Simultaneous kinetic spectrophotometric determination of cephalexin and trimethoprim in pharmaceutical preparation and human urine with the aid of chemometrics

A procedure for the simultaneous kinetic spectrophotometric determination of cephalexin and trimethoprim was described. It was based on the different reaction rate of oxidation of these compounds with yellow ammonium cerous （Ⅳ） sulfate in acidic medium and colorless cerous （Ⅲ） sulfate was produced. The overlapped kinetic data was quantitatively resolved by the use of chemometric methods, partial least squares （PLS）, principal component regression （PCR） and radial basis function-artificial neural network （RBF-ANN）. The proposed method was also applied to the simultaneous determination of cephalexin and trimethoprim in pharmaceutical preparation and human urine with satisfied results, which compared well with those obtained by HPLC.

The effect of cephalexin in influencing the pharmacokinetics of a novel drug–5’-valyl-cytarabine hydrochloride

The aim of this study is to investigate the pharmacokinetics of 5′-valyl-cytarabine hydrochloride(OPC) when co-administered with cephalexin, which are both the substrates of PepT 1.The drugs were administered orally by gavage. Blood samples were collected from the orbital plexus of the rats after oral administration of drug solutions. A new high-performance liquid chromatographic method was validated and used for determination of the two drugs. Pharmacokinetic parameters were calculated using DAS 2.1.1 software with noncompartmental analysis. After oral administration of OPC and co-administration of OPC and cephalexin,there were significant differences in the main pharmacokinetic parameters. The main pharmacokinetic parameters for the OPC group and the co-administrative group were as follows:AUC0-10(18,168.7 ± 2561.4) ng·h/ml and(13,448.5 ± 2544.73) ng·h/ml, AUC0-∞(18,683.1 ± 3066.5)ng·h/ml and(13,721.1 ± 2683.0) ng·h/ml, Cmax(6654.8 ± 481.3) ng/ml and(4765.1 ± 928.9) ng/ml, respectively. The results showed that the bioavailability of OPC could be reduced when co-administered with cephalexin, suggesting that the efficacy of a novel drug might be reduced when it came to combination use of β-lactam antibiotics.

Ultrasound assisted crystallization of cephalexin monohydrate:Nucleation mechanism and crystal habit control

With the high-quality requirements for cephalexin monohydrate,developing a robust and practical crystallization process to produce cephalexin monohydrate with good crystal habit,appropriate aspect ratio and high bulk density as well as suitable flowability is urgently needed.This research has explored the influence of ultrasound on crystallization of cephalexin monohydrate in terms of nucleation mechanism and crystal habit control.The results of metastable zone width and induction time measurement showed the presence of ultrasound irradiation can narrow the metastable zone and shorten induction time.Cavitation phenomena generated by ultrasound were used to qualitatively explain the mechanism of ultrasound promoting nucleation of cephalexin monohydrate.Furthermore,on the basis of classical nucleation theory and induction time data,a series of nucleation-related parameters(such as crystalliquid interfacial tension,radius of the critical nucleus and etc.)were calculated and showed a decreasing trend under ultrasound irradiation.The diffusion coefficient of the studied system was also determined to increase by 72.73%under ultrasound.The changes in these parameters have quantitatively confirmed the mechanism of ultrasound influence on the nucleation process.In further,the calculated surface entropy factor has confirmed that the growth of cephalexin monohydrate follows continuous growth mechanism under the research conditions of this work.Through the exploration of crystallization conditions,it is found that suitable ultrasonic treatment,seeding,supersaturation control and removal of fine crystals are conducive to improving the quality of cephalexin monohydrate product.Optimizing the crystallization process coupled continuous ultrasound irradiation with fine-crystal dissolution policy has achieved the controllable production of monodisperse cephalexin monohydrate crystal with good performance.

Radioiodination of Cephalexin with ¹²⁵I and Its Biological Behavior in Mice

A procedure for radioiodination of Cephalexin with iodine-125 was carried out via an electrophilic substitution reaction. Using 3.7 MBq of Na125I, 200μl of cephalexin as substrate, 200 μl of iodogen as oxidizing agent in acetone at 40°C for 20 min, a maximum radiochemical yield of 125I-Ceph (95%) was obtained. The labeled compound was separated and purified by means of high-pressure liquid chromatography (HPLC). The biological distribution in normal and inflamed (septic and aseptic) mice indicates the suitability of radioiodinated cephalexin for imaging of

Sorption removal of cephalexin by HNO_3 and H_2O_2 oxidized activated carbons

Cephalexin＇s traces within pharmaceutical effluents have toxic impact toward ecological and human health. Low-cost activated carbon derived from Trapa natans husk was oxidized with hydrogen peroxide and nitric acid, and tested for their ability to re- move cephalexin from aqueous solutions. Oxidization with H202 showed negative effect on the cephalexin sorption, whereas HNO3 oxidization improved the adsorption. The cephalexin adsorption isotherms on the native and HNO3 oxidized carbons correlated well with the Freundlich equation while their kinetics followed the pseudo-second order model. The removal of cephalexin by the native and HNO3 oxidized carbons was found to be most favored at low ionic strength and strong acidic conditions. Based on the thermal and FTIR analyses, the interaction mechanisms of the interaction between cephalexin and the carbons were proposed. Electrostatic attraction, hydrophobic interaction and chemical bonding with surface functional groups were demonstrated as primary mechanisms for cephalexin removal. The nitrogen functionalities on the carbon surface were considered to be an important factor affecting the adsorption process.

头孢氨苄胶囊溶出曲线一致性研究

目的:建立头孢氨苄胶囊一致性评价方法。方法:采用篮法,转速100 r/min,分别以水、0.1 mol/L盐酸、pH4.5磷酸盐缓冲液和pH6.8磷酸盐缓冲液为溶出介质,溶出介质体积为900 mL;采用紫外法测定头孢氨苄胶囊溶出度,并计算其累积溶出量,绘制相应溶出曲线;评价溶出曲线的相似度。结果:在4种不同pH的溶出介质中,仿制产品和参比样品均在15 min内溶出量达到了85%以上,说明仿制产品与参比样品溶出行为基本一致,判定相似。结论:本方法可为头孢氨苄胶囊的质量一致性评价提供参考。

头孢氨苄降解产物荧光性质的研究及分析应用

详细研究了头孢氨苄在酸、碱介质中的降解反应，建立了酸、碱降解的荧光分析法．线性范围是０．５０～１００ｎｇ／ｍＬ（酸降解）和２．０～７０ｎｇ／ｍＬ（碱降解）．从精密度和准确度看，酸降解优于碱降解的荧光分析．将酸降解荧光分析法应用于血清和尿样中头孢氨苄的测定，结果良好．

光化学荧光分析法测定头孢氨苄的研究

在pH4.0的缓冲溶液中,头孢氨苄在紫外光照射下能发生光化学反应,形成具有荧光的产物,λ_(ex)为345nm,λ_(em)乙为432nm。在头孢氨苄浓度为0.1～4.0μg/ml范围内,荧光强度与浓度呈良好的线性关系,由此建立了头孢氨苄的光化学荧光测定法。方法的检出限为0.01μg/ml,相对标准偏差为0.93％。本法简便、快速且灵敏度高,可用于尿液中头孢氨苄含量的测定。

固定化青霉素酰化酶在DMSO-水介质中催化合成头孢氨苄

与传统的化学方法相比较 ,酶法合成头孢菌素工艺具有明显优点 ,通过酶的固定化与非水相酶催化技术相结合为提高产率找到了简捷的途径。实验以 7 氨基 3 脱乙酰氧基头孢烷酸 (7 amino 3 deactoxycephalosporanic,7 ADCA)为母核 ,苯甘氨酸甲酯盐酸盐 (D phenylglycinemethylesterchlorohydrate ,PGME)为酰基供体 ,在二甲亚砜 (DMSO) 水共溶剂体系中 ,采用聚丙烯腈纤维固定化青霉素酰化酶 (penicillinacylaseEC3 .5 .1.11,PA)催化合成头孢氨苄 (Cephalexin)。发现DMSO浓度、反应温度、pH、底物浓度等对转化率均有影响。在 2 5℃ ,pH6 .5 ,40 %DMSO 水体系中 ,7 ADCA、PGME浓度分别为 85mmol/L ,12 8mmol/L时 ,7 ADCA转化率达 90 %。在 15次反复合成Cephalexin期间 ,转化率保持 90

头孢氨苄的分光光度测定

采用分光光度法测定头孢氨苄的含量，较已有方法灵敏、准确（εｍａｘ＝７．６５×１０４Ｌ／ｍｏｌ·ｃｍ），０～４．１４μｇ／ｍｌ的最后溶液符合Ｂｅｅｒ定津，变异系数为３．１９％，平均回收率１００．４％，测定片剂和胶囊结果甚好。

流动注射化学发光法测定头孢氨苄

基于头孢氨苄 (CEX)降解产物中有还原性的巯基 (SH)基团 ,在 0 .2 mol/ L 的 H2 SO4介质中 ,能与Ce( )产生化学发光反应 ,罗丹明 6 G可敏化其发光强度 ,结合流动注射技术 ,考察了本体系的化学发光条件 ,建立了一种测定头孢氨苄的化学发光新方法。该法线性范围为 0 .0 5— 10 .0 μg/ m L,相关系数 r=0 .9984 ,检出限为 0 .0 2 μg/ m L,对 1.0 μg/ m L的头孢氨苄标准溶液进行连续 9次平行测定 ,相对标准偏差为 1.4 %。

头孢氨苄缓释片在健康人体内的生物利用度和药物动力学

目的:比较头孢氨苄缓释片和普通胶囊的生物利用度和药物动力学。方法：10例健康志愿者分别单剂量口服500mg头孢氨苄缓释片和普通胶囊，血药浓度测定方法为HPLC法。结果：两种剂型体内过程均符合一室开放模型，缓释片的达峰时间（Tmax）为（2．58±0．59）h，峰浓度（Cmax）为（10．08±1．68）μg／ml．吸收速率常数（Ka）为（0．90±0．53）／h，消除速率常数（Ke）为（0.26±0.02）／g，半衰期（T1／2）为（2.67±0.23）h，清除率（Cl）为（6.93±1.71）L／h，分布容积（Vd）为（26.66±6.72）L，药一时曲线下面积（AUC）为（48.31±9.32）μg·h／ml。两种剂型T一C一Ka、Ke、T1／2和Cl均存在显著性差异（P＜0．01），Vd、AUC无显著性差异（P＞0．05）；缓释片的相对生物利用度为（104．90±8．35）％。结论：缓释片的吸收减慢，Tmax推迟，T1／2延长，可减少服药次数，提高药物治疗的顺应性。

固定化巨大芽孢杆菌青霉素G酰化酶酶促合成头孢氨苄的研究

β—内酰胺系列抗菌素抗菌谱广、疗效高、毒副作用小,国际上研究与应用日渐广泛深入。头孢氨苄(Cephalexin)是重要的半合成抗菌素之一,由头孢霉素母核7—氨基脱乙酰氧基头孢烷酸(简称7-ADCA)和侧链结构物苯甘氨酸或其甲酯(PGME)经酰化而生成。酰化有化学法和酶法两种。采用青霉素G酰化酶或a—氨基酸酯酶或,a—氨酰转移酶的酶法,具有工艺操作简单、无需基团保护、环境污染轻等优点。继日本人于70年代初试验成功酶法之后,80年代初我们开展了这方面研究。制备方面,胞外酶优于胞内酶;使用方面,固定化酶优于固定化细胞。在用具有青霉素G酰化酶活性的固定化大肠杆菌(Escherichia coli)细胞合成头孢氨苄的基础上,又研究了用固定化巨大芽孢杆菌(Bacillus megaterium)BP931胞外青霉素G酰化酶酰化合成头孢氨苄的条件。本文报道这一研究结果。

银微盘电极上头孢氨苄降解产物的伏安行为及其应用

基于头孢氨华（ＣＥＸ）降解产物中含有巯基（－ＳＨ），能与Ａｇ＋生成难溶化合物的特性，在银微盘电极上研究了ＣＥＸ降解产物的伏安行为，探讨了电极反应的机理。运用示差脉冲溶出伏安法，在０．１ｍｏｌ／Ｌ ＨＡｃ－ＮａＡｃ介质中，ＣＥＸ降解产物的还原峰电流与ＣＥＸ浓度于８．０×１０－８～７．０×１０－６ｍｏｌ／Ｌ范围内呈良好线性关系；检测限为１．０×１０－８ｍｏｌ／Ｌ；测定头孢氨苄胶囊中ＣＥＸ．含量为９２．０％，与药典法比较，相对误差为３．４％。

臭氧氧化降解水中头孢氨苄的效能与机理研究

研究了臭氧对难降解的头孢氨苄(CLX)的氧化效果,考察臭氧投加量、pH、腐殖酸、自由基抑制剂对反应的影响。结果表明,当反应的化学计量比达到1.1([O3]=1.5 mg/L,[CLX]=10mg/L)时,反应10min,CLX的降解率达到96.67%。碱性条件下,OH-离子的增加促进了臭氧分解产生OH,有利于臭氧氧化水中CLX,当CLX初始浓度为10mg/L,臭氧投加量为1.0mg/L,水样pH为2.5时,CLX的降解率仅为26.11%;水样pH增到10.0时,CLX的降解率增到91.26%。腐殖酸对臭氧氧化CLX的影响与腐殖酸的浓度有关,低浓度(2.5mg/L)时对臭氧氧化CLX效果有所促进,其降解率提高了4.73%;高浓度时,抑制臭氧氧化反应,且随着腐殖酸浓度的提高,CLX降解效果逐渐降低,当腐殖酸浓度达到20mg/L时,CLX的降解率仅有28.55%。·OH抑制剂叔丁醇对臭氧氧化去除CLX具有明显的抑制作用,当叔丁醇浓度大于50mg/L后,CLX的降解率仅约为12%。

混合线性分析法的原理及应用

对一种新近发展的多元校正方法———混合线性分析法 (hybridlinearanalysis,HLA)的原理进行了深入探讨和阐述 ,用该法进行了模拟体系和复方头孢氨苄制剂的分析 ,在主因子数确定、单位谱的获得、波长选择、适用范围等方面进行了讨论。结果表明 :HLA法可给出优于偏最小二乘法 (PLS)的结果 ,方法易行 ,结果准确 。

头孢氨苄缓释小丸的初步研究

用膜控法制备头孢氨苄缓释小丸制剂,其体外溶出符合零级动力学过程(k_r=13.5mg/h)。在不同介质中其释药速率不同;释药速率与小丸的衣膜增重百分率的倒数成线性关系;体内动力学过程符合一室开放模型,血药浓度数据经 PKBP—Nl 计算机程序处理,求得 k_α=0.845h^(-1),k_e=0.641h^(-1),tmax=2.338h,Cmax=6.648μg/ml。体内外数据具有显著的相关性。

动物性食品中头孢氨苄残留检测研究进展

头孢氨苄属于人兽共用β-内酰胺类抗生素,在兽医临床上应用广泛。介绍了头孢氨苄的性质、危害及国内外主要的检测方法和技术,包括紫外分光光度法、高效液相色谱法、液质联用、毛细管电泳法、酶联免疫吸附法、荧光偏振免疫法、免疫层析法,并对头孢氨苄残留分析前景进行了展望。

反胶束体系中酶法合成头孢力新的动力学

利用来自Xanthomonas citri的酰化酶由D-α-苯甘氨酸甲酯和7-ADCA合成头孢力新是典型的动力学控制合成过程,其中既有产物的合成又有产物和底物（D-α-苯甘氨酸甲酯）的水解。动力学分析表明,反应置于反胶束体系将不仅提高酶的催化速度而且提高转移酶活力对水解酶活力的选择性。利用AOT/异辛烷反胶束体系酶法合成头孢力新使水解副反应被抑制,合成途径被强化。水成为反胶束酶反应体系中重要的调节手段,它对反应速度呈“铃形”关系。

四种口服头孢菌素的体外抗菌活性的比较研究

本文报道口服Cefixime对900株需氧菌和厌氧菌的体外抗菌作用,并与其它口服的头孢克罗、头孢羟氨苄和头孢氨苄进行了比较。Cefixime对链球菌具较强作用,但对葡萄球菌的作用较差;对肠球菌无效。对肠杆菌科细菌的抗菌活性四者之中以Cefixime最强。Cefixime对头孢氨苄耐药株仍具高度活性,其MIC均值可降低60～1200倍以上。绿脓杆菌、硝酸盐阴性杆菌、鲁氏不动杆菌和产碱杆菌对Cefixime和其它3种头孢菌素的敏感性均较差。四者对厌氧菌的作用除厌氧球菌外其抗菌活性都很弱。Cefixime对β-内酰胺酶稳定,口服吸收良好,抗菌作用强,是一个值得进行临床研究的口服头孢菌素。