Tetracyclines

Summary From butadiene-naphthoquinone adducts we prepared 1,2,3,4,4a,9a,-hexahydro-10-hydroxyanthrones with a 4a,9a,10-cis-cis configuration and with various functional groups in the 2- and 3-positions that are necessary for the further synthesis of compounds allied to natural 6-demethyltetracyclines.The authors thank L. B. Senyavina of the Institute for the Chemistry of Natural Products of the Academy of Sciences of the USSR for carrying out the spectroscopic measurements.     

Flow Injection Chemiluminescence Determination Of Tetracyclines

Abstract

A fast and simple flow injection chemiluminescence method for the determination of trace amounts of tetracyclines is proposed based on the chemiluminescence of the KMnO₄ - TCs redox reaction in acidic medium in the presence of a sensitizer, OP. The response to the concentration of tetracyclines is linear in the range of 1.00 to 1000 μg mL^?1 with a relative standard deviation < 2.3 % for determination of 50.0 μg mL^?1 of each antibiotic (n = 11). The detection limits for tetracycline, oxytetracycline and chlortetracycline are 0.40, 0.52 and 0.60 μg mL^?1, respectively. The recommended method is suitable for automatic and continuous analysis and has been successfully tested for determination of tetracyclines in commercial formulations. The chemiluminescence intensity was found to be remarkably enhanced when in the presence of OP micellar system; possible reasons for this observed micellar induced enhanced chemiluminescence is given.     

四环素C-2位Mannich反应的研究

报道了四环素C-2位与伯胺、仲胺反应形成Mannich碱的简便方法:四环素盐酸盐在甲醇和水溶液中与伯胺反应,生成二级Mannich碱;四环素在叔丁醇中与仲胺反应,生成三级Mannich碱。合成了10个化合物,其中8个未见报道,并对所合成化合物的结构进行了表征。     

Chemiluminescence Determination of Tetracyclines via Aluminum Sensitized Fluorescence

Tetracycline, oxytetracycline, doxycycline, and chlortetracycline have been determined by chemiexcitation of the corresponding Al(III) highly fluorescent complex from the permanganate or cerium(IV)-sulphite chemiluminogenic reactions. Limits of detection and ranges of linearity are equal to 0.024, 0.015, 0.014, and 0.050 µg mL^?1 and 0.067–3.20, 0.042–1.70, 0.042–3.00, and 0.103–2.80 µg mL^?1 for tetracycline, oxytetracycline, doxycycline, and chlortetracycline, respectively. Average recovery of tetracyclines from solutions of commercial formulations was equal to 99.8% and the procedure was successfully applied to the determination of tetracyclines in commercial products with mean relative error equal to 3.4% (range 1.4–5.0%).     

Tetracyclines: Chemistry,Biochemistry, and Structure-Activity Relations

Tetracycline antibiotics continue to play an important role in human and veterinary medicine and in animal nutrition. The classical tetracyclines obtained by fermentation have been supplemented by products of partial synthesis which provide, in particular, the advantages of better pharmacokinetic properties and greater tolerance. Following a brief review of older work, the present article describes partial and total syntheses of tetracyclines, the influence of electronic, steric, and lipophilic factors and of complex formation on biological activity. The inhibition of biochemical systems invoked in interpretation of the mode of action of tetracyclines and problems involved in the development of resistance are discussed.     

动物源性食品中四环素类残留分析研究进展

综述了检测动物源性食品中四环素类残留的前处理方法,包括固相萃取、固相微萃取、基质分散技术、分子印迹技术、限进介质材料;对高效液相色谱、毛细管电泳、微生物法和酶联免疫分析等在四环素类药物中的检测应用进行了综述,比较了各种方法的优缺点。     

胶束毛细管电泳法同时分离四环素与青霉素类药物的研究

采用胶束毛细管电泳(MEKC),建立了四环素(TCs)和青霉素(PENs)两类7种药物同时分离的方法。考察了MEKC中缓冲液类型、离子浓度和pH值,以及表面活性剂(SDS)浓度、分离电压、温度等参数的影响。利用L16(45)正交试验,确立了最佳的电泳条件:缓冲液为40 mmol/L磷酸二氢钾-20 mmol/L硼砂,添加65 mmol/L SDS,pH 7.9,分离电压28 kV,分离温度28℃,紫外检测波长分别为350 nm和200nm。结果表明:7种药物在25 min内得到完全分离。在1.56~50 mg/L范围内呈良好的线性关系,相关系数(r2)为0.997 9~0.999 9,峰面积的相对标准偏差(n=6)为4.1%~7.3%;迁移时间的相对标准偏差(n=6)为0.33%~0.67%。在2.0,5.0,10.0 mg/kg的加标水平下,7种药物的回收率为83.6%~93.3%,相对标准偏差(n=6)为4.7%~7.6%。该法快速、简便、准确,具有较高的灵敏度,已应用于合肥市及周边地区水塘和湖水中7种药物的快速分离检测。     

反相高效液相法测定四环素类抗生素

 利用高效液相法 ,在C18柱上以甲醇 乙腈 0 0 1mol/L草酸溶液 (pH 2 0 ) (体积比为 11∶2 2∶6 7)为流动相 ,采用 2 6 7nm紫外光进行检测 ,在 2 2min内将 7种四环素类抗生素全部洗脱并达到基线分离。探讨了流动相的pH值、草酸的浓度、流动相中有机相的比例以及检测波长等因素对分离度和灵敏度的影响。采用标准加入法定量 ,对两种实际样品进行了分析。结果表明 :该方法操作简单、灵敏度高、定量准确。     

离子液体溶剂浮选-光度法测定水中痕量四环素类抗生素

将离子液体应用于气浮溶剂浮选分离/富集四环素类抗生素(TCs),建立了一种离子液体1-丁基-3-甲基咪唑六氟磷酸盐(\PF6)取代传统有机溶剂气浮溶剂浮选分离/富集四环素类抗生素的新方法.TCs与镧能形成疏水性络合物,易于浮选至离子液体相,考察了在离子液体中加入有机溶剂的种类和体积,试液的pH值、La的加入量、气体流速、浮选时间以及共存物质对浮选效率的影响,优化了浮选条件,与溶剂萃取方法相比,离子液体溶剂浮选四环素类抗生素富集倍数高,且无毒,无污染,试剂用量少,实测了鱼塘水和辽河水样,RSD分别为3.0%和4.3%(n=5),回收率为97%.本方法适合于环境水样中痕量四环素总量的分析检测.     

肌肉组织中四环素类抗生素的固相萃取-液相色谱法测定

建立了四环素类抗生素的高灵敏度测定方法，通过对实验条件的优化，采用固相萃取-反相高效液相色谱法同时测定肌肉组织中的土霉素(oxytetracycline)、四环素(tetracycline)、金霉素(chlortetracycline)3种四环素类抗生素残留量；土霉素、四环素、金霉素的检出限分别为20、40、100μg／kg；方法相对标准偏差为5．1％-7．1％(n＝5)，平均回收率为80％—82％。     

Determination of Tetracyclines in Water Samples Using Liquid Chromatography with Fluorimetric Detection

A liquid chromatographic method with fluorimetric detection is proposed for the determination of trace levels of oxytetracycline, tetracycline, chlortetracycline and doxycycline in water samples. The analytes are preconcentrated by solid phase extraction using reversed phase polymeric cartridges and acetonitrile as eluent. Preconcentration factors up to 125 can be obtained. The chromatographic separation is performed on a polymeric column with a gradient elution program using mobile phases based on mixtures of acetonitrile and 0.01 mol L^?1 oxalic acid aqueous solution at a flow rate of 1.2 mL min^?1. Tetracyclines are post-column derivatized with a reagent solution consisting of 0.1 mol L^?1 Mg(II) at pH 9 at a flow rate of 0.6 mL min^?1. The highly fluorescent Mg(II) chelates are detected at λ _ex = 374 nm and λ _em = 499 nm. The detection limits of the whole process are in the low μg L^?1 level. The proposed method has been applied to the analysis of spiked natural water samples, and recovery rates higher than 80% have been obtained.     

饲料中四环素类药物含量的高效液相色谱测定

建立了高效液相色谱法测定饲料中四环素类药物含量的方法。样品经甲醇-盐酸溶液提取,WatersOasis HLB固相萃取柱净化,进行HPLC分析。标准校正曲线线性范围为0.05~2.0 mg/L,相关系数r>0.999。饲料中土霉素、四环素、金霉素和强力霉素的定量下限(LOQ)依次是2.0、2.0、4.0和4.0 mg/kg;不同添加水平样品加标回收率为78%~103%,RSD小于11%。     

反相高效液相色谱法快速测定7种四环素类抗生素

建立了一种反相高效液相色谱梯度洗脱分离测定四环素类药物的新方法。采用DiamonsilTM C1 8ODS(2 5 0mm× 4 .6mmi.d ,5 μm)色谱柱 ,以甲醇 乙腈 0 .0 1mol/L草酸为流动相 ,流速 1.0mL/min ,2 70nm检测 ,在10min内分离检测四环素等 7种化合物。同时还研究了流动相组成、梯度条件、pH值、草酸浓度等因素对分离效果的影响。     

改性植物生物炭去除水中四环素类抗生素的研究进展

四环素类抗生素滥用和缺乏有效去除技术导致广泛残留并诱导产生耐药细菌,已成为世界环境问题之一.植物生物炭具有来源广、成本低、易制备、资源有效利用和环境友好等优点,在环境修复领域,特别是抗生素污染物去除方面备受关注.本文综述了改性植物生物炭对四环素类抗生素的去除效果,讨论环境因素对改性生物炭性能的影响并深入探讨去除机制,分...     

养殖废水中四环素HPLC分析方法的研究

为了评价养殖废水中四环素类抗生素残留的状况,建立了养猪场废水中四种常见四环素类抗生素(土霉素、四环素、金霉素、强力霉素)的高效液相色谱分析方法.水样中四环素类药物经HLB固相萃取小柱吸附,甲醇乙酸乙酯溶液洗脱后用高效液相色谱紫外检测器测定.在0.05～10.00 μg/mL.范围内,四种抗生素的峰面积与质量浓度的线性关...     

Tetracyclines adsorption onto alumina: A comparative experimental and molecular dynamics simulation study

Using alumina (Al₂O₃) as the adsorbent, a static adsorption experiment was carried out in this study. It comprehensively evaluated the factors including Al₂O₃ dosage, adsorption temperature, and pH that influence the adsorption capability of three tetracyclines (TCs), namely, tetracycline hydrochloride (TC), chlortetracycline hydrochloride (CTC) and oxytetracycline hydrochloride (OTC). The results demonstrate that the adsorption efficiency increases with Al₂O₃ dosage. In addition, low-acid or natural solution is benefit for the adsorption. The adsorption behavior is more reasonably described with the Freundlich isotherm, and fits well with the pseudo-second-order kinetic model (R²?>?0.999). The results of molecular dynamics (MD) simulation show that the structures of TCs deformed during the combining process. The values of binding energy of TCs follow the order as: CTC (88.45?kcal/mol)?>?OTC (73.54?kcal/mol)?>?TC (54.28?kcal/mol). The MD simulation results agree well with the adsorption experimental results, which indicates that the MD simulation is reliable and reasonable. The MD simulation will provide theoretical knowledge in understanding the adsorption mechanism and environmental behavior of TCs.     

Ni电极电化学流通池检测四环素类药品的研究

比较Au、GC和Ni电极对四环素的电化学响应,讨论了纯Ni电极对四环素的电催化氧化特性,提出以纯Ni为工作电极的电化学流通池,优化结构,建立了测定四环素类抗生素的电化学流通池安培检测法.该方法对四环素、土霉素和强力霉素都有较高的响应灵敏度,线性范围0.1～15mg/L.最低检出限分别为35、45和43μg/L.用此方法可以直接测定四环素类药品的含量.     

Determination of Tetracyclines in Milk by Graphene-Based Solid-Phase Extraction and High-Performance Liquid Chromatography

A graphene-based solid-phase extraction (SPE) column was prepared for the isolation of tetracyclines from milk followed by determination by high-performance liquid chromatography. Graphene provided better separation for tetracyclines than amine-modified graphene and carboxyl-modified graphene. The optimized graphene-based SPE column showed high absorption capacities (greater than 4,660?ng) and high recoveries (exceeding 92%) for tetracycline, oxytetracycline, chlortetracycline, and doxycycline and was successfully reused at least fifty times. The limits of detection in milk were from 10 to 20?ng/mL, with recoveries between 82.3 and 103.6%. Furthermore, the system showed superior performance than two commercial SPE cartridges with respect to recovery, purification, and reusability. Therefore, this approach is suitable for the determination of tetracyclines in milk.     

Determination of Tetracyclines in Milk with a Molecularly Imprinted Polymer-Based Microtiter Chemiluminescence Sensor

A molecularly imprinted polymer (MIP) capable of recognizing five tetracyclines using minocycline as the template was synthesized for the first time. The MIP was employed as the recognition reagent to prepare a chemiluminescence sensor on a conventional microtiter plate. The light signal was initiated using the highly efficient bis(2,4,6-trichlorophenyl) oxalate-hydrogen peroxide-imidazole chemiluminescence system. After optimization of several appropriate factors, the sensor was employed to determine five tetracyclines in milk. The developed assay contained only one sample-loading step, so each measurement was completed within 12?min. The limits of detection for these analytes were in the range from 0.5 to 2.0?pg/mL, while the recoveries from the fortified milk samples were between 78.1 and 105%. In addition, the sensor was shown to be reusable for up to four measurements. Hence, this sensor has been demonstrated to be a simple, rapid, sensitive, and durable tool for the determination of tetracyclines in animal-derived food.     

牛肉中5种四环素类兽药残留的UPLC-MS/MS检测

四环素族(tetracyclines,TCs)抗生素为氢化骈四苯的衍生物,是一类从链霉菌属微生物代谢产物中提取或半人工合成的广谱抗菌药物,主要用于治疗支原体、衣原体等致病源引起的感染,目前在畜禽生产中广泛使用.