摘要
本论文共分为六个部分。对近二十年来用光度法检测药物进行了综述，按照药物的不同分析方法进行了分类，并分别讨论了它们的应用情况。
第一部分 本节对不同光度方法检测药物展开了评述，包括紫外-可见分光光度法、荧光光谱法、红外光谱分析法、磷光光谱法和核磁共振波谱法，并对化学计量学方法在该领域中的应用作了讨论。包括基于多元统计分析的模式识别法(主成分分析法、多元线性回归)，基于因子分析的多元校正方法(经典最小二乘法、主成分回归、偏最小二乘法和目标转换因子分析法)，基于生物遗传规律的神经网络算法，以及小波变换和遗传算法等。
第二部分 本节把多元校正方法用于甲硝唑、芬布芬和酮洛芬的测定，在pH7.0的KH_2PO_4-Na_2HPO_4缓冲溶液中对甲硝唑、芬布芬和酮洛芬三组分混合溶液进行了光度分析，所得的重叠光谱数据分别用经典最小二乘法(CLS)、主成分回归法(PCR)和偏最小二乘法(PLS)处理，并用于药片的测定，获得了较满意的结果。
第三部分 本节利用3-甲基苯骈噻唑啉-2-酮腙(MBTH)在硫酸介质和Fe(III)作用下催化氧化生成失电子和质子的产物，进而与吲哒帕胺和苯磺酸氨氯地平发生偶联反应，生成两种不同的蓝色化合物，进行了动力学分析。在优化的实验条件下对400-800nm之间的动力学数据、光谱数据和动力学-光谱数据进行了化学计量学方法解析。并采用加标回收法对鼠血清中吲哒帕胺和苯磺酸氨氯地平的含量进行了测定，结果令人满意。
第四部分 本节把化学计量学方法用于紫外-可见分光光度法中，在pH2.09的Britton-Robinson的缓冲溶液中测定了头孢呋辛钠、头孢曲松钠、头孢噻肟钠和头孢唑啉钠四组分，并通过加标回收法和高效液相色谱法测定了兔血清中四种β-内酰胺类头孢菌素的含量。结果较满意。
第五部分 本节在水溶液中对促凝血药氨甲苯酸和酚磺乙胺进行了分析，利用经典最小二乘法(CLS)、主成分回归法(PCR)和偏最小二乘法(PLS)等化学计量学方法进行了解析，并用高效液相色谱法对兔血清中的药物含量测定进行了对照，方法之间无显著性差异。
第六部分 本节在pH2.09的Britton-Robinson的缓冲溶液中测定了抗结核类药物异烟肼和吡嗪酰胺，对量测数据进行了化学计量学方法处理，并用于实际样品中的测定，结果令人满意。
The application of spectrometric techniques in pharmaceutical samples analysis has been developed. Chemometrics is a new discipline in chemistry that applied mathematical, statistical and other logic-based methods to analyze chemical data in particular in analytical chemistry. And the combination of spectrometry with chemometrics techniques can be used to solve some problem, which are countered in spectrum resolution.
This paper is divided into six parts:
Part I
This section has gathered most of the literatures that relate to spectrometry to application in the analysis of pharmaceutical multicomponent spectrometric determination. Including ultraviolet-visible spectrophotometry, fluorescence spectrophotometry, infrared absorption spectroscopy, phosphorescence spectrophotometry and nuclear magnetic resonance, et al. And the application of chemometrics in the analysis of pharmaceutical multicomponent spectrometric also be discussed. The chemometrics includes chemical experimental design and optimization (such as orthogonal design, simplex method and variance analysis), chemical pattern recognition (such as clusters, PCA, k-nearest neighbour analysis, SIMCA and ANN), multi-variance calibration (such as MLR, CLS, PCR and PLS) and spectrum analysis (such as ITTFA, EFA and FSWEFA), signal processing (such as filtering, smoothing, derivation and convolution). In the paper, for each category the experimental foundation and the situation of chemometrics' application in this field have been discussed. Including the sensitivity, linear range and chemometrics parameter.
Part II
In this section, metronidazole, fenbufen and ketoprofen have absorption at ultraviolet zone, and theirs absorption spectra are overlapping. So they can not be determined individually spectrophotometry without prior separation. In this paper , the chemometric multivariate calibration method was applied to the simultaneous determination of these three compounds in a potassium dihydrogen phosphate-sodium hydrogen phosphate buffer solution(pH7.0), and the analytical results was compared with classical least squares(CLS), principal components regression(PCR) and partial least squares(PLS). These methods were
sucessfully applied to the analysis of drugs with satisfied results.
Part III
In this section, A kinetic-spectrophotometric method has been developed for the simultaneous quantitative determination of Indapamide and Amlodipine besylate in rat serum. It relies on the different kinetic rates of the oxidative coupling reactions. The oxidative coupling reactions between 3-methylbenzothiazolin-2-one hydrazone (MBTH) and Indapamide and Amlodipine besylate, using
引文
[1] 南京药学院．药物分析．第一章，北京：人民卫生出版社，1980
[2] 焦更生．分光光度法在药物分析中的应用和发展．渭南师范学院学报，2004，19(1)：30-32
[3] 郑健，陈焕文，刘宏伟，李宝华，张寒琦，于爱民，金钦汉．紫外．可见分光光度法在药物分析中的应用．分析科学学报，2002，18(3)：158-163
[4] 崔宏杰，刘珍珍，吉爱国．紫外-可见微板分光光度法测定苯基环氧乙烷．理化检验-化学分册，2003，39(9)：554-555
[5] Chilukuri S.P. Sastry, Jana S.V.M. Lingeswara Rao. Determination ofdoxorubicin hydrochloride by visible spectrophotometry. Talanta, 1996, 43(11): 1827-1835
[6] Chilukuri S.P. Sastry, Petla Y. Naidu, Chilukuri S.R. Lakshmi, Manda N. Reddy, Ravi Chinthalapati. Application of sodium metaperiodate for the determination of ribavirin in pharmaceutical formulations. Talanta, 1998, 47(1): 85-93
[7] P. Ortega Barrales, M.L. Fernandez C6rdova, A. Molina Diaz. Indirect determination of ascorbic acid solid-phase spectrophotometry. Analytica Chimica Acta, 1998, 360(1): 143-152
[8] Julie Milano, Simone Goncalves Cardoso. Spectrophotometric determination of oxiconazole in topical lotion using methyl orange. Journal of Pharmaceutical and Biomedical Analysis, 2005, 37(4): 639-642
[9] Nafisur Rahman, Syed Najmul Hejaz Azmi. Spectrophotometric method for the determination of??verapamil hydrochloride in pharmaceutical formulations using N-bromosuccinimide as oxidant. IL FARMACO, 2004, 59(7): 529-536
[10] Abdulqawi Numan, Beata A. Musial, Neil D. Danielson. Spectrophotometric determination of diaminopyrimidines using benzoquinone. Journal of Pharmaceutical and Biomedical Analysis, 2002, 30(3): 761-771
[11] Chilukuri S.P. Sastry, Ravi Chintalapati, Adapa V.S.S. Prasad, Bhetanabhotla S. Sastry. Application of oxidative coupling reactions for the estimation of ritodrine hydrochloride in bulk sample and dosage forms. TaIanta, 2001, 53(5): 907-914
[12] K. Basavaiah, P. Nagegowda. Determination of ranitidine hydrochloride in pharmaceutical preparations by titrimetry and visible spectrophotometry using bromate and acid dyes. IL FARMACO, 2004, 59(2): 147-153
[13] Nafisur Rahman, Manisha Singh, Md. Nasrul Hoda. Application of oxidants to the spectrophotometric determination of amlodipine besylate in pharmaceutical formulations. IL FARMACO, 2004, 59(11): 913-919
[14] A. Ruiz Medina, M.L. Fernandez de C6rdova, A. Molina Diaz. A rapid and selective solid-phase UV spectrophotometric method for determination of ascorbic acid in pharmaceutical preparations and urine. Journal of Pharmaceutical and Biomedical Analysis, 1999, 20(3): 247-254
[15] 王绪明，朱宝玉，尹川．导数光谱法在药物分析中的应用进展．解放军药学学报，2000，16(5)：258-262
[16] Saeide Altinoz, Ozen Ozcan Dursun. Determination of nimesulide in pharmaceutical dosage forms by second order derivative UV spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 2000, 22(1): 175-182
[17] N. Karasen, S. Altinoz. Determination of mirtazapine in tablets by UV spectrophotometric and derivative spectrophotometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2000, 24(1): 11-17
[18] J. Hanaee. Simultaneous determination of acetaminophen and codeine in pharmaceutical preparations by derivative spectrophotometry. PharmaceuticaActa Helvetiae, 1997, 72(4): 239-241
[19] Nuran Ozaltin. Determination of Lansoprazole in pharmaceutical dosage forms by two different spectroscopic methods. Journal of Pharmaeesitcal and (?)edical(?)ysis, 1999, 20(3): 599-606
[20] Zafer Dinner, Hasan Basan, Nilgun Gunden Goger. Quantitative determination of ambroxol in tablets by derivative UV spectrophotometrie method and HPLC. Journal of Pharmaceutical and Biomedical Analysis, 2003, 31(5): 867-872
[21] Zenon Kokot, Kinga Burda. Simultaneous determination of salicylic acid and acetylsalicylic acid in aspirin delayed-release tablet formulations by second-derivative UV spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 1998, 18(4-5): 871-875
[22] Sacide Altinoz, Dilara Tekeli. Analysis of glimepiride by using derivative UV speetrophotometric method. Journal of Pharmaceutical and Biomedical Analysis, 2001, 24(3): 507-515
[23] Nevin Erk. Rapid and simple methods for quantitative analysis of some antidepressant in??pharmaceutical formulations by using first derivative spectrophotometry and HPLC. II Farmaco, 2003, 58(12): 1209-1216
[24] E.M. Hassan, M.E.M. Hagga, H.I. Al Johar. Determination of cisapride in pharmaceutical preparations using derivative spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 2001, 24(4):659-665
[25] T.G. Altuntas, S.S. Zanooz, D. Nebioglu. Quantitative determination of acrivastine and pseudoephedrine hydrochloride in pharmaceutical formulation by high performance liquid chromatography and derivative spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 1998,17(2): 103-109
[26] Saadet Gungor, Feyyaz Onur. Determination of astemizole in pharmaceutical preparations using spectrophotometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2001, 25(3): 511-521
[27] incilay Suslu, Sacide Altmoz. Two derivative spectrophotometric determinations of indapamide in pharmaceutical dosage forms. Journal of Pharmaceutical and Biomedical Analysis, 2002, 30(2): 357-364
[28] T. Radhakrishna, A. Narasaraju, M. Ramakrishna, A. Satyanarayana. Simultaneous determination of montelukast and loratadine by HPLC and derivative spectrophotometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2003,31(2): 359-368
[29] Valentina Marinkovic, Danica Agbaba, Katarina Karljikovic-Rajic, Jozef Comor, Dobrila Zivanov-Stakic. UV derivative spectrophotometric study of the photochemical degradation of nisoldipine. II Farmaco, 2000, 55(2): 128-133
[30] Durisehvar Ozer, Hulya Senel. Determination of lisinopril from pharmaceutical preparations by derivative UV spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 1999, 21(3): 691-695
[31] M.J. Lopez de Alda, P. Paseiro, A.G Goicoechea. Rapid zero-order and second-derivative UV spectrophotometric determination of cyanocobalamin in pharmaceutical formulations containing dextran and preservatives. Journal of Pharmaceutical and Biomedical Analysis, 1996, 14(6): 363-365
[32] Milena Jelikic-Stankov, Jadranka Odovic, Dejan Stankov, Predrag Djurdjevic. Determination of fleroxacin in human serum and in dosage forms by derivative UV spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 1998, 18(1): 145-150
[33] K. Karljikovic-Rajic, D. Novovic, V. Marinkovic, D. Agbaba. First-order UV-derivative spectrophotometry in the analysis of omeprazole and pantoprazole sodium salt and corresponding impurities. Journal of Pharmaceutical and Biomedical Analysis, 2003,32(4-5): 1019-1027
[34] Bilal Yilmaz, Murat Ozturk, Yucel (Yasar) Kad(?)oglu. Comparison of two derivative spectrophotometric methods for the determination of α-tocopherol in pharmaceutical preparations. II FARMACO, 2004, 59(5): 723-727
[35] Alaa El-Gindy, Abdel Fattah M. El Walily, Mohamed F. Bedair. First-derivative spectrophotometric and LC determination of cefuroxime and cefadroxil in urine. Journal of Pharmaceutical and??BiomedicalAnalysis, 2000, 23(2): 341-352
[36] Nevin Erk. Application of derivative-differential UV spectrophotometry and ratio derivative spectrophotometric determination of mephenoxalone and acetaminophen in combined tablet preparation. Journal of Pharmaceutical and Biomedical Analysis, 1999, 21(2): 429-437
[37] Murat Kartal, Nevin Erk. Simultaneous determination of hydrochlorothiazide and amiloride hydrochloride by ratio spectra derivative spectrophotometry and high-performance liquid chromatography. Journal of Pharmaceutical and Biomedical AnaIysis, 1999, 19(3): 477-485
[38] Alaa EI-Gindy, Samy Emara, Ghada M. Hadad. Spectrophotometric and liquid chromatographic determination of trimebutine maleate in the presence of its degradation products. Journal of Pharmaceutical and Biomedical Analysis, 2003, 33 (2): 231-241
[39] Nevin Erk, Murat Kartal. Simultaneous high performance liquid chromatographic and derivative ratio spectra spectrophotometry determination of chlorpheniramine maleate and phenylephrine hydrochloride. H Farmaco, 1998, 53(8): 617-622
[40] Nevin Erk. Quantitative analysis of chlorpheniramine maleate and phenylephrine hydroehioride in nasal drops by differential-derivative spectrophotometric, zero-crossing first derivative UV spectrophotometric and absorbance ratio methods. Journal of Pharmaceutical and Biomedical Analysis, 2000, 23(10): 1023-1031
[41] Yasser S. EI-Saharty, Nagiba Y. Hassan, Fadia H. Metwally. Simultaneous determination of terbinafine HCL and triamcinolone acetonide by UV derivative speetrophotometry and spectrodensitometry. Journal of Pharmaceutical and Biomedical Analysis, 2002, 28(3): 569-580
[42] 黄朝表，陈恒武，何巧红．流动注射在线光化学荧光法测定药物制剂中叶酸的含量．分析化学，2003，31(2)：229-231
[43] 曹晓霞，陈恒武，何巧红．扑热息痛的光化学荧光特性及其分析应用．分析化学，2000，28(4)：491-493
[44] 白鹤松．氢化物——原子荧光法测定藏药中的砷汞．赢海师专学报，2000，6(2)：70-72
[45] 邝荔香，鲁义东，程钢，方惠敏，赵祥大．荧光光度法测定结核清血药浓度．中国临床药学杂志，1999，8(1)：44-45
[46] Toshimasa Toyo'oka, Ayako Suzuki, Takeshi Fukushima, Masaru Kato. Hair analysis of histamine after fluorescence labeling by column-switching reversed-phase liquid chromatography with electrospray ionization mass spectrometry and application to human hair. Analytical Biochemistry, 2004, 333(2): 236-245
[47] I. I. Hewala. Speetrofluorimetrie and derivative absoption spectrophotometric techniques for the determination of loperamide hydrochloride in pharmaceutical formulations. Journal of Pharmaceutical & BiomedicalAnalysis, 1995, 13(9): 761-767
[48] Suzy M. Sabry, Mohamed H. Abdel-Hay, Magda H. Barary, Tarek S. Belal. Sensitive spectrofluorimetrie and spectrophotometric methods for the determination of thonzylamine hydrochloride in pharmaceutical preparations based on coupling with dimethylbarbituric acid in presence of dicyclohexylearbodiimide. Journal of Pharmaceutical and BiomedicalAnalysis, 2000,??22(2): 257-264
[49] Heba H. Abdine, Azza A. Gazy, Moharned H. Abdel-Hay. Simultaneous determination of melatonin-pyridoxine combination in tablets by zero-crossing derivative spectrophotometry and spectrofluorimetry. Journal of Pharmaceutical and Biomedical Analysis, 1998, 17(3): 379-386
[50] Omayma Abdel Razak.Fluorimetric and spectrophotometric determination of ritodrine hydrochloride in bulk and pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis, 1998, 18(3): 359-365
[51] Aiaa EI-Gindy, Ahmed Ashour, Laila Abdel-Fattah, Marwan M. Shabana. Spectrophotometric, septrofluorimetric and LC determination of lisinoprii. Journal of Pharmaceutical and Biomedical Analysis, 2001, 25(5): 913-922
[52] Alaa El-Gindy, Badr E1-Zeany, Tamer Awad, Marwan M. Shabana. Spectrophotometric, spectrofluorimetrie and LC determination oftrazodone hydrochloride. Journal of Pharmaceutical and Biomedical Analysis, 2001, 26(2): 211-217
[53] Abdel Fattah M. El Walily, Saeid F. Belal, Rania S. Bakry. Spectrophotometric and spectrofluorimetric estimaton of ciprofloxacin and norfloxacin by ternary complex formation with eosin and palladium(Ⅱ). Journal of Pharmaceutical and Biomedical Analysis, 1996, 14(5): 561-569
[54] Suzy M. Sabry, Essam F. Khamis. Application of H-point standard additions method to spectrophotometric and spectrofluorimetric determinations of glafenine and glafenic acid in mixtures. Talanta, 2000, 51(10): 1219-1231
[55] Suzy M. Sabry, Hoda Mahgoub. Voltammetric, spectrofluorimetric and spectrophotometric methods to determine flufenamic acid. Journal of Pharmaceutical and Biomedical Analysis, 1999, 21 (5): 993-1001
[56] Hoda Mahgoub. Spectrophotometrie and fluorimetric determination of aztreonam in bulk and dosage forms. Journal of Pharmaceutical and Biomedical Analysis, 2003, 31 (4): 767-774
[57] Ekram M. Hassan. Spectrophotometric and fluorimetric methods for the determination of meloxicam in dosage forms. Journal of Pharmaceutical and Biomedical Analysis, 2002, 27(5): 771-777
[58] Mostafa A. Shehata, Nagiba Y. Hassan, Ahmad S. Fayed, Badr A. El-Zeany. Derivative spectrophotometric and fluorimetric methods for determination of rofecoxib in tablets and in human plasma in presence of its photo-degradation product. IL FARMACO, 2004, 59(2): 139-145
[59] Nevin Olgun, Sidika Erturk, SedefAtmaca. Spectrofluorimetric and spectrophotometric methods for the determination of vigabatrin in tablets. Journal of Pharmaceutical and Biomedical Analysis, 2002, 29(1-2): 1-5
[60] 艾军，李蕾，熊军．傅立叶变换红外光谱法测定胆结石中胆固醇含量．分析化学，1999，27(9)：742
[61] 刘凤萍，吴湘江，吴婷．青霉素类药物的红外光谱鉴别．光谱实验室，2004，21(1)：131-134
[62] Ilyana Karamancheva, Tinka Staneva. Determination of possible impurities in piracetam using FTIR spectroscopy. Journal of Pharmaceutical and Biomedical Analysis, 2000, 21(6): 1161-1169
[63] 张海容．室温磷光化学传感器研究进展．忻州师院学报，2000，16(1)：25-43
[64] 胡敏，胡昌勤，刘文英．核磁共振波谱法测定药物基准物质的绝对含量．分析化学，2004，32(4)：??451-455
[65] Seref Demirayak, Omit Ucucu, Kadriye Benkli, Nalan Gundogdu-Karaburun, Ahmet Cagrl Karaburun, Derya Akar, Muhammed Karabacak, Nuri Kiraz. Synthesis and antifungal activities of some aryl(benzofunran-2-yl)ketoximes. IL Farmaco, 2002, 57(6): 609-612
[66] Thomas Mavromoustakos, Maria Zervou, Dimitris Panagiotopoulos, Efthimia Theodoropoulou, John Matsoukas, Dimitrios Karussis. Structural elucidation and conformational properties of the immunomodulator.linomide. Journal of Pharmaceutical and Biomedical Analysis, 1998, 16(5): 741-751
[67] Anne Kruse Lykkeberg, Gitte Sengelov, Claus Comett, Jette Tjomelund, Steen Honore Hansen, Bent Halling-Sorensen. Isolation, structural elucidation and in vitro activity of 2-acetyl-2-decarboxamido-oxytetracycline against environmental relevant bacteria, including tetracycline-resistant bacteria. Journal of Pharmaceutical and BiomedicaI Analysis, 2004, 34(3): 559-567
[68] Ariana Zoppi, Marcela Linares, Marcela Long, hi. Quantitative analysis of enalapril by ~1H NMR spectroscopy in tablets. Journal of Pharmaceutical and Biomedical Analysis, 2005, 37(6): 627-630
[69] Zahra Talebpour, Soheila Haghgoo, Mojtaba Shamsipur. ~1H nuclear magnetic resonance spectroscopy analysis for simultaneous determination of levodopa, carbidopa and methyldopa in human serum and pharmaceutical formulations. Analytica Chimica Acta, 2004, 506(1): 97-104
[70] Sabry Khalil, Ahmed Kelzieh. Determination of veraparnil in pharmaceutical formulations using atomic emission spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 2002, 27(1-2): 123-131
[71] S. Khalil, M.A. EI-Ries. AAS and AES determination of furaltadone, methadone and trazodone in pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis, 2002, 27(1-2): 117-122
[72] Krystyna Soltyk, Anna Lozak, peter Ostapczuk, Zbigniew Fijalek. Determination of chromium and selected elements in multimineral and multivitamin preparations and in pharmaceutical raw material. Journal of Pharmaceutical andBiomedicaIAnalysis, 2003, 32(3): 425-432
[73] 程翼宇，陈闽军，钟建毅．Daubechies小波主成分回归法机理及算法研究．化学学报，1999， 57(12)：1352-1358
[74] 颜杰，丁德荣，刘世庆．小波变换-偏最小二乘算法及其在复方甲硝唑注射液分析中的应用．分析测试学报，2000，19(1)：71-73
[75] 刘世庆，兰梦宁，王玮雯，代莉飞．迭代目标转换因子分析法测定多组分复方药物制剂的研究．沈阳药科大学学报，1998，15(2)：167-171
[76] 王燕，陈国松，王镇浦．化学计量学辅助紫外分光光度法同时测定小儿复方苯巴比妥片剂中四组分的研究．分析实验室，2000，19(5)：27-30
[77] 王煜，刘世庆，马恩龙，李艳春．偏最小二乘法-BP神经网络用于多组分药物测定．分析实验室，2000，19(4)：34-36
[78] 刘培义，任玉林，苟玉慧，郭晔，王宗睦，汤真，田丽容，杜玉荣．人工神经网络-近红外光谱法用??于甲氧苄胺嘧啶粉末药品的非破坏定量分析．高等学校化学学报，2000，21(4)：544-546
[79] 严拯宇，王朝晖，姜新民，张圣华．人工神经网络应用于光谱分析同时测定增效联磺片三组分含量．分析科学学报，1999，15(4)：297-301
[80] 侯廷军，徐筱杰．遗传算法在计算机辅助药物分子设计中的应用．化学进展，2004，16(1)：35-41
[81] 孙亮．遗传算法在放射性药物内照射生物动力学数据分析中的应用．苏州大学学报(医学版)，2004，24(5)：661-664
[82] Abdel-Aziz M. Wahbi, Omayma Abdel-Razak, Azza A. Gazy, Hoda Mahgoub, Marwa S. Moneeb. Speetrophotometric determination of omeprazole, lansoprazole and pantoprazole in pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis, 2002, 30(4): 1133-1142
[83] I. Duran Meras, A. Espinosa Mansilla, F. Salinas L6pez, M.J. Rodr/guez G6mez. Determination of triamterene and leucovorin in biological fluids by UV derivative-spectrophotometry and partial least-squares (PLS-1) calibration. Journal of Pharmaceutical and Biomedical Analysis, 2002, 27(1-2): 81-90
[84] A. Ruiz Medina, M.L. Fernandez de Cordova, A. Molina-Diaz.Simultaneous determination of paracetamol, caffeine and acetylsalicylic acid by means of a FI ultraviolet pls multioptosensing device. Journal of Pharmaceutical and Biomedical Analysis, 1999, 21(7): 983-992
[85] Marcelo M. Sena, Zahra F. Chaudhry, Carol H. Collins, Rohei J. Poppi. Direct determination of diclofenac in pharmaceutical formulations containing B vitamins by using UV spectrophotometry and partial least squares regression. Journal of Pharmaceutical and Biomedical Analysis, 2004, 36(4): 743-749
[86] Erdal Dinc, Ozgur Usundag. Chemometric resolution of a mixture containing hydrochlorothiazide and amiloride by absorption and derivative spectrophotometry. Journal of Pharmaceutical and Biomedical Analysis, 2002, 29(1-2): 371-379
[87] Erdal Ding, Cem Yucesoy, I. Murat Palablylk, Ozgur Ustundag, Feyyaz Onur. Simultaneous spectrophotometric determination of cyproterone acetate and estradiol valerate in pharmaceutical preparations by ratio spectra derivative and chemometric methods, Journal of Pharmaceutical and Biomedical Analysis, 2003, 32(3): 539-547
[88] Erdal Ding, Cem Yueesoy, Feyyaz Onur. Simultaneous speetrophotometric determination of mefenamic acid and paracetamol in a pharmaceutical preparation using ratio spectra derivative spectrophotometry and ehemometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2002, 28(6): 1091-1100
[89] Erdal Ding, I. Murat Palablylk, Ozgur Ustundag, Filiz Yurtsever, Feyyaz Onur. Simultaneous spectrophotometric determination of chlorphenoxamine hydrochloride and caffeine in a pharmaceutical preparation using first derivative of the ratio spectra and chemometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2002, 28(3): 591-600
[90] E. Ding, C. Serin, F. Tugcu-Demiroz, T. Doganay. Dissolution and assaying of multicomponent tablets by chemometric methods using comuputer-aided spectrophotometer. International Journal of Pharmaceutics, 2003, 250(2):339-350[91] Erdal Ding, Ozgur Ustundag. Spectrohotometric quantitative resolution of hydrochlorothiazide and spironolactone in tablets by chemometric analysis methods. IL Farmaco, 2003, 58(6): 1151-1161
[92] Erdal Ding,Dumitru Baleanu. Spectrophotometrie quantitative determination of eilazapril and hydrochlorothiazide in tablets by chemometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2002, 30(3): 715-723
[93] Alaa El-Gindy, Ahmed Ashour, Laila Abdel-Fattah, Marwan M. Shabana. Spectrophotometric determination of benazepril hydrochloride and hydrochlorothiazide in binary mixture using second derivative, second derivative of the ratio spectra and chemometric methods. Journal of Pharmaceutical and Biomedical Analysis, 2001, 25(2): 299-307
[94] Alaa El-Gindy, Samy Emara, Ahmed Mostafa. HPLC and chemometric-assisted spectrophotometric methods for simultaneous determination of atenolol, amiloride hudrochloride and chiorthalidone. IL Farmaco 2005, 60(2): 269-278
[95] Alaa El-Gindy, Fawzy El-Yazby, Ahmed Mostafa, Moustafa M. Maher. HPLC and chemometric methods for the simultaneous determination of cyproheptadine hydrochloride, multivitamins, and sorbic acid. Journal of Pharmaceutical and Biomedical Analysis, 2004, 35(4): 703-713
[96] Alaa El-Gindy, Ahmed Ashour, Laila Abdel-Fattah, Marwan M. Shabana. Spectrophotometric and HPTLC-densitometric determination of lisinopril and hydrochlorothiazide in binary mixtures. Journal of Pharmaceutical and Biomedical Analysis, 2001, 25(5): 923-931
[97] L.F. Capitan-Vallvey, N. Navas, M. del Olmo, V. Consonni, R. Todeschini. Resolution of mixtures of three nonsteroidal anti-inflammatory drugs by fluorescence using partial least squares multivariate calibration with previous wavelength selection by Kohonen artificial neural networks. Talanta, 2000, 52(6): 1069-1079
[98] Yongnian Ni, Chao Liu, Serge Kokot. Simultaneous kinetic spectrophotometric determination of acetaminophen and Phenobarbital by artificial neural networks and partial least squares. Analytica Chimica Acta, 2000, 419(2): 185-196
[99] Sayo O. Fakayode, Isabel M. Swamidoss, Marianna A. Busch, Kenneth W. Busch. Determination of the enantiometric composition of some molecules of pharmaceutical interest by chemometric analysis of the UV spectra of guest-host eomplexs formed with modified cyclodextrins. Talanta 65(2005) 838-845
[100] 中国药学会药物分析专业委员会．药物分析进展概述．中国药学杂志，1997，32(11)：12-15
[101] 汪尔康。21世纪分析化学．北京：科学出版社，1999年
[102] 陆晓华．化学计量学．武汉：华中理工大学出版社，1997[1] T. Saffaj, M. Charrouf, A. Abourrichc, Y. Abboud, A. Bennamara, M. Berrada. Spectrophotometric determination of metronidazole and secnidazole in pharmaceutical preparations. IL FARMACO, 2004, 59(10): S43-S46.
[2] A. Van Overbeke, W. Baeyens, W. Van den Bossehe. Quantitative Fourier transform infrared/attenuated total reflectance analysis of ketoprofcn in some pharmaceutical formulations. Vibrational Spectroscopy, 1995, 9(2): 121-130.[3] Ticiano Gomes do Nascimento, Eduardo de Jesus Oliveira, Rui Oliveira Macedo. Simultaneous determination of ranitidine and metronidazole in human plasma using high performance liquid chromatography with diode array detection. Journal of Pharmaceutical and Biomedical Analysis, 2005, 37(4): 777-783.
[4] Toshio Hirai, Shozo Matsumoto, Ikuo Kishi. Simultanous analysis of several non-steroidal anti- inflammatory drugs in urine by high-performance liquid chromatography with normal solid-phase extraction. Journal of Chromatography B, 1997, 692(2): 375-388
[5] E.G. de Jalon, M. Josa, M.A. Campanero, S. Santoyo, P. Ygartua. Determination by high-performance liquid chromatography of ketoprofen in vitro in rat skin permeation samples. Journal of Chromatography A, 2000, 870(1-2): 143-149
[6] P.N. Bartlett, E. Ghoneim, G. El-Hefnawy, I. El-Hallag. Voltammetry and determination of metronidazole at a carbon fiber microdisk electrode. Talanta, 2005, 66(4): 869-874
[7] Orhan Cakirer, Esma Kihc, Orhan Atakol, Adnan Kenar. The non-aqueous titrimetric assay of the selected anti-inflammatory agents using tetra-n-butylammonium hydroxide as titrant. Journal of Pharmaceutical and Biomedical Analysis, 1999,20(1-2): 19-26
[8] M. Angeles Herrador, A. Gustavo Gonzalez. Potentiometric titrations in acetonitrile-water mixtures: evaluation of aqueous ionization constant of ketoprofen. Talanta, 2002, 56(4): 769-775.
[9] M. Palomeque, J.A. Garcia Bautista, J.V. Garcia Mateo, J. Martinez Calatayud. Flow injection biamperometric determination of metronidazole with on-line photodegradation. Analytica Chimica Acta, 1999,401(2): 229-236
[10] Hassan Y. Aboul-Enein, Arin Gul Dal, Muzaffer Tuncel. A validated method development for ketoprofen by a flow-injection analysis with UV-detection and its application to pharmaceutical formulation. II Farmaco, 2003, 58(6): 419-422.
[11] Franciszek K. Glowka. Determination of ketoprofen enantiomers in human serum by capillary zone electrophoresis: man pharmacokinetic studies after administration of rac-ketoprofen tablets. Journal of Pharmaceutical and Biomedical Analysis, 2002, 30(4): 1035-1045[1] Nevin Erk. Comparison of spectrophotometric and an LC method for the determination perindopril and indapamide in pharmaceutical formulations. Journal of pharmaceutical and Biomedical Analysis, 2001,26(1):43-52.
[2] Incilay Suslu, Sacide Altmoz. Two derivative spectrophotometric determination of indapamide in pharmaceutical dosage forms. Journal of pharmaceutical and Biomedical Analysis, 2002, 30(2): 357- 364.
[3] Alaa El-Gindy, Samy Emara, Ghada M. Hadad. Determination of certain drugs in binary mixtures formulations by second derivative ratio spectrophotometry and LC. II. FARMACO, 2004, 59(9): 703- 712.
[4] Nafisur Rahman, Md. Nasrul Hoda. Validated spectrophotometric methods for the determination of amlodipine besylate in drug formulations using 2,3-dichloro 5,6-dicyano 1,4-benzoquinone and ascorbic acid. Journal of pharmaceutical and Biomedical Analysis, 2003, 31(2): 381-392.
[5] Nafisur Rahman, Manisha Singh, Md. Nasrul Hoda. Application of oxidants to the spectrophotometric determination of amlodipine besylate in pharmaceutical formulations. II.FARMACO, 2004, 59(11): 913-919.
[6] Nafisur Rahman, Syed Najmul Hejaz Azmi. Spectrophotometric method for the determination of amlodipine besylate with ninhydrin in drug formulations. II.FARMACO, 2001, 56(10): 731-735
[7] K. Basavaiah, U. Chandrashekar, H.C. Prameela. Sensitive spectrophotometric determination of amlodipine and felodipine using iron(III) and ferricyanide. II.FARMACO, 2003, 58(2): 141-148.
[8] Dragica Zendelovska, Trajce Stafilov, Marina Stefova. Optimization of a solid-phase extraction method for determination of indapamide in biological fluids using high-performance liquid chromatography. Journal of Chromatography B, 2003, 788(1): 199-206.
[9] Florin Albu, Cristina Georgita, Victor David, Andrei Medvedovici. Liquid chromatography- electrospray tandem mass spectrometry method for determination of indapamide in serum for single/multiple dose bioequivalence studies of sustained release formulations. Journal of Chromatography B, 2005, 816(1-2): 35-40.
[10] A. Radi. Stripping voltammetric determination of indapamide in serum at castor oil-based carbon paste electrodes. Journal of pharmaceutical and Biomedical Analysis, 2001, 24(3): 413-419.
[11] Azza Abdel Kader Gazy. Determination of amlodipine besylate by adsorptive square-wave anodic stripping voltammetry on glassy carbon electrode in tablets and biological fluids. Talanta, 2004, 62(3): 575-582.
[12] Zhouping Wang, Zhujun Zhang, Xiao Zhang, Zhifeng Fu. Flow-injection inhibition chemiluminescence determination of indapamide based on luminol-ferricyanide reaction. Journal of pharmaceutical and Biomedical Analysis, 2004, 35(1): 1-7.
[13] M.G. Quaglia, F. Barbato, S. Fanali, E. Santucci, E. Donati, M. Carafa, C. Marianecci. Direct determination by capillary electrophoresis of cardiovascular drugs, previously included in liposomes. Journal of pharmaceutical and Biomedical Analysis, 2005, 37(1): 73-79.[14]N.A. El Ragehy, S.S. Abbas, S.Z. El-Khateeb. Stability indicating method for determination of nortriptyline hydrochloride using 3-methyl-2-benzothiazolinone hydrazone(MBTH). Journal of pharmaceutical and Biomedical Analysis, 2001, 25(1): 143-151.
[15]Nafisur Rahman, Nadeem Ahmad Khan, Syed Najmul Hejaz Azmi. Optimized and validated spectrophotometric methods for the determination of nicorandil in drug formulations and biological fluids. II.FARMACO, 2004, 59(7): 519-527
[16] Chiluk uri S.P. Sastry, Ravi Chintalapati, Adapa V.S.S. Prasad, Bhetanabhotla S. Sastry. Application of oxidative coupling reactions for the estimation of ritodrine hydrochloride in bulk sample and dosage forms. Talanta, 2001, 53(5): 907-914.
[17] P. Nagaraja, R.A. Vasantha, H.S. Yathirajan. Spectrophotometric methods for the rapid determination of menadione and menadione sodium bisulphate and their application in pharmaceutical preparations. Journal of Pharmaceutical and Biomedical Analysis, 2002, 28(2): 161-168.
[18] P. Nagaraja, K.R. Sunitha, R.A. Vasantha, H.S. Yathirajan. Spectrophotometric determination of metronidazole and tinidazole in pharmaceutical preparations. Journal of Pharmaceutical and Biomedical Analysis, 2002,28(3): 527-535.
[19] K. Sreedhar, C.S.P. Sastry, M. Narayana Reddy, D.G. Sankar. Spectrophotometric methods for the determination of prazosin hydrochloride in tablets. Talanta, 1996,43(11): 1847-1855.
[20] Fawzy A. El-Yazbi, Heba H. Abdine, Rasha A. Shaalan. Spectrophotometric methods for the determination of benazepril hydrochloride in its single and multi-component dosage forms. Journal of Pharmaceutical and Biomedical Analysis, 1999, 20(1): 343-350.
[21] M. Sultan. Spectrophotometric determination of acyclovir in some pharmaceutical formulations. II. FARMACO, 2003, 57(11): 865-870.
[22] Chilukuri S.P. Sastry, Petla Yerrayya Naidu, S.S.N. Murty. Spectrophotometric methods for the determination of omeprazole in bulk form and pharmaceutical formulations. Talanta, 1997, 44(7): 1211-1217.
[23] M. Soledad Garcia, M. Isabel Albero, Concepcion Sanchez-Pedreno, Jose Molina. Flow-injection spectrophotometric determination of dicolfenac sodium in pharmaceuticals and urine samples. Journal of Pharmaceutical and Biomedical Analysis, 1998, 17(2): 267-273.
[24] Rui A.S. Lapa, Jose L.F.C. Lima, Joao L.M. Santos. Dual-stopped-flow spectrophotometric determination of amiloride hydrochloride in a multicommutated flow system. Analytica Chimica Acta, 2000, 407(1): 225-231.
[25] Ali A. El-Emam, Fathalla F. Belal, Mohamed A. Moustafa, Saadia M. El-Ashry, Dina T. El-Sherbiny, Steen Honore Hansen. Spectrophotometric determination of propranolol in formulations via oxidative coupling with 3-methylbenzothiazoline-2-one hydrazone. II.FARMACO, 2003, 58(11): 1179-1186.
[26] Adapa V.S.S. Prasad, Chilukuri S.R. Lakshmi, Chilukuri S.P. Sastry, Viplava P. Uppuleti. Determination of minocycline by oxidative coupling and diazocoupling reactions in pharmaceutical formulations. Journal of Pharmaceutical and Biomedical Analysis, 2002, 30(3): 491-498.[27] Ana C.B. Dias, Joao L.M. Santos, Jose L.F.C. Lima, Elias A.G. Zagatto. Multi-pumping flow system for spectrophotometric determination of bromhexine. Analytica Chimica Acta, 2003, 499(1): 107-113.
[28] Mari a Lopez Carreto, Loreto Lunar, Soledad Rubio, Dolores Perez-Bendito. Simultaneous spectrophotometrie determination of chlorpromazine, perphenazine and acetopromazine by use of the kinetic wavelength pair-method. Analytica Chimica Acta, 1997, 349(1): 33-42.
[29] Yongnian Ni, Chao Liu, Serge Kokot. Simultaneous kinetic spectrophotometric determination of acetaminophen and Phenobarbital by artificial neural networks and partial least squares. Analytica Chiraica Acta, 2000, 419(2): 185-196.
[30] 倪永年，刘超．动力学光度法同时测定苯巴比妥与扑热息痛．福州大学学报(自然科学版．1999，27(增刊)：212-213
[31] Takashi Tomiyasu, Norinobu Yonehara, Norio Teshima, Takuji Kawashima. Kinetic method for the determination of iron(Ⅱ, Ⅲ) by its catalytic effect on the oxidation of 3-methyl-2benzothiazolinone hydrazone with hydrogen peroxide. Analytica Chimica Acta, 1999, 394(1): 55-63
[32] 倪永年。化学计量学在分析化学中的应用[M]．北京：科学出版社，2004．[1] Magda M. Ayad, Abdalla A. Shalaby, Hisham E. Abdellatef, Heba M. Elsaid. Spectrophotometric and atomic absorption spectrometric determination of certain cephalosporins. Journal of Pharmaceutical and Biomedical Analysis, 1999, 18(6): 975-983.
[2] Alaa S. Amin, Gamal H. Ragab. Spectrophotometric determination of certain cephalosporins in pure form and in pharmaceutical formulations. Spectrochimica Acta Part A, 2004, 60 (12): 2831-2835.
[3] Alaa El-Gindy, Abdcl Fattah M. El Walily, Mohamed E Bedair. First-derivative spcetrophotometric and LC determination of cefuroxime and cefadroxil in urine. Journal of Pharmaceutical and Biomedical Analysis, 2000, 23 (2): 341-352.
[4] 赫春香，张淑玢，张淑敏，金学迎，汪秀龄．头孢噻肟钠的极谱伏安行为及其单扫描示波极谱法测定．分析试验室，1999，18(2)：15-19
[5] Genowefa Pajehel, Stefan Tyski. Adaptation of capillary electrophoresis to the determination of selected cephalosporins for injection. Journal of Chromatography A, 2000, 895 (1-2): 27-31.
[6] Lories I. Bebawy, Khadiga El Kelani, Laila Abdel Fattah. Fluorimetric determination of some antibiotics in raw material and dosage forms through ternary complex formation with terbium(Tb~(3+)). Journal of Pharmaceutical and Biomedical Analysis, 2003, 32 (6): 1219-1225.
[7] P. Sharma, H.P.S Chawla, R. Panchagnula. LC determination of cephalosporins in in vitro rat intestinal sac absorption model. Journal of Pharmaceutical and Biomedical Analysis, 2002, 27 (1-2): 39-50.
[8] 倪永年．化学计量学在分析化学中的应用[M]，北京：科学出版社，2004：134．
[9] 吴根华，何池洋，陈荣．人工神经网络用于荧光分析法同时测定苯酚和间苯二酚的含量．光谱学与光谱分析，2002，22(5)：813-815．[1] 陈新谦，金有豫．新编药物学[M]．第14版．北京：人民卫生出版社，1998：390．
[2] 伦新强．氨甲苯酸与酚磺乙胺配伍的稳定性．中国医院药学杂志，2001，21(12)：761-762．
[3] Elazazy M S, Shalaby A, Elbolkiny M N, Khalil H M. Speetrophotometric determination of aciclovir, cefepime hydrochloride, etamsylate and metoclopramide hydrochloride using 1, 10 phenanthroline-Fe??(Ⅲ) reagent. Scientia pharmaceutica, 2004, 72(1):73-87.
[4] Shenoy K R P. Spectrometric determination of etamsylate in pharmaceutical dosage forms. The Eastern Pharmacist, 2000, 43(2): 135-138.
[5] 混旭，杨维平，章竹君．气动毛细管微滴进样-化学发光法测定酚磺乙胺．高等学校化学学报，2004，25(2)：264-266．
[6] Zhouping Wang, Zhujun Zhang, Zhifeng Fu, Wanfen Luo, Xiao Zhang. Flow-injection chemiluminescence determination of aminomethylbenzoic acid and aminophylline based on N-bromosuccinimide-luminol reaction. Talanta, 2004, 62 (4) 611-617.
[7] 张启龙，蓝静．HPLC法测定酚磺乙胺注射液的含量．山东医药工业，2002，21(2)：16-17．
[8] 汪振辉，张岱，张岩，周漱萍．聚对氨基吡啶化学修饰电极上酚磺乙胺的电化学行为及其溶出伏安法测定．分析化学，2001，29(1)：83-86．
[9] 倪永年．化学计量学在分析化学中的应用[M]．北京：科学出版社，2004：134．[1] 赵芳，吴远远，耿征，王红轩．流动注射化学发光法测定异烟肼．分析化学，2004，32(5)：927-929．
[2] 吕家根，章竹君，罗利荣，田穗康，侯涛．在线自发电源激发的流动注射电致化学发光测定异烟肼．化学学报，2002，61(6)：950-953．
[3] 金鸣，黄河，陈新山．反相高效液相色谱法测定血浆及尿液中的异烟肼．色谱，2002，20(5)：442-445．
[4] 杨维平，张琰图，章竹君．高效液相色谱．化学发光法研究异烟肼和利福平．化学学报，2003，61(2)：303-306．
[5] Jhy-Wen Wu, Hsin-Hui Shih, Shau-Chun Wang, Tung-Hu Tsai. Determination and pharmacokinetic profile of pyrazinamide in rat blood, brain and bile using microdialysis coupled with high-performance liquid chromatography and verfied by tandem mass spectrometry. Analytica Chimica Acta, 2004, 522(2): 231-239.
[6] Aida Mehmedagic, Philippe Verite, Sabine Menager, Christine Tharasse, Christiane Chabenat, Dominique Andre, Olivier Lafont. Determination of pyrazinamide and its main metabolites in rat urine by high-performance liquid chromatographvy. Journal ofChromatoeraphy B. 1997. 695(2): 365-372.
[7] 张维平，杨光，郎惠云．流动注射梯度稀释-原子吸收光谱法间接测定异烟肼．分析实验室，2003，22(6)：26-29．
[8] M.A. Alonso Lormillo, O. Dominguez Renedo, M. J. Amos Martinez. Resolution of ternary mixtures of rifampicin, isoniazid and pyrazinamide by differential pulse polarography and partial least squares method. Analytica Chimica Acta, 2001,449(1-2): 167-177.
[9] 罗立强，汪振辉，周漱萍．阴极溶出伏安法测定异烟肼的研究．分析实验室，1998，17(1)：9-12．
[10] 倪永年．化学计量学在分析化学中的应用[M]．北京：科学出版社，2004：134．