多维高效液相色谱法的建立及其在清开灵质量控制中的应用
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摘要
中药成分繁多、性质复杂,尽管指纹图谱在一定程度上提高了中药及其制剂的质量,但采用单一的分离模式难以解决分离与检测两大问题,造成信息的大量丢失。本课题选择清开灵注射液为分析样品,运用多维高校液相色谱技术对清开灵注射液中进行全面快速分析,涵盖了极性大的氨基酸类、核苷类成分,中等极性的有机酸类、栀子苷、黄芩苷类成分以及极性较小得胆酸类成分。
本实验分三部分:
第一部分多维高效液相色谱法的建立,在多维高效液相色谱的理论指导下,设想了不同的连接模式,并对每种模式进行实践研究,分析了每种模式下可能的影响因素,建立了适合分析清开灵注射液样品分析的色谱连接模式。对色谱分析的色谱柱、流动相、检测条件进行了考察,以清开灵注射液中六类十一种成分为指标(核苷类的腺苷、鸟苷,有机酸类的咖啡酸、绿原酸,氨基酸类的苯丙氨酸、色氨酸,环烯醚萜类的栀子苷、胆酸类的猪去氧胆酸、鹅去氧胆酸、胆酸,以及黄芩苷)建立了清开灵样注射液品的色谱分析方法。
第二部分对多维高效液相色谱法进行了方法学考察,通过系统适应性、精密度、稳定性、线性、检测限、定量限、回收率等实验,证明该模式下所建立的对的清开灵注射液分析方法符合要求,可用于多成分的定量分析。
第三部分应用多维高效液相色谱技术,配合紫外检测器、蒸发光检测器对清开灵注射液的十一种指标性成分进行定量分析,配合质谱检测器、电化学检测器对清开灵注射液进行定性分析,从而提高了该制剂的质量标准。同时对该研究所建立的多维色谱技术进行了理论上的探讨,包括其传递技术、色谱参数的优化,为以后的工作奠定了基础。
总之,本研究建立了适合清开灵注射液分析的多维高效液相色谱技术,并利用该技术提高了清开灵注射液的质量标准,为中药及其复方的全成分、快速分析提供了一种研究思路,其在理论上、实践中的探讨研究为多维高效液相在中药成分分析中的研究奠定了工作基础。
Due to the numerous ingredients and complicated characters of Traditional Chinese Herbs, a large quantity of related information has lost by using a single separation model, since it can hardly solve the separation and detection problems, though fingerprint spectrum has, to a certain degree, elevated the quality of Chinese Herbs and its preparations. Selecting Qingkailing injection as the analyzing sample, our goal is to use multidimensional HPLC to detect and analyze Qingkailing injection fleetly and completely. Analyzing targets cover high polarities, such as, amino acid and nucleotide, middle polarities, such as, organic acid, geniposide, baicalin, low polarities, such as, bile acid.
This experiment contains three parts:
1. The establishment of multidimensional HPLC. Under the guidance of multidimensional HPLC theory, we assumed different linking patterns, put each of them into practice to analyze respective effecting factors, and finally institute a proper linking model for analyzing the sample of Qingkailing injection. Reviewing the column, mobile phase, detecting condition of chromatography, we established the specific chromatography for Qingkailing sample, depending on the components (6 sorts, 11 species) of Qingkailing as index (nucleotide: adenosine, guanosine; organic acid: caffeic acid, chlorogenic acid; amino acid: phenylalanine, tryptophan; secoiridoid compounds: geniposide; bile acid: hydroxycholic acid, chenodeoxycholoc acid, cholic acid; baicalin)
2. Methodology inspection of multidimensional HPLC. Through the experimentation of system adaptability, precision, stability, linearity, detection limit, quantity limit, recovery ratio, we testified that this model can well accord with the request, and can be used in the multi-ingredients quantitative analysis.
3. By using the technique of Multidimensional HPLC, we carried out quantitative analysis on the 11 index components of Qingkailing injection with ultraviolet detector and evaporation light detector while we put up the relevant qualitative analysis with MS detector and electrochemical detector. As a result, the quality standards of this preparation have been elevated. Meanwhile, we carried through academic discussions on the established multidimensional HPLC technique, including the optimization of transfer technique, chromatography parameter, which indicated that a solid foundation for future research work has been settled.
In conclusion, this research has established the multi-dimensional HPLC technique specifically suited to Qingkailing injection. We improved the quality standard of Qingkailing injection by the application of this technique. What's more, it supplied a train of thought to the fleet and complete analysis of Traditional Chinese Herbs and its preparations. The relevant theoretical and practical discussions and researches settled a solid foundation for the research on the multi-dimensional HPLC analysis on the ingredients of Chinese medicine.
本实验分三部分:
第一部分多维高效液相色谱法的建立,在多维高效液相色谱的理论指导下,设想了不同的连接模式,并对每种模式进行实践研究,分析了每种模式下可能的影响因素,建立了适合分析清开灵注射液样品分析的色谱连接模式。对色谱分析的色谱柱、流动相、检测条件进行了考察,以清开灵注射液中六类十一种成分为指标(核苷类的腺苷、鸟苷,有机酸类的咖啡酸、绿原酸,氨基酸类的苯丙氨酸、色氨酸,环烯醚萜类的栀子苷、胆酸类的猪去氧胆酸、鹅去氧胆酸、胆酸,以及黄芩苷)建立了清开灵样注射液品的色谱分析方法。
第二部分对多维高效液相色谱法进行了方法学考察,通过系统适应性、精密度、稳定性、线性、检测限、定量限、回收率等实验,证明该模式下所建立的对的清开灵注射液分析方法符合要求,可用于多成分的定量分析。
第三部分应用多维高效液相色谱技术,配合紫外检测器、蒸发光检测器对清开灵注射液的十一种指标性成分进行定量分析,配合质谱检测器、电化学检测器对清开灵注射液进行定性分析,从而提高了该制剂的质量标准。同时对该研究所建立的多维色谱技术进行了理论上的探讨,包括其传递技术、色谱参数的优化,为以后的工作奠定了基础。
总之,本研究建立了适合清开灵注射液分析的多维高效液相色谱技术,并利用该技术提高了清开灵注射液的质量标准,为中药及其复方的全成分、快速分析提供了一种研究思路,其在理论上、实践中的探讨研究为多维高效液相在中药成分分析中的研究奠定了工作基础。
Due to the numerous ingredients and complicated characters of Traditional Chinese Herbs, a large quantity of related information has lost by using a single separation model, since it can hardly solve the separation and detection problems, though fingerprint spectrum has, to a certain degree, elevated the quality of Chinese Herbs and its preparations. Selecting Qingkailing injection as the analyzing sample, our goal is to use multidimensional HPLC to detect and analyze Qingkailing injection fleetly and completely. Analyzing targets cover high polarities, such as, amino acid and nucleotide, middle polarities, such as, organic acid, geniposide, baicalin, low polarities, such as, bile acid.
This experiment contains three parts:
1. The establishment of multidimensional HPLC. Under the guidance of multidimensional HPLC theory, we assumed different linking patterns, put each of them into practice to analyze respective effecting factors, and finally institute a proper linking model for analyzing the sample of Qingkailing injection. Reviewing the column, mobile phase, detecting condition of chromatography, we established the specific chromatography for Qingkailing sample, depending on the components (6 sorts, 11 species) of Qingkailing as index (nucleotide: adenosine, guanosine; organic acid: caffeic acid, chlorogenic acid; amino acid: phenylalanine, tryptophan; secoiridoid compounds: geniposide; bile acid: hydroxycholic acid, chenodeoxycholoc acid, cholic acid; baicalin)
2. Methodology inspection of multidimensional HPLC. Through the experimentation of system adaptability, precision, stability, linearity, detection limit, quantity limit, recovery ratio, we testified that this model can well accord with the request, and can be used in the multi-ingredients quantitative analysis.
3. By using the technique of Multidimensional HPLC, we carried out quantitative analysis on the 11 index components of Qingkailing injection with ultraviolet detector and evaporation light detector while we put up the relevant qualitative analysis with MS detector and electrochemical detector. As a result, the quality standards of this preparation have been elevated. Meanwhile, we carried through academic discussions on the established multidimensional HPLC technique, including the optimization of transfer technique, chromatography parameter, which indicated that a solid foundation for future research work has been settled.
In conclusion, this research has established the multi-dimensional HPLC technique specifically suited to Qingkailing injection. We improved the quality standard of Qingkailing injection by the application of this technique. What's more, it supplied a train of thought to the fleet and complete analysis of Traditional Chinese Herbs and its preparations. The relevant theoretical and practical discussions and researches settled a solid foundation for the research on the multi-dimensional HPLC analysis on the ingredients of Chinese medicine.
引文
[1] Giddings J C. Sample dimensionality: a predictor of order-disorder in component peak distribution in multi-dimensional separation. J Chromatogr A, 1995; 703:3-15
[2] Giddings J C. Concepts and comparisons in multi-dimensional separation [J]. JHRC&CC, 1987, 10:319.
[3] 王智聪,张庆合,赵中一,张维冰,李彤. 二维液相色谱切换技术及其应用, 分析化学评述与进展.2005,5:722.
[4] Cortes H J, Ed. Multidimensional Chromatography Techniques and Applications, Chapter I, New York: Marcel Dekker, Inc., 1990
[5]王智聪等, 全二维液相色谱的初步构建及其在山羊血清分离中的应用,.分析化学研究报告,2005,4:437~441
[6] Berkowitz S A. J Liq Chromatogr,1987;10:2771
[7]Stroink T, Wiesea G, Lingemanb H, Bult A, Underberg W JM. Analytica Chimica Acta,2001,444:193～203
[8]张洁,张丽华,张维冰,张玉奎现代仪器,2004,(1):
[7] Horvath C, ElRassi Z. Chromatogr Forum,1986;1:49.
[8] Stringham R W, Regnier F E. J Chromatogr,1987;409:305.
[9] Ramsteiner. Systematic approach to column switching .J Chromatogr, 1988, 456:3
[10]张曾子,姚平经,邹汉法,陈小明,倪坚毅. 双柱切换色谱制备系统设计和实现. 分析化学仪器装置与实验技术.2001,29(11):1353~1356
[11] Unger K K, Racaityte K, Wagner K, et al. Is multi-dimensional high pergormance liquid chromatography (HPLC) an alternative in protein analysis to 2D Gelelectrophoresis? J High Resol Chromatogr, 2000; 23:259-265.
[12] Apfel J A, Alfredson T V, Majors R E. J Chromatogr, 1981; 206:43.
[13] Johnson E L, Gloor R, Majors RE. JChromatogr, 1978; 149:571.
[14] Opiteck G J, Lewis K L, Jorgenson J W. Comprehensive on-line LC/LC/MS of proteins. Anal Chem, 1997, 69: 1518~1524.
[15] Wagner K, Racaityte K, Unger K K, et al. Protein mapping by two-dimensional high performance liquid chromatography. Journal of Chromatography A, 2000, 893: 293~305
[16]王智聪, 张庆合, 张维冰, 李 彤, 赵中一. 全二维液相色谱(IEC/RP)的构建与评价. 高等学校化学学报, 2005, 26(3): 426~429
[17] Rilesy C M, Sternson L A, Repta A J. J Chromatogr, 1983; 276:93
[18] Matsuoka K, Taoka M, IsobeTetal. J Chromatogr,1990; 515:313
[19]Mawuenyega K G, Kaji H, Yamauchi Y, et al. Large-scale identi-fication of Caenorhabditis elegans proteins by multidimensional liquid chromatography-tandem mass spectrometry. Journal of Proteome Research, 2003, 2: 23~35
[20]Link A J, Eng J, Schieltz D M, et al. Direct analysis of protein complexes using mass spectrometry. Nature Biotechnology, 1999, 17: 676~682
[21]Washburn M P, Wolters D, Yates J R. Large-scale analysis of the yeast proteome by multidimensional protein identification tech-nology. Nature Biotechnology, 2001, 19: 242~247
[22] 王智聪等,中国科学 B 辑 化学 2006, 36 (1): 64~70
[23] LecallionJB, SouppartC, AbadieF.Chromatographia,1982;16:158
[24] Sonnefeld WJ, Zoller WH, May W Eetal. Anal Chem,1982;54:723
[25] Takeuchi T, Asai M, Haraguchi H, et al. Direct coupling of capillary liquid chromatography with conventional high-performance liquid chromatography. Journal of Chromatography, 1990, 499: 549~556
[26] Dugo P, Favoino O, Luppino R, et al. Comprehensive two-dimen-sional normal-phase (adsorption)-reversed-phase liquid chroma-tography. Anal Chem, 2004, 76: 2525~2530
[27] Opiteck G J, Ramirez S M, Jorgenson J W. Comprehensive two-dimensional high- performance liquid chromatography for the isolation of overexpressed proteins and proteome mapping. Ana-lytical Biochemistry, 1998, 258: 349~361
[28] Opiteck G J, Jorgenson J W. Two-dimensional SEC/RPLC cou-pled to mass spectrometry for the analysis of peptides. Anal Chem, 1997, 69: 2283~2291
[29] Suzuki K T, Sunaga H, Yajima T. J Chromatogr, 1984;303:131
[30] WeidolfL.JChromatogr,1985;343:85
[31] M ellstroem B. J Ch romatogr, 1988; 424: 425
[32]Ch ioch ila T M P, Edlund P O, Henion J D et al. J Ch romatogr, 1989; 488: 389
[33] Billet H, Wolters R, De Galan Letal. JChromatogr,1986;368:351
[34] Edlund P O, Westerdlund D. J Pharm Biomed Anal,1984;2:315
[35]王春祥 刘文英,HPLC 非手性柱手性柱联用技术和直接进样法在体内手性药物分析中的应用, 国外医学药学分册,1997,24(1)
[1] Buerck J, Roth S, Kraemer K, et al. Application of Fiber optic NIR EFA Sensor System for in situ Monitoring of Aromatic Hydrocabonsin Contaminated Groun Water Hazardous Materials, 2001, 83(12): 11-13
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[1] 张玉奎,王杰,张维冰译,实用高效液相色谱法的建立(第二版),2001,华文出版社,151～176
[2] 王智聪,张庆合,赵中一,张维冰,李彤. 二维液相色谱切换技术及其应用, 分析化学评述与进展.2005,5:722.
[2] Giddings J C. Concepts and comparisons in multi-dimensional separation [J]. JHRC&CC, 1987, 10:319.
[3] 王智聪,张庆合,赵中一,张维冰,李彤. 二维液相色谱切换技术及其应用, 分析化学评述与进展.2005,5:722.
[4] Cortes H J, Ed. Multidimensional Chromatography Techniques and Applications, Chapter I, New York: Marcel Dekker, Inc., 1990
[5]王智聪等, 全二维液相色谱的初步构建及其在山羊血清分离中的应用,.分析化学研究报告,2005,4:437~441
[6] Berkowitz S A. J Liq Chromatogr,1987;10:2771
[7]Stroink T, Wiesea G, Lingemanb H, Bult A, Underberg W JM. Analytica Chimica Acta,2001,444:193～203
[8]张洁,张丽华,张维冰,张玉奎现代仪器,2004,(1):
[7] Horvath C, ElRassi Z. Chromatogr Forum,1986;1:49.
[8] Stringham R W, Regnier F E. J Chromatogr,1987;409:305.
[9] Ramsteiner. Systematic approach to column switching .J Chromatogr, 1988, 456:3
[10]张曾子,姚平经,邹汉法,陈小明,倪坚毅. 双柱切换色谱制备系统设计和实现. 分析化学仪器装置与实验技术.2001,29(11):1353~1356
[11] Unger K K, Racaityte K, Wagner K, et al. Is multi-dimensional high pergormance liquid chromatography (HPLC) an alternative in protein analysis to 2D Gelelectrophoresis? J High Resol Chromatogr, 2000; 23:259-265.
[12] Apfel J A, Alfredson T V, Majors R E. J Chromatogr, 1981; 206:43.
[13] Johnson E L, Gloor R, Majors RE. JChromatogr, 1978; 149:571.
[14] Opiteck G J, Lewis K L, Jorgenson J W. Comprehensive on-line LC/LC/MS of proteins. Anal Chem, 1997, 69: 1518~1524.
[15] Wagner K, Racaityte K, Unger K K, et al. Protein mapping by two-dimensional high performance liquid chromatography. Journal of Chromatography A, 2000, 893: 293~305
[16]王智聪, 张庆合, 张维冰, 李 彤, 赵中一. 全二维液相色谱(IEC/RP)的构建与评价. 高等学校化学学报, 2005, 26(3): 426~429
[17] Rilesy C M, Sternson L A, Repta A J. J Chromatogr, 1983; 276:93
[18] Matsuoka K, Taoka M, IsobeTetal. J Chromatogr,1990; 515:313
[19]Mawuenyega K G, Kaji H, Yamauchi Y, et al. Large-scale identi-fication of Caenorhabditis elegans proteins by multidimensional liquid chromatography-tandem mass spectrometry. Journal of Proteome Research, 2003, 2: 23~35
[20]Link A J, Eng J, Schieltz D M, et al. Direct analysis of protein complexes using mass spectrometry. Nature Biotechnology, 1999, 17: 676~682
[21]Washburn M P, Wolters D, Yates J R. Large-scale analysis of the yeast proteome by multidimensional protein identification tech-nology. Nature Biotechnology, 2001, 19: 242~247
[22] 王智聪等,中国科学 B 辑 化学 2006, 36 (1): 64~70
[23] LecallionJB, SouppartC, AbadieF.Chromatographia,1982;16:158
[24] Sonnefeld WJ, Zoller WH, May W Eetal. Anal Chem,1982;54:723
[25] Takeuchi T, Asai M, Haraguchi H, et al. Direct coupling of capillary liquid chromatography with conventional high-performance liquid chromatography. Journal of Chromatography, 1990, 499: 549~556
[26] Dugo P, Favoino O, Luppino R, et al. Comprehensive two-dimen-sional normal-phase (adsorption)-reversed-phase liquid chroma-tography. Anal Chem, 2004, 76: 2525~2530
[27] Opiteck G J, Ramirez S M, Jorgenson J W. Comprehensive two-dimensional high- performance liquid chromatography for the isolation of overexpressed proteins and proteome mapping. Ana-lytical Biochemistry, 1998, 258: 349~361
[28] Opiteck G J, Jorgenson J W. Two-dimensional SEC/RPLC cou-pled to mass spectrometry for the analysis of peptides. Anal Chem, 1997, 69: 2283~2291
[29] Suzuki K T, Sunaga H, Yajima T. J Chromatogr, 1984;303:131
[30] WeidolfL.JChromatogr,1985;343:85
[31] M ellstroem B. J Ch romatogr, 1988; 424: 425
[32]Ch ioch ila T M P, Edlund P O, Henion J D et al. J Ch romatogr, 1989; 488: 389
[33] Billet H, Wolters R, De Galan Letal. JChromatogr,1986;368:351
[34] Edlund P O, Westerdlund D. J Pharm Biomed Anal,1984;2:315
[35]王春祥 刘文英,HPLC 非手性柱手性柱联用技术和直接进样法在体内手性药物分析中的应用, 国外医学药学分册,1997,24(1)
[1] Buerck J, Roth S, Kraemer K, et al. Application of Fiber optic NIR EFA Sensor System for in situ Monitoring of Aromatic Hydrocabonsin Contaminated Groun Water Hazardous Materials, 2001, 83(12): 11-13
[2] 金玉龙,赵志新. 清开灵注射液的临床研究.中医药学报,1995,10(4):54-56
[3] 齐治家,钱家骏,乔亭泽. 清开灵注射液对实验性肝损伤保护作用的生物化学初步研究. 中医杂志,1981,(5):389
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