns containing ganglioside mimics

Monolithic columns containing ganglioside GM2 and GM3 mimics were prepared for selective removal of serum anti-ganglioside antibodies from patients with acute and chronic immune-mediated neuropathies. ELISA results demonstrated that anti-GM2 IgM antibodies in human sera and a mouse monoclonal anti-GM2 antibody were specifically and selectively adsorbed by monolithic GM2 mimic columns and not by blank monolithic columns or monolithic GM3 mimic columns. In control studies, serum antibodies against the ganglioside GQ1b from another neuropathy patient were not depleted by monolithic GM2 mimic columns. Fluorescence microscopy with FITC-conjugated anti-human immunoglobulin antibodies showed that the immobilized ganglioside mimics were evenly distributed along the column. The columns were able to capture ～95% of the anti-GM2 antibodies of patients after only 2 min of incubation. A monolithic column of 4.4 μL can deplete 28.2 μL of undiluted serum. These columns are potential diagnostic and therapeutic tools for neuropathies related to anti-ganglioside antibodies.     

黄曲霉毒素免疫亲和柱重复利用的探讨

目的考察中药材类别和亲和柱处理方法对黄曲霉毒素免疫亲和柱重复利用的影响,探讨亲和柱重复利用的可能性。方法通过在不同中药材中加入黄曲霉毒素对照品,经免疫亲和柱净化一HPLC-柱后光衍生分析,考察亲和柱重复利用后的回收率;考察不同的亲和柱处理方法对回收率的影响。结果中药材类别对免疫亲和柱重复利用的影响差异很大,部分种子类中药材使用后亲和柱重复利用3次回收率无明显变化,部分根茎类使用后,亲和柱回收率降低明显,特别是G：更易受影响。亲和柱处理时有机溶剂,空气暴露和复性时间均可影响柱子重复利用。结论中药材类别和处理方法对黄曲霉毒素免疫亲和柱的重复利用均有显著影响。     

Evaluation of analytical methods: Liquid chromatography of cefalexin

A comparative study of three isocratic liquid Chromatographic methods for the analysis of cefalexin is described. Two methods, taken from the European Pharmacopoeia and the US Pharmacopeia, use classical alkyl bonded phases (C₁₈) as the stationary phase. The third method uses poly(styrene-divinylbenzene). Poor reproducibility of the selectivity towards cefalexin and its related substances was observed for the C₁₈ columns. In both C₁₈ methods, none of the columns was able to separate all the potential related substances from cefalexin under the prescribed LC conditions. The copolymer columns on the other hand showed good selectivity, independent of the origin or age of the columns. Four bulk samples of cefalexin were analysed by these three methods and the results were compared. Although the selectivity of polymer columns was better, for the samples examined no significant differences were observed for the assay results obtained with the three methods.     

Demonstration of the compatibility of narrow-bore packed column high-performance liquid chromatography with conventional detection systems

A number of commercially available high-performance liquid chromatography detectors fitted with conventionally sized flow cells (4.5 to 14 microliters) have been evaluated for use for narrow-bore (1-3 mm i.d.) packed columns. Contrary to the popular misconception, small flow cell volume (and consequently short path length) does not appear to be a prerequisite for successful use of narrow-bore columns. The 1 mm i.d. columns when used with certain detectors gave up to a 17-fold increase in sensitivity, compared with conventional 4.6 mm i.d. columns. This work, which was carried out using conventional injection volumes (50 microliters), shows that narrow-bore HPLC columns can be used in most laboratories to significant advantage without costly conversion of existing equipment.     

基于医疗联合体的抗菌药物新型管理模式对基层医院儿科抗菌药物合理应用干预研究

目的：探讨以医疗联合体为基础的抗菌药物新型管理模式对基层医院儿科抗菌药物合理应用的干预效果。方法：随机抽取扬州大学附属医院医疗联合体基层医院成员单位抗菌药物合理应用干预前后门诊儿科急性呼吸道感染诊疗日志各200份,统计抗菌药物使用率、联合应用率、抗菌药物人均费用、标本送检率、抗菌药物选择及疗程符合标准指南的比例等,分析干预前后抗菌药物合理应用情况,评价基于医疗联合体的抗菌药物新型管理模式对基层医院儿科抗菌药物合理应用的干预效果。结果：干预后,基层医院儿科急性呼吸道感染抗菌药物使用率、抗菌药物联合应用率、抗菌药物人均费用均降低（P<0.05）;标本送检率、抗菌药物选择及疗程符合标准指南的比例升高（P<0.05）。结论：以区域医疗联合体为平台的抗菌药物新型管理模式,能够指导和干预基层医院儿科抗菌药物合理应用,有效提高基层医院儿科抗菌药物合理应用水平。     

上海市松江区中心医院2010--2012年住院药房抗生素使用情况分析

目的了解上海市松江区中心医院住院药房抗生素的使用情况,为临床合理用药提供参考。方法统计2010---2012年住院药房抗生素的消耗金额、用药总剂量、限定日剂量（DDD）、用药天数、用药频率（DDDS）、日均费用（DDC）、药物利用指数（DUI）以及抗生素使用率、抗生素使用强度（AUD）等,分析临床应用情况。结果3年来上海市松江区中心医院抗生素使用率和使用强度都超过了卫生部的相关标准,但呈现下降趋势。结论住院药房对抗生素的用药基本合理,但个别药物DUI〉1,存在不合理使用情况,应进一步加强对抗生素使用的监督管理,防止少数抗生素的滥用。     

我院抗菌药使用情况回顾性分析

随机抽取我院 ９７年１～６月份出院病历 １５８份，其中 １２２份（７７．２％）使用了抗菌药，本文仅对此１２２份使用抗菌药情况进行综合分析。我们发现：有６８例病人（５５．７％）抗菌药使用不合理；有８１例为预防性使用抗菌药，治疗用药仅３５例，防治兼顾有６例；有７例发生医院感染；住院期间只使用过１种抗菌药的有４２例，用过２种有３２例，２种以上有４８例，最多为７种；共用抗菌药４５种，１９６疗程，其中１联１１１疗程，２联５９疗程，３联２０疗程，３联以上６疗程，最多１例为６联，共计用药２００７ｄ，平均每疗程１０．２ｄ，每例平均用药１６．５ｄ。本文还讨论了抗菌药滥用与院内感染的关系，以及目前预防用药存在的问题，并对如何合理使用抗菌药提出了几点建议。