HPLC-加校正因子的主成分自身对照法测定注射用头孢孟多酯钠的有关物质

目的：采用自建的方法测定注射用头孢孟多酯钠中杂质A、杂质C、杂质D和杂质E相对于头孢孟多酯的校正因子,以确定最佳的定量方式,提高有关物质测定结果的准确度。方法：用十八烷基硅烷键合硅胶为填充剂,以0.05 mol·L-1甲酸铵溶液（用甲酸调至pH值至4.5）为流动相A,乙腈为流动相B,线性梯度洗脱,柱温30℃,检测波长254 nm。分别采用不同品牌的高效液相色谱仪及不同规格和来源的色谱柱对杂质A、杂质C、杂质D和杂质E的校正因子进行测定,并将测定结果和主成分自身对照法及外标法进行对比。结果：各色谱系统中主成分头孢孟多酯与相邻杂质及各已知杂质之间分离均良好,头孢孟多酯、杂质A、杂质C、杂质D和杂质E在0.05~2.5μg·mL-1浓度范围内线性关系均良好（r>0.999）,杂质A、杂质C、杂质D和杂质E的校正因子分别为1.10,1.12,0.59和1.17,杂质D和杂质E的定量方式以加校正因子的主成分自身对照法为宜。6批样品杂质A结果均约为0.2%,杂质C均约为0.1%,杂质D均约为0.02%,杂质E分别为0.06%、0.04%、0.05%、0.05%、0.08%和0.08%,其它单个最大杂质均约为0.1%,校正后总杂质分别为0.9%、0.8%、0.9%、0.8%、0.8%和0.8%。结论：通过对各已知杂质校正因子的测定,无需持续提供杂质对照品,即可准确测定注射用头孢孟多酯钠的有关物质,本方法操作简单,结果准确可靠,可为含类似结构的抗生素类药物定量方法的改进提供参考。     

注射用头孢孟多酯钠与木糖醇注射液配伍稳定性考察

目的 观察注射用头孢孟多酯钠与木糖醇注射液配伍的稳定性.方法 室温(25℃)下,将注射用头孢孟多酯钠分别与5%和10%木糖醇注射液配伍,于0、1、2、4、6、8、24 h取样,采用紫外分光光度法测定主药吸光度值的变化以确定相对含量变化,同时测定pH值.结果 注射用头孢孟多酯钠与5%和10%木糖醇注射液在室温(25℃)下配伍,0～8 h内其外观、pH值及含量无明显变化.结论 本试验提示头孢孟多酯钠与木糖醇注射液配伍较为稳定,其试验结果可供临床配伍使用参考.     

注射用头孢孟多酯钠与注射用奥美拉唑钠序贯静滴的稳定性研究

目的：研究注射用头孢孟多酯钠与注射用奥美拉唑钠序贯静滴的配伍稳定性。方法：参考临床常用质量浓度,配制头孢孟多酯钠与5%葡萄糖注射液配伍溶液,再取该配伍溶液分别与不同体积的奥美拉唑钠溶液配伍。于0,0.5,1,2,3,4,5,6 h观察各配伍液的外观性状变化,测定pH值和不溶性微粒数,并采用HPLC法测定各配伍液头孢孟多酯钠的相对百分含量。结果：头孢孟多酯钠与5%葡萄糖注射液的配伍液在6 h 内外观无明显变化,与不同体积奥美拉唑钠配伍的配伍液随时间延长出现不同颜色的浑浊,在6 h内各配伍液中不溶性微粒数均符合规定,头孢孟多酯钠的相对百分含量略有下降。结论：在临床上,若注射用头孢孟多酯钠与注射用奥美拉唑钠静滴联用时,最好在两者之间先用0.9%氯化钠注射液清洗输液管道,完毕后再输注另一种药物,或者不将两者连续使用。     

注射用头孢孟多酯钠中碳酸钠用酸碱滴定法测定的可行性研究

目的：对美国药典30版注射用头孢孟多酯和英国药典2005年版收载的头孢孟多酯钠中碳酸钠的含量测定方法的可行性进行考证。方法：采用酸碱滴定法和离子色谱法。结果：注射用头孢孟多酯钠的离子色谱检测中检出碳酸根离子和甲酸根离子，并且随着检测溶液形成时间的增加水解产生的甲酸也增加。结论：注射用头孢孟多酯钠中的碳酸钠被头孢孟多酯钠水解产生的甲酸中和，不能用酸碱滴定法对头孢孟多酯钠中的碳酸钠定量。因此，美国药典和英国药典在注射用头孢孟多酯和头孢孟多酯钠标准中收载的方法并不可行。     

注射用头孢孟多酯钠在4种常用液体中的稳定性考察

目的考察注射用头孢孟多酯钠在25℃下与0．9％氯化钠注射液、5％葡萄糖注射液、10％葡萄糖注射液和5％葡萄糖氯化钠注射液4种常用输液液体配伍的稳定性。方法将注射用头孢孟多酯钠与输液配伍,采用高效液相色谱法测定头孢孟多酯钠的含量变化,并考察配伍液的外观和pH变化。结果注射用头孢孟多酯钠与0．9％氯化钠及5％葡萄糖氯化钠在室温下（25％）配伍,0～8h内其外观、pH值及含量无明显变化。而与5％葡萄糖注射液、10％葡萄糖注射液配伍稳定性欠佳。结论注射用头孢孟多酯钠与输液配伍时应选择0．9％氯化钠注射液或5％葡萄糖氯化钠注射液,不宜与5％葡萄糖注射液和10％葡萄糖注射液配伍。     

HPLC法测定注射用头孢孟多酯钠中有关物质

目的 建立HPLC对注射用头孢孟多酯钠中有关物质进行测定的方法。方法 菲罗门Luna C₁₈(2)色谱柱(250 mm×4.6 mm,5μm),流动相为1%三乙胺溶液(用磷酸调节pH值至2.5)-乙腈(76:24),体积流量为1.5 mL/min,检测波长为254 nm,柱温为40℃,进样量为20μL。采用杂质对照品法外标法计算杂质D,采用加校正因子的主成分自身对照法计算杂质A、E、C。结果 杂质D为主要降解产物,定量限为0.01%,在0.02~0.20μg与峰面积线性关系良好。杂质A、E、C的校正因子分别为1.14、1.25、1.14,检测限分别为0.004%、0.02%、0.04%。结论 杂质D、A、E、C作为特定杂质应订入质量标准,可以更好地控制注射用头孢孟多酯钠中有关物质。     

HPLC-DAD考察头孢孟多酯钠与卡络磺钠在5%葡萄糖注射液和0.9%氯化钠注射液中的配伍稳定性

目的考察室温(25℃)下,注射用头孢孟多酯钠与注射用卡络磺钠分别在5%葡萄糖注射液和0.9%氯化钠注射液中的配伍稳定性。方法采用反相高效液相色谱法-二极管阵列检测器分别测定0～6 h内配伍液中头孢孟多酯钠和卡络磺钠的含量变化,同时观察配伍溶液的外观和测定其pH值。结果在室温(25℃)下、6 h内,配伍液外观无明显变化,但pH值和含量均变化明显。结论在室温(25℃)下、6 h内,注射用头孢孟多酯钠与注射用卡络磺钠在5%葡萄糖注射液和0.9%氯化钠注射液中配伍均不稳定。     

注射用头孢孟多酯钠与常用输液的配伍试验

目的：观察注射用头孢孟多酯钠与常用三种输液配伍的稳定性。方法：将注射用头孢孟多酯钠与常用输液配伍,采用紫外分光光度法测定其吸光度值的变化以确定相对含量变化,同时测定pH值。结果：注射用头孢孟多酯钠与0．9％氯化钠及5％葡萄糖氯化钠在室温下（25℃）配伍,0～8h内其外观、pH值及含量无明显变化。而与5％葡萄糖在室温下（25℃）配伍稳定性欠佳。结论：本试验提示此药物在氯化钠存在条件下较为稳定,其试验结果可供临床配伍使用参考。     

凝胶色谱法测定注射用头孢孟多酯钠中高分子聚合物的含量

目的 建立以凝胶色谱法测定注射用头孢孟多酯钠中的高分子聚合物的方法.方法 采用凝胶色谱柱,色谱柱为Sephadex G-10(15.0mm×300mm),流动相A为pH 7.0的0.01mol·L-1磷酸盐缓冲液,流动相B为水,流速为每分钟1.4mL,检测波长为254nm,进样量为200μL.结果 验证了头孢孟多酯钠高...     

36例头孢孟多酯钠不良反应的文献分析

目的 了解头孢孟多酯钠不良反应(ADR)的情况,促进临床合理用药.方法 采用文献计量学方法,收集头孢孟多酯钠公开报道的全部ADR,对因果关系明确的36例头孢孟多酯钠ADR病例进行总结性分析.结果 头孢孟多酯钠所致ADR以10岁以下儿童和60岁以上老年人居多,共27例,占75％.其中,头孢孟多酯钠致皮肤及其附件损害6例;因饮酒导致双硫仑样反应9例;泌尿系统损害致血尿3例;中枢及外周神经系统损害致精神异常3例;全身性损害共15例.结论 使用头孢孟多酯钠时应重点关注儿童和老年人群用药安全;加强医护患对易引起双硫仑样反应的抗菌药物的禁酒宣教及认识,以减少或杜绝双硫仑样反应的发生;头孢孟多酯钠引起的中枢神经系统及全身性损害等严重不良应不容忽视.     

Electrochemical analysis of the cephalosporin cefamandole nafate.

The polarographic assays for cefamandole sodium and its formyl ester, cefamandole nafate, are described. Controlled potential coulometry is used as an absolute method for the assignment of purity of these compounds without the need for a reference material. The precision, accuracy, and selectivity of these assays were better than for the microbiological autoturbidimetric and automated iodometric assays. NMR, TLC, GC, and polarography are used to detect and quantitate likely impurities and degradation products.     

头孢孟多酯钠致精神异常

1例76岁男性患者,因腰椎间盘髓核摘除术术后,静脉滴注头孢孟多酯钠1g 溶于0.9 %氯化钠注射液250 mL 预防感染.滴注20 min 后,患者出现意识模糊、燥动不安、对答不切题.立即停药,给予消炎、镇静等处理,4h 后患者精神异常症状消失.继续给予止血、制酸治疗,患者未有不适症状出现.     

踝关节骨折临床路径中抗菌药物应用的优化

目的:筛选踝关节骨折临床路径中预防性应用抗菌药物的合理化用药方案。方法:回顾性分析我院2008-2010年204例踝关节骨折围手术期预防性应用抗菌药物的情况,筛选出磺苄西林钠、头孢呋辛钠、头孢孟多酯钠和头孢美唑钠4种抗菌药物进行成本-效果分析。结果:204例患者预防性应用抗菌药物使用率100%,术前0.5～2h用药44例(21.57%),平均用药时间(6.03±2.51)d。磺苄西林钠、头孢呋辛钠、头孢孟多酯钠和头孢美唑钠的成本分别为1987.20、892.56、3644.28、1241.28元,有效率分别为71.43%、87.50%、88.46%、97.50%,成本-效果比分别为2782.02、1020.07、4119.69、1273.11,头孢孟多酯钠和头孢美唑钠相对于头孢呋辛钠的增量成本-效果比分别是286637.50和3487.20。结论:实施踝关节骨折临床路径需要优化抗菌药物的预防性应用,头孢呋辛钠可作为较佳用药方案。     

Kinetics of cefamandole nafate degradation in solid phase

The influence of temperature and relative humidity (RH) on the stability of cefamandole (CM) nafate sodium in the solid phase was investigated. Changes in the concentration of cefemandole nafate sodium were recorded using HPLC with UV detection. The method was validated for the following parameters: selectivity, linearity, precision, limit of detection and sensitivity. It showed good linearity (r=0.9996) in the range 0.4 x 10(-4)-5.6 x 10(-4) g ml(-1) using a LiChrospher RP-18 column and as mobile phase acetonitryle-triethylamine (10% v/v, adjusted to pH 2.5 with phosphoric acid (84%) and diluted with water) (35:65). The degradation of CM occurring at 0% RH of the ambient air and at air humidity RH>50% is a first-order reaction relative to substrate concentration. The first-order rate constants (k) were determined for CM degradation in dry air at 373, 383, 388 and 393 K, at air humidity RH=76.4% at 323, 333, 343 and 353 K, and at 353 K at air humidity RH>50%. The kinetic and thermodynamic parameters of the decomposition were calculated.     

甘草酸二铵18位差向异构体的核磁共振研究

目的对甘草酸二铵18位两种差向异构体的1HNMR、13CNMR谱信号进行全归属。方法应用COSY、TOCOSY、NOESY、HSQC、HMBC二维核磁共振技术,对甘草酸二铵两种异构体进行了测试。结果首次利用二维核磁共振技术对甘草酸二铵两种异构体的1HNMR、13CNMR谱信号进行了全归属。结论甘草酸二铵两种异构体的部分13CNMR谱数据差别较大,可作为区分两种异构体的一个指标。     

Structural identification and characterization of potential degradants of zotarolimus on zotarolimus-coated drug-eluting stents

Identification and characterization of unknown zotarolimus impurities on zotarolimus-coated drug-eluting stents is an important aspect of product development since the presence of impurities can have a significant impact on quality and safety of the drug product. Four zotarolimus degradation products have been characterized by LC/UV/PDA, LC/MS, LC/MS/MS and NMR techniques in this work. Zotarolimus drug substance and zotarolimus-coated stents were subjected to degradation under heat, humidity, acid or base conditions. The HPLC separation was achieved on a Zorbax Eclipse XDB-C8 column using gradient elution and UV detection at 278 nm. All four impurities generated through the degradation were initially analyzed by LC/MS and/or LC/MS/MS for structural information. Then the isolation of these degradants was carried out by semi-preparative HPLC method followed by freeze-drying of the collected fractions. Finally the degradants were studied by ¹H and ¹³C NMR spectrometry. Based on LC/MS, ¹H NMR and ¹³C NMR data, the structures of these impurities were proposed and characterized as zotarolimus ring-opened isomer (1), zotarolimus hydrolysis product, 16-O-desmethyl ring-opened isomer (2) and zotarolimus lower fragment (3). Degradants 1, 2 and 3 have been observed on degraded zotarolimus-coated stent products.     

Stability of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions

The stability and compatibility of clindamycin phosphate and ceftizoxime sodium, cefoxitin sodium, cefamandole nafate, or cefazolin sodium in two intravenous solutions were studied. Each antibiotic alone as well as each of the four two-drug combinations were examined when mixed in duplicate 100-mL glass bottles of 5% dextrose and 0.9% sodium chloride injections. Antibiotic concentration, pH, and visual appearance were recorded at the time of preparation and at 1, 4, 8, 12, 24, and 48 hours. Antibiotic concentrations were assessed with drug-specific high-performance liquid chromatographic assays. Decreases in concentration of 10% or more from the original concentration were considered to indicate instability. All the single antibiotic solutions were stable for 48 hours. Clindamycin was stable in all combinations except with ceftizoxime in 0.9% sodium chloride injection, which measured 89.3% of its original clindamycin concentration at 48 hours. All the cephalosporins mixed with clindamycin were stable for 48 hours. Clindamycin is stable for at least 48 hours when mixed with cefoxitin sodium, cefamandole nafate, or cefazolin sodium in either 5% dextrose or 0.9% sodium chloride injections and for at least 24 hours when mixed with ceftizoxime sodium in 0.9% sodium chloride injection.