摘要
喹诺酮类药物是用于泌尿、呼吸道、胃肠道。骨关节及皮肤等多种组织感染的抗微生物药物,近年来得到广泛的应用,但是滥用喹诺酮类药物,不仅增加了生物的抗药性,还给环境造成了一定的影响,危害到人们的健康,因此,建立一种简单、灵敏、快速、准确的测定喹诺酮类药物的方法非常必要,本文根据喹诺酮类药物的化学发光行为,建立了流动注射化学发光测定喹诺酮类药物的分析方法,并对机理进行了探讨,对以后的工作奠定了一定的基础。全文分为:
第一章:论述了化学发光分析法的历史及原理,并介绍了对喹诺酮类药物的研究进展。
第二章:提出了测定恩诺沙星的化学发光新方法,采用恩诺沙星-KMnO4-Na2S2O3-H2SO4化学发光体系,成功的测定了恩诺沙星注射液和片剂中恩诺沙星的含量,回收率在97.3%-105.1%和90.1%~103.6%之间,结果令人满意。
第三章:研究了新的化学发光体系-Ag(Ⅲ)-H2SO4,并用于恩诺沙星的测定,试验中不仅测定了片剂及注射液中恩诺沙星的含量而且对此体系的机理进行了探讨,建立了快速灵敏的测定恩诺沙星的化学发光新方法。
第四章:利用诺氟沙星对Ag(Ⅲ)-H2SO4体系的增敏作用,我们建立了测定诺氟沙星的化学发光方法,该方法检出限为3.097×10-9g/mL,对2.0×10-7g/mL诺氟沙星进行11次平行测定,相对标准偏差为1.7%。回收率在95.0%-104.0%.利用该方法测定了血清,尿液和胶囊中诺氟沙星,结果令人满意。
Quinlones are the new generation broad-spectrum antibities used in the treatment of infections of urinary tract, respiratory tract, gastroenteritis, skin and skin structures infections, they are developed quickly and widely used for clinic in recent years, but this result in not only the environment to be contaminated, but also the resistence to be increased, even endenger for the human life. Thus, it is necessary to studied and founded the quick and sensitive analysis methods of quinlones. This thesis studies the chemiluminescence (CL) behavior of quinolones, and used the flow injection CL methods for the determination of some quenolones. The CL mechanism was discussed. This dissertation includes four chapters as follows:
Chapter 1:The history and fundamental principle of CL method are reviewed and introduced the CL methods for quinolones in details.
Chapter 2:A chemiluminescence system-enrofloxacin - KMnO4- Na2S2O3 - H2SO4, was developed for the determination of enrofloxacin. The method has been applied to the determination of enrofloxacin tables and injections with satisfied results. and the recovery is between 97.3%-105.1% and 90.1%~103.6%.
Chapter 3:The chemiluminescence reaction of Ag (Ⅲ)-H2SO4 system was studied. Based on it, a new method for the determination of enrofloxacin was developed. In this enperiment, we determined the enrofloxacin tables and injections and discussed the the mechinism.
Chapter 4:Norfloxacin can enhance the CL signals of Ag (Ⅲ)-H2SO4 system, a novel rapid flow injection method with chemiluminescence detection was established for the determination of norfloxacin. The detection limit was 3.097×10-9g/mL, and the relative standard deviation (n=11) is 1.7%at 2.0×10-7g/mL. The recovery was 95.0%~104.0%, This method was used for the determination of norfloxacin in the serum, urine and capsule with satisfactory results.
引文
[1]Radziszewski B.Chem Ber,1877,10:70.
[2]Albrecht H O, Z Phys Chem,1928, A136:321.
[3]Gleu K, Petsh W.Z Angew Chem,1935,48:57.
[4]章竹君,化学通报,1976,(4):30.
[5]Lin J-M, Zhang F, Chin J Chem,1991,9:499.
[6]Lin J-M, An J.Chin J Chem,1992,10 (5):417.
[7]马玉凤.流动注射分析仪及其分析方法发展现状[J].仪器仪表用户,2004,11(4):4-6.
[8]熊少华.流动注射分析的应用[J].有色冶金设计与研究,2003,24(4):19-21.
[9]周红伟,汤志勇.流动注射化学发光分析法的应用进展[J].安徽化工,2005,6:2-4.
[10]杨秋青,朱智.甲流动注射化学发光分析技术的最新应用[J].河北师范大学学报(自然科学版),2005,29(6):600-605.
[11]王世全,聂珍贵.喹诺酮类药物的研究进展[J].药物与临床,2006,3(12):84-86.
[12]姜利英,谢小品,崔光照,任景英,姚斐斐.动物性食品中喹诺酮类药物残留检测方法的研究进展[J].郑州轻工业学院学报(自然科学版),2008,23(4):1-5.
[13]Kerman L, Hoof J V, Debeyckelaere W, etal Evaluation of the European fourplate test as a tool for screening antibiotic residues in meat samples from retail outlets[J].AOAC Int,1998,81 (1):51.
[14]黄晓蓉,郑晶,李寿崧等.鳗鱼及其制品中喹诺酮类药物残留的微生物快速检测方法研究[J].淡水鱼业,2005,35(4):3.
[15]Wu S W, Wu H L, Chen S H. Derivatization gas chromatographic analysis of nalidixic acid in tables[J]. J Chinese Chem Soc,1987,34:7.
[16]姚如心,许庆琴,杜黎明.衍生化气相色谱法测定药物制剂中的培氟沙星[J].分析试验室,2005,24:59.
[17]Jeffery R M, Verdel K D, Willam H, etal Liquid chromatographic determination of sarfbxacin residues in channel catfish muscle [J].AOAC Int,1994,77 (4):871.
[18]谢恺舟,张军,龚道清等.鸡组织中环丙沙星残留的HPLC法测定研究[J].中国卫生检验杂志, 2001,11(6):651.
[19]刘靖靖,林黎明,江志刚等.高效液相色谱法同时检测8种喹诺酮类兽药残留量[J].分析试验室,2007,26(8):5.
[20]Duan J H, Yuan Z H. Development of an indirect competitive ELISA for ciprofloxacin ersidues in food animal edible tissues[J]. J Agric Food Chem,2001,49 (9):1696.
[21]曹立民,林洪,隋建新等.一种快速检测食品中氟喹诺酮类药物残留的方法[P].中国:200510044229.6,2006-02-08.
[22]Matthias F, Agnieszka K, Thuy D T V, etal Improved capillary electrophoretic separation of nine (fluoro) quinolones with fluorescence detection for biological and environmental samples[J].J Chromatogr A,2004,1047:305.
[23]Katarzyna M, Genowefa P, Stefan T. Determination of ciprofloxacin and its impurities by capillary zone electrophoresis[J].J Chromatogr A,2004,1051:267.
[24]Guido E P, Graziella C, Ettore C. Electrochemical sensor for the detection and presumptive identification of quinolone and tetracycline residues in milk[J]. Anal Chim Acta,2004,520:13.
[25]Magno A G T, Glaycia M S, Valdir S F. Determination of moxifloxacin in tables and human urine by squarewave adsorptive voltammetry[J]. Microchemical Journal,2005,81:209.
[26]应翔宇,杨永胜.兽用新型抗菌药物—恩诺沙星[J].中国兽药杂志,1995,29(3):53-56.
[27]中国兽药典委员会.中华人民共和国兽药典2000年版一部[S].北京:化学工业出版社,2000,186-189.
[28]仲晓宁,张璇,巩相莲.双波长紫外分光光度法测定复方恩诺沙星可溶性粉中恩诺沙星和盐酸多西环素的含量[J].中国兽药杂志,2005,39(9):26-28.
[29]顾明芬.紫外分光光度法测定恩诺沙星可溶性粉含量[J].天津畜牧兽医,1996,13(4):27-30.
[30]农英相,郑永娇.紫外分光光度法快速测定恩诺沙星注射液的含量[J].中国兽药杂志,2002,36(5):49.
[31]朱林,王苏华.紫外分光光度法测定恩诺沙星油剂注射液含量[J].兽药与饲料添加剂,2003,8(5):31-32.
[32]付林,刘丙云,商军.系数倍率紫外分光光度法测定赛鸽用复方恩诺沙星胶囊的含量[J].中国兽药杂志,2007,41(05):31-33.
[33]国家药典委员会.中华人民共和国药典2005年版[M].北京:化学工业出版社,2005.
[34]商军,王蓓,华贤辉,等.高效液相色谱法测定赛鸽用复方恩诺沙星胶囊中恩诺沙星和甲氧苄啶的含量.中国兽药杂志,2005,39(8):7-10.
[35]刘红,曾振灵,杨桂香,等.恩诺沙星ELISA快速检测方法的建立[J].中国兽药杂志,2006,40(11):13—15.
[36]贾丽华,曾晓丹,王清滨,等.胶束增敏荧光光谱法测定恩诺沙星的含量[J].分析科学学报,2007,23(1):111-112.
[37]Ragab G H., Amin A S. Atomic absorption spectroscopic, conductometric and colorimetric methods for determination of fluoroquinolone antibiotics using ammonium reineckate ion-pair complex formation[J]. Spectrochim Acta, Part A 2004,60:973-978.
[38]Sun H W, Li L Q, Chen X Y. Investigation on sensitized chemiluminescence systems and their mechanism for five fluoroquinolones[J]. Anal. Chim Acta,2006,576:192-199.
[39]Mervartova K, Polasek M, Calatayud J M. Recent applications of flow-injection and sequential-injection analysis techniques to chemiluminescence determination of pharmaceuticals[J]. J Pharm Biomed Anal.,2007,45:367-381.
[40]Pearser W B, Gaydon A G. The identification of molecular spectra [M].4th Edition. London: Chapman & Hall,1976,297.
[41]Gao Y H, Sun X S, Sun Z J, Zhao N, Li Y R, Environ.Toxicol. Pharmacol.26 (2008) 177.
[42]Vancutsem P M, Babish J G, Schwark W S, Cornell Vet 80 (1990) 173.
[43]Aral F, Karacal F, Baba F, Research in Veterinary Science 84 (2008) 95.
[44]Fu L, Liu B Y, Shang J, Chinese Journal of Veterinary Drug,41 (05) (2007) 31.
[45]Jia L H, Ceng X D, Wang Q B, Guo X F, Chin. J Anal. Sci.23 (2007) 111.
[46]Gigosos P G, P R Revesado, Cadahia O, Fente C A, Vazquez B I, Franco C M, Cepeda A, J. Chromatogr. A 871 (2000) 31.
[47]National Pharmacopoeia Committee, China Pharmacopoeia, Beijing:Chemical Industry Publishing Company,2005
[48]Cinquina A L, Roberti P, Giannetti L, Longo F, Draisci R, Fagiolo A, Brizioli N R, J. Chromatogr. A 987 (2003)221.
[49]. Bimazubute M A, Rozet E, Dizier I, Gustin P, HubertP, Crommen J, Chiap P, J. Chromatogr. A 1189 (2008) 456.
[50]Mostafa S, El-Sadek M, Alla E A, Pharm J. Biomed. Anal.27 (2002) 133.
[51]Krebber R, Franz-Jurgen R, Ruttmann F, Anal. Chim. Acta, In Press,2008.
[52]Rodriguez E, Moreno-Bondi M C, Marazuela M D, ChromatogrJ. A 1209 (2008) 136.
[53]Chen J X, Xu F, Jiang H Y, Hou Y L, Rao Q X, Guo P J, Ding S Y. Food Chemistry 113 (2009) 1197.
[54]Zhang S X, Liu Z W, Zhou N Y, Wang Z H, Shen J Z. Anal. Chim.Acta 612 (2008) 83.
[55]Barron D, Jimenez-Lozano E, CanoJ, Barbosa J, J. Chromatogr. B 759 (2001) 73.
[56]Vargas Mamani M C, Amaya-Farfan J, Reyes Reyes F G, da Silva J A F, Rath S, Talanta 76 (2008) 1006.
[57]Kricka L J, Anal. Chim. Acta 500 (2003) 279.
[58]Adcock J L, Francis P S, Barnett N W, Anal. Chim. Acta 601(2007) 36.
[59]Mervartova K, Polasek M, Calatayud J M, Pharm J. Biom. Anal.45 (2007) 367.
[60]Zhou X M, Xing D, Zhu D B, Tang Y B, Jia L, Talanta 75 (2008) 1300.
[61]Sun H W, Wang F, Wen H F, Chen P Y, Analytical Laboratory,2008 in press.
[62]Shi H M, Shen S G, Sun H W, Liu Z F, Li L Q, J. Inorg. Biochem.101 (2007) 165.
[63]Sun H W, Hong H M, Shen S G, Kang W J, Guo Z F, Chin. J. Chem.26 (2008) 615.
[64]Blaikungeri A, Pelletier M, Monnier D, Inorg J. Chim. Acta 22 (1997) 7.
[65]Blikungeri A, Pelletier M, Inorg J. Chim. Acta 29 (1978) 141.
[66]Cui H, Zhang Z F, Shi M J, J. Phys. Chem. B 109 (2005) 3099.
[67]Liang S X, Zhao L X, Zhang B T, Lin J M, J. Phys. Chem. A 112 (2008) 618.
[68]Scholar E, Pharm X:The Comprehensive Pharmacology Reference,2008,1-5.
[69]Hennenberg M, Trebicka J, Buecher D, Sauerbruch T, Heller J, J. Hepatology 46 (Supplement 1) (2007) S82.
[70]Ni Y N, Wang Y, Kokot S, Spectrochim. Acta A 70 (2008) 1049.
[71]Tong C L, G HXiang, J. Fluoresc.16 (2006) 831.
[72]Sun H W, Xing T, Lian K Q, Internet Journal Chemistry,8 (8) (2006) 53.
[73]Huang K J, Liu X, Xie W Z, Yuan H W, Colloids and Surfaces B:Biointerfaces 64 (2008) 269.
[74]Mascher H J, Kikuta C, J. Chromatogr. A 812 (1998)381.
[75]Samanidou V F, Demetriou C E, Papadoyannis I N, Anal. Bioanal. Chem.375 (2003) 623.
[76]Rao R N, Nagaraju V, Pharm J.. Biomed.34 (2004) 1049.
[77]Lim J, Park B, Yun H, J.Chromatogr. B 772(2002) 185.
[78]Espinosa-Mansilla A, de la Pena A M, Gonzalez Gomez D, Salinas F, J. Chromatogr. B 822 (2005) 185.
[79]Kowalski C, Rolinski Z, Slawik Z, Glod B K, Liq J. Chromatogr. Relat. Technol.28 (2005) 121.
[80]Wan G H, Cui H, Pan Y L, Zheng P, Liu L J, J. Chromatogr. B 843 (2006) 1.
[81]Fierens C, Hillaert S, Vanden Bossche W J, J. Pharm. Biomed. Anal.22 (2000) 763.
[82]Alnajjar A, AbuSeada H H, Idris A M, Talanta 72(2007) 842.
[83]Alnajjar A, Idris A M, AbuSeada H H, J. Microchemical,87(2007) 35.
[84]Cheng C L, Fu C H, Chou C H, J. Chromatogr. B 856 (2007) 381.
[85]Yang Z J, Wang X L, Qin W D, Zhao H C, Anal. Chim. Acta 623, (2008) 231.
[86]Dodeigne C, Thunus L, Lejeune R, Talanta 51 (2000) 415.
[87]Kenichiro N, Bunseki Kagaku 49 (2000) 135.
[88]Kricka L J, Anal. Chim. Acta 500 (2003) 279.
[89]Navas M J, Jimenez A M, Food Chemistry 55 (1996) 7.
[90]Adcock J L, Francis P S, Barnett N W, Anal. Chim. Acta 601(2007) 36.
[91]Brown A J, Francis P S, Adcock J L, Lim K F, Barnett N W, Anal. Chim. Acta 624 (2008) 175.
[92]Lian N, Sun C Y, Zhao H C, Chin. J. Anal. Sci.18 (2002) 111.
[93]Liang Y D, Song J F, Yang H F, Anal. Chim. Acta 510 (2004) 21.
[94]Aly F A, Al-Tamimi S A, Alwarthan A A, Talanta 53 (2001) 885.
[95]Llorent Martinez E J, Garcia Reyes J F, Ortega Barrales P, Molina Diaz A, Anal. Chim. Acta 159 (2005) 532.
[96]He Y H, Lu J R, Zhang H G, Du J X, Microchim Acta 149 (2005) 239.
[97]Wang L, Yang P, Li Y X, Chen H Q, Li M G, Luo F B, Talanta,72 (2007) 1066.
[98]Liang Y D, Song J F, Yang X F, Anal. Chim. Acta 510 (2004) 21.
[99]Liao S L, Xie Z H. Spectroscopy and Spectral Analysis 25 (2005) 1938.
[100]Jeon C W, Khan M A, Lee S H, Karim M M, Lee H K, Suh Y S, Alam S M, Chung H F, J. Fluoresc.18(2008)843.
[101]Murillo J A, Alanon Molina A, de la Pena A M, Duran Meras I, Jimenez Giron A, J. Fluoresc.17 (2007)481.
[102]Sun H W, Li L Q, Chen X Y, Shi H M, Lv Y K, Can. J. Anal. Sci. Spectrosc.52 (2006) 100.
[103]Beltyukova S, Teslyuk O, Egorova A, Tselik E, J. Fluoresc.12 (2002) 269.
[104]Ma H Y, Zheng X W, Zhang Z J. Chin. J. Anal. Chem.32(2004) 857.
[105]Yao W, Wang L, Wang H Y, Zhang X L, Electrochim. Acta 54, (2008) 733.
[106]Shi H M, Shen S G, Sun H W, Liu Z F, Li L Q, J. Inorg. Biochem.101 (2007) 165.
[107]Shen S G, Shi H M, Sun H W, Huo S Y, Trans. Metal Chem.32 (2007) 167.
[108]Shen S G, Hong H M, Sun H W, Acta Physico-Chimica Sinica 23 (2007) 409.
[109]Sun H W, Hong H M, Shen S G, Kang W J, Guo Z F, Chin. J. Chem.26 (2008) 615.
[110]Cordoba-Borrego M, C6rdoba-Dz M, Cordoba-Diaz D. J. Pharm. Biomed. Anal.919 (1999) 18.