计算滴定法测定药物含量
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摘要
药物的安全为世人所关注,而药品中药物的含量是药物安全的一个重要指标,因此测定药物的含量也就显得非常重要。目前药物含量的测定方法主要有高效液相色谱法、气相色谱法、分光光度法、抗生素微生物检定法、电位滴定法、非水滴定法等等,而以计算滴定法尤其以恒电位滴定法对药物含量进行测定的研究尚不多见。本文用计算滴定法的两点滴定法和恒电位滴定法对药物含量进行了测定,主要做了以下工作:(1)以银-氯化银电极为指示电极,以硝酸银为滴定剂,采用两点滴定法测定盐酸左旋咪唑片、盐酸奈福泮片、盐酸美西律片、盐酸地芬尼多片四种药物的含量。(2)以氢离子选择性电极为指示电极,用恒电位滴定法测定酒石酸美托洛尔片、西米替丁片、硫酸沙丁胺醇片、尼可刹米注射液的含量。(3)将上述两种方法测定的结果与《中华人民共和国药典》标准方法(非水滴定法、紫外分光光度法)测定的结果进行了对比,实验结果良好,对照误差基本控制在3%以内。(4)对非水滴定中出现的问题、药物辅料是否影响实验结果、实验误差及造成实验误差的各种因素进行了分析和讨论。
The pharmic safety attracts the attention of the world people.The pharmic content is one of the most important safety factors.So determination of pharmic content is very important and necessary.At pesent,there are many methods used to determine pharmic content,e.g.High Performance Liquid Chromatography(HPLC), Gas Chromatography(GC), Ultraviolet(UV), Non-aqueous Titration and so on .But it is not easy to find reports about determination of pharmic content by calculating titration method, especially Multivariate calibration titration.This study used two methods to determine pharmic content. The job includes:(1) Ag-AgCl electrode as the directing electrode, AgNO_3 as the titrant, two-point titration was used to determine the contents of Levamisole Hydrochloride、Difenidol Hydrochloride、Nefopam Hydrochloride and Mexiletinc Hydrochloride.(2)Hydrogen ion selective electrode as the directing electrode, multivariate calibration titration was used to determine the contents of Cimetidine、Metoprolol Tartrate、Salbutaol Sulfate and Nikethamide. (3) The results of two-point titration method and multivariate calibration titration method are compared to the results of standard method in China Pharmacopeia. All results are satisfying. The errors of the determination are all under 3%. (4) The troubles in non-aqueous titration, the affection of pharmceutial necessities, the errors and the factors which may cause errors are analysised and discussed.
The pharmic safety attracts the attention of the world people.The pharmic content is one of the most important safety factors.So determination of pharmic content is very important and necessary.At pesent,there are many methods used to determine pharmic content,e.g.High Performance Liquid Chromatography(HPLC), Gas Chromatography(GC), Ultraviolet(UV), Non-aqueous Titration and so on .But it is not easy to find reports about determination of pharmic content by calculating titration method, especially Multivariate calibration titration.This study used two methods to determine pharmic content. The job includes:(1) Ag-AgCl electrode as the directing electrode, AgNO_3 as the titrant, two-point titration was used to determine the contents of Levamisole Hydrochloride、Difenidol Hydrochloride、Nefopam Hydrochloride and Mexiletinc Hydrochloride.(2)Hydrogen ion selective electrode as the directing electrode, multivariate calibration titration was used to determine the contents of Cimetidine、Metoprolol Tartrate、Salbutaol Sulfate and Nikethamide. (3) The results of two-point titration method and multivariate calibration titration method are compared to the results of standard method in China Pharmacopeia. All results are satisfying. The errors of the determination are all under 3%. (4) The troubles in non-aqueous titration, the affection of pharmceutial necessities, the errors and the factors which may cause errors are analysised and discussed.
引文
[1]马广慈,唐任寰,郑斯成.药物分析方法与应用,北京:科学技术出版社,2000
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[3]倪永年,金玲.计算滴定分析应用及进展.分析化学,1996,24(10):1219-1226
[4]Yongnian Ni.Simultaneous determination of mixtures of acids by potentiometric titration.Anal.Chem.Acta,1998,367:145-152
[5]Yongnian Ni,Aiguo Wu.imultaneous determination of halide and thiocyanate ions by potentiometric precipitation titration and multivariate calibrationAnal.Chem.Acta,1999,390:117-123
[6]Yongnian Ni,Zhaohong Peng.Determination of mixed metal ions by complexometric titration and monlinear partial least squares calibration.Anal.Chem.Acta,1995,304:217-222
[7]Zhu Zhongliang,Li Tonghua,Lu Zhunjun.Simultaneous determination of mixture of very weak acids or bases by two-dimensional pH titration.Gaodeng Xuexi Huaxue Xuebao,1995,16(9):1368-70
[8]张云.计算滴定分析法的分类及其进展.分析科学学报,2006,22(6):715-719
[9]林文如,刘慧明,洪水生.酸碱电位双点滴定法在药物分析中的应用.分析测试学报,1995,14(4):57-61
[10]林文如,张焕新.电位双点滴定法测定巴比妥类药物.分析试验室,1993,12(6):50-52
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[17]郄文娟,冯俊贤,黄鸿雁等.两点电位滴定法测定维生素B6的含量.河北师范大学学报(自然科学版),2001,25(3):368-369
[18]郄文娟,冯俊贤,黄鸿雁等.两点电位滴定法测定盐酸二甲双胍.理化检验-化学册,2002,38(12):632-633
[19]冯俊贤,宋丽英,李素娟等.两点电位滴定法定维生素B1.分析化学,1999,25(4):453-456
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[21]冯俊贤,李素娟,郄文娟等.两点电位滴定法及其应用.分析化学,2002,30(3):337-340
[22]修荣,黄超伦,王伟等.酸碱双点电位法测定盐酸环丙沙星的含量.分析科学学报,2005,21(3):351-352
[23]Van den Berg,C.M.G.and Howard Rogers.Determination of alkalinities of estuarine waters by a two-point potentiometric titration.Marine Chemistry,1987,20(3):219-226
[24]刘辉,修荣.两点电位滴定法测定盐酸雷尼替丁的含量 河北师范大学学报(自然科学版),2002,26(5):498-500
[25]黄曦,庄幼龄.酸碱电位双点滴定法测定萘普生的含量.海峡医药,1995,7(4):26-27
[26]张云,孙健,于雪涛等.非平衡态-恒电位配位滴定法同时测定铁和铝.分析化学,2005,33(12):1764-1766
[27]张云,褚亮亮,许圆等.恒电位氟-铝配位滴定法测定铝的研究.分析试验室,2005,24(3):44-47
[28]张云,李大鹏,杨立等.氟-铝络合滴定计算分析法测定乙醇-水介质中的铝.分析化学,2005,33(7):947-950
[29]《国内外药品标准对比分析手册》编委会,国内外药品标准对比分析手册,北京,化学工业出版社,2003
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[31]张战伟,陈永华,宋传敏.旋光法测定盐酸左旋咪唑及其注射液含量.中国兽药杂志,2006,40(1):26-28
[32]Du Preez J L,Lotter A P.Solid-phase extraction and HPLC determination of levamisole hydrochloride in sheep plasma.The Onderstepoort journal of veterinary research 1996,63,(3):209-211.
[33]J.Martinez Calatayud,Campins Falco.Determination of levamisole hydrochloride with HgI_4~(2-)by a turbidimetfic method and flow-injection analysis.Talanta,1986,33(6):685-687
[34]宋宁宁.电位滴定法测定盐酸左旋咪唑含量.药物分析杂志(增刊),1998:247-248
[35]时玉姣.紫外分光光度法测定盐酸左旋咪唑片含量.桂林医学院学报,1994,2:96-98
[36]郭怀忠,崔秀彦,杨准.盐酸盐酸地芬尼多片含量的HPLC测定.中国医药工业杂志,2000,31(4):166-167
[37]Wen Pan,Yingju Liu,Shouzhuo Yao,etc.Determination of difenidol hydrochloride by capillary electrophoresis with electrochemiluminescence detection.Journal of Chromatography B,2006,831(1-2):17-23
[38]付萍萍,郭怀忠,张瑞华等.一阶导数光谱法测定盐酸盐酸地芬尼多片的含量.中国药品标准,2004,5(2):51-53
[39]付萍萍,郭怀忠,郑清芬.阴离子表面活性剂滴定法测定盐酸盐酸地芬尼多片的含量及含量均匀度.中国药事,2002,16(8):487-488
[40]黄健,温径纬.盐酸盐酸地芬尼多含量测定方法的研究.青海医学院学报,1998,19(4):9-10
[41]冯淑华,张庆伟,庞淑婉.高效液相色谱法测定盐酸奈福泮缓释片的含量.中国现代应 用药学杂志,2006,23(9):904-905
[42]赵晓萌,董淳,徐群英等.高效液相色谱法测定血浆中平痛新的浓度.中国药房,2001,12(6):350-351
[43]陆兵,石庭森.酸性染料法测定盐酸平痛新含量.药学分析杂志,1995,15(1):54-55.
[44]王永飞,李继红.固定pH滴定法测定弱酸性药物盐酸美西律.化学工程,2005,116(5):21-22
[45]许竹梅,赵学燕.高效液相色谱法测定盐酸美西律片的含量.中国药业,2005,14(4):43
[46]刘雪英,张巍巍,苗青.高效液相色谱荧光法测定Beagle犬血浆中酒石酸美托洛尔对映体浓度.中国药房,2006,17(15):1131-1132
[47]K.Veeran Gowda,Uttam Mandal,P.Senthamil Selvan,etc.Liquid chromatography tandem mass spectrometry method for simultaneous determination of metoprolol tartrate and ramipril in human plasma Journal of Chromatography B,2007,858(1-2):13-21
[48]Pal P.N.S,Shenoy K.R.P,Paidey etc.Simultaneous reverse phase liquid chromatographic determination of metoprolol tartrate and hydrochlorthiazide in tablets.Indian Journal of Pharmaceutical Sciences,2005,67(5);608-610
[49]Guzin Alpdo an,Sidika Sungur.AAS and spectrophotometric methods for the determination metoprolol tartrate in tablets Spectrochimica Acta Part A:Molecular and Biomolecular Spectroscopy,1999,55(13):2705-2709
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[52]Tahira Iqbal,Chetan S.Karyekar,Minori Kinjo,etc.Validation of a simplified method for determination of cimetidine in human plasma and urine by liquid chromatography with ultraviolet detection.Journal of Chromatography B,2004,799(2):337-341
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[55]左文坚.HPLC法测定硫酸沙丁胺醇片的含量.中国药学杂志,1996,31(12):754-755
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[57]Lili Chen,Linchuan Liao,Zhong Zuo,etc.Simultaneous determination of nikethamide and lidocaine in human blood and cerebrospinal fluid by high performance liquid chromatography Journal of Pharmaceutical and Biomedical Analysis,2007,43(5):1757-1762
[58]焦更生,曹惠兰.间接原子吸收法测定尼可刹米.分析试验室,2004,23(5):71-73
[2]吴琼诗,李光耀,王玉.非水滴定法测定药物含量的不确定度评定.广东医学院学报,2005,21(2):155-157
[3]倪永年,金玲.计算滴定分析应用及进展.分析化学,1996,24(10):1219-1226
[4]Yongnian Ni.Simultaneous determination of mixtures of acids by potentiometric titration.Anal.Chem.Acta,1998,367:145-152
[5]Yongnian Ni,Aiguo Wu.imultaneous determination of halide and thiocyanate ions by potentiometric precipitation titration and multivariate calibrationAnal.Chem.Acta,1999,390:117-123
[6]Yongnian Ni,Zhaohong Peng.Determination of mixed metal ions by complexometric titration and monlinear partial least squares calibration.Anal.Chem.Acta,1995,304:217-222
[7]Zhu Zhongliang,Li Tonghua,Lu Zhunjun.Simultaneous determination of mixture of very weak acids or bases by two-dimensional pH titration.Gaodeng Xuexi Huaxue Xuebao,1995,16(9):1368-70
[8]张云.计算滴定分析法的分类及其进展.分析科学学报,2006,22(6):715-719
[9]林文如,刘慧明,洪水生.酸碱电位双点滴定法在药物分析中的应用.分析测试学报,1995,14(4):57-61
[10]林文如,张焕新.电位双点滴定法测定巴比妥类药物.分析试验室,1993,12(6):50-52
[12]林文如.电位双点滴定法研究.福州大学学报(自然科学版),1996,24(5):87-90
[13]张云,杨立.单点滴定与双点滴定铈量法测定Fe(Ⅱ).分析试验室,2003,22(4):21-23
[14]张云,谭超.沉淀单点滴定法与双点滴定法研究.分析试验室,2004,23(11):9-12
[15]张云.沉淀双点滴定法.化学世界,1995,1:35-37
[16]张云.单点滴定法和双点滴定法.大学化学,1997,12(1):31-33
[17]郄文娟,冯俊贤,黄鸿雁等.两点电位滴定法测定维生素B6的含量.河北师范大学学报(自然科学版),2001,25(3):368-369
[18]郄文娟,冯俊贤,黄鸿雁等.两点电位滴定法测定盐酸二甲双胍.理化检验-化学册,2002,38(12):632-633
[19]冯俊贤,宋丽英,李素娟等.两点电位滴定法定维生素B1.分析化学,1999,25(4):453-456
[20]冯俊贤,王秀卿,王立平等.两点电位滴定法测定盐酸曲马多含量.分析化学,2001,29(12):1487
[21]冯俊贤,李素娟,郄文娟等.两点电位滴定法及其应用.分析化学,2002,30(3):337-340
[22]修荣,黄超伦,王伟等.酸碱双点电位法测定盐酸环丙沙星的含量.分析科学学报,2005,21(3):351-352
[23]Van den Berg,C.M.G.and Howard Rogers.Determination of alkalinities of estuarine waters by a two-point potentiometric titration.Marine Chemistry,1987,20(3):219-226
[24]刘辉,修荣.两点电位滴定法测定盐酸雷尼替丁的含量 河北师范大学学报(自然科学版),2002,26(5):498-500
[25]黄曦,庄幼龄.酸碱电位双点滴定法测定萘普生的含量.海峡医药,1995,7(4):26-27
[26]张云,孙健,于雪涛等.非平衡态-恒电位配位滴定法同时测定铁和铝.分析化学,2005,33(12):1764-1766
[27]张云,褚亮亮,许圆等.恒电位氟-铝配位滴定法测定铝的研究.分析试验室,2005,24(3):44-47
[28]张云,李大鹏,杨立等.氟-铝络合滴定计算分析法测定乙醇-水介质中的铝.分析化学,2005,33(7):947-950
[29]《国内外药品标准对比分析手册》编委会,国内外药品标准对比分析手册,北京,化学工业出版社,2003
[30]中华人民共和国卫生部药典委员会.中华人民共和国药典.北京,化学工业出版社,1995:Ⅲ,584,604,661,675,776,223,906,190,附录18,附录168
[31]张战伟,陈永华,宋传敏.旋光法测定盐酸左旋咪唑及其注射液含量.中国兽药杂志,2006,40(1):26-28
[32]Du Preez J L,Lotter A P.Solid-phase extraction and HPLC determination of levamisole hydrochloride in sheep plasma.The Onderstepoort journal of veterinary research 1996,63,(3):209-211.
[33]J.Martinez Calatayud,Campins Falco.Determination of levamisole hydrochloride with HgI_4~(2-)by a turbidimetfic method and flow-injection analysis.Talanta,1986,33(6):685-687
[34]宋宁宁.电位滴定法测定盐酸左旋咪唑含量.药物分析杂志(增刊),1998:247-248
[35]时玉姣.紫外分光光度法测定盐酸左旋咪唑片含量.桂林医学院学报,1994,2:96-98
[36]郭怀忠,崔秀彦,杨准.盐酸盐酸地芬尼多片含量的HPLC测定.中国医药工业杂志,2000,31(4):166-167
[37]Wen Pan,Yingju Liu,Shouzhuo Yao,etc.Determination of difenidol hydrochloride by capillary electrophoresis with electrochemiluminescence detection.Journal of Chromatography B,2006,831(1-2):17-23
[38]付萍萍,郭怀忠,张瑞华等.一阶导数光谱法测定盐酸盐酸地芬尼多片的含量.中国药品标准,2004,5(2):51-53
[39]付萍萍,郭怀忠,郑清芬.阴离子表面活性剂滴定法测定盐酸盐酸地芬尼多片的含量及含量均匀度.中国药事,2002,16(8):487-488
[40]黄健,温径纬.盐酸盐酸地芬尼多含量测定方法的研究.青海医学院学报,1998,19(4):9-10
[41]冯淑华,张庆伟,庞淑婉.高效液相色谱法测定盐酸奈福泮缓释片的含量.中国现代应 用药学杂志,2006,23(9):904-905
[42]赵晓萌,董淳,徐群英等.高效液相色谱法测定血浆中平痛新的浓度.中国药房,2001,12(6):350-351
[43]陆兵,石庭森.酸性染料法测定盐酸平痛新含量.药学分析杂志,1995,15(1):54-55.
[44]王永飞,李继红.固定pH滴定法测定弱酸性药物盐酸美西律.化学工程,2005,116(5):21-22
[45]许竹梅,赵学燕.高效液相色谱法测定盐酸美西律片的含量.中国药业,2005,14(4):43
[46]刘雪英,张巍巍,苗青.高效液相色谱荧光法测定Beagle犬血浆中酒石酸美托洛尔对映体浓度.中国药房,2006,17(15):1131-1132
[47]K.Veeran Gowda,Uttam Mandal,P.Senthamil Selvan,etc.Liquid chromatography tandem mass spectrometry method for simultaneous determination of metoprolol tartrate and ramipril in human plasma Journal of Chromatography B,2007,858(1-2):13-21
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