基于UPLC指纹图谱结合化学模式识别的芪参益气滴丸质量控制研究
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摘要
目的采用超高效液相色谱法建立芪参益气滴丸的指纹图谱,并结合化学模式识别技术对其进行系统、全面和科学的质量评价。方法采用Waters超高效液相色谱仪,ACQUITY UPLC?HSS T3色谱柱,以乙腈-0.1%甲酸水为流动相进行梯度洗脱,检测波长为256nm,建立10批次芪参益气滴丸的指纹图谱。通过相似度分析并结合聚类分析(cluster analysis,CA)、主成分分析(principal component analysis,PCA)及正交偏最小二乘法-判别分析(orthogonal partial least squares discriminantanalysis,OPLS-DA)模式识别技术对芪参益气滴丸的总体质量进行分析评价。结果建立的指纹图谱共标定53个共有峰,经对照品进行化学指认并鉴定了其中的14个色谱峰。10批供试品的相似度均>0.94,表明该药物总体质量较为稳定;但通过CA及PCA均发现不同批次药物质量之间仍然存在有微小差异,且主要分为2大类,最后进一步采用OPLS-DA筛选出了导致批次药物质量差异的3个共有峰。结论本研究建立的分析方法科学、准确、可靠且简便易行,指纹图谱结合化学模式识别技术可更加系统、全面地评价芪参益气滴丸的药物质量,同时为今后中药及其制剂更进一步的质量控制研究奠定了坚实的理论基础。
OBJECTIVE To establish the UPLC fingerprint of Qishen Yiqi Dripping pills and conduct a systemic,comprehensive quality evaluation of the drug using a chemical pattern recognition method. METHODS Ultra-high performance liquid chromatography instrument and ACQUITY UPLC? HSS T3 chromatographic column was employed, the separation was performed with the mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution, and the detection wavelength was set at 256 nm to establish the UPLC fingerprint of Qishen Yiqi Dripping pills. Then, the further quality assessment of the drug was carried out by similarity evaluation, cluster analysis(CA), principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). RESULTS Fifty-three peaks were recognised as common peaks in the fingerprint, 14 peaks were identified using standard references. The similarity value of the drugs were all >0.94,indicating a relatively stable quality of the quality. Little difference was then discovered between the batches of the drug by CA and PCA. Finally, 3 peaks were recognised as the quality makers using a OPLS-DA method. CONCLUSION The analysis method established in this study is scientific, accurate, reliable and simple; the drug quality of Qishen Yiqi Dripping pills can be evaluated systematically and comprehensively using a fingerprint combined with chemical pattern recognition technique; what's more, it will also lay a solid theoretical basis for the further quality control of traditional Chinese medicine and its preparations at the same time.
OBJECTIVE To establish the UPLC fingerprint of Qishen Yiqi Dripping pills and conduct a systemic,comprehensive quality evaluation of the drug using a chemical pattern recognition method. METHODS Ultra-high performance liquid chromatography instrument and ACQUITY UPLC? HSS T3 chromatographic column was employed, the separation was performed with the mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution, and the detection wavelength was set at 256 nm to establish the UPLC fingerprint of Qishen Yiqi Dripping pills. Then, the further quality assessment of the drug was carried out by similarity evaluation, cluster analysis(CA), principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). RESULTS Fifty-three peaks were recognised as common peaks in the fingerprint, 14 peaks were identified using standard references. The similarity value of the drugs were all >0.94,indicating a relatively stable quality of the quality. Little difference was then discovered between the batches of the drug by CA and PCA. Finally, 3 peaks were recognised as the quality makers using a OPLS-DA method. CONCLUSION The analysis method established in this study is scientific, accurate, reliable and simple; the drug quality of Qishen Yiqi Dripping pills can be evaluated systematically and comprehensively using a fingerprint combined with chemical pattern recognition technique; what's more, it will also lay a solid theoretical basis for the further quality control of traditional Chinese medicine and its preparations at the same time.
引文
[1]ZHOU L,JIANG X F,SUN Z,et al.Simultaneous determination of eleven constituents in Qishen Yiqi Dropping pills by UPLC-MS/MS combined with pattern recognition[J].Chin Tradit Pat Med(中成药),2017,39(10):2064-2068.
[2]WEI C C,ZHU M D,DU W X,et al.Clinical application of Qishen Yiqi Diwan[J].West J Tradit Chin Med(西部中医药),2011,24(10):102-106.
[3]PENG J J,LI X W,LI D X,et al.Quality identification of Qishen Yiqi Dropping pills by double wavelength ultra performance liquid chromatography fingerprints[J].Cent South Pharm(中南药学),2016,14(11):1188-1193.
[4]LI M,LI R M,ZHANG Y Q,et al.GC fingerprint of volatile components in Qishen Yiqi Dropping pills[J].Chin Tradit Herb Drugs(中草药),2016,47(10):1702-1708.
[5]WANG J,WEI N,ZHAO H Z,et al.Comparison of HPLCand UPLC determination of five active components of Radix et Rhizoma Salviae Miltiorrhizae in Qishenyiqi Dropping pills[J].Chin J Pharm Anal(药物分析杂志),2011,31(9):1678-1682.
[6]FU J Z,SONG S Y,JIANG M,et al.Simultaneous determination of the contents of astragaloside IV,danshensu,protocatechualdehyde,ginsenosides Rg1 and Rb1 in Qishenyiqi Dropping pills by LC-MS[J].Chin Pharm J(中国药学杂志),2012,47(1):61-64.
[7]ZHANG Y P,QIAN X,ZHANG L,et al.Simultaneous determination of five active components in Hechan Tablet by UPLC-MS/MS[J].Pharm Today(今日药学),2017,27(8):521-524.
[8]SUN Z,ZHOU L,ZUO L H,et al.Digital fingerprint of Xuebijing injections by UPLC and content determination of four phenolic acids[J].Chin J Hosp Pharm(中国医院药学杂志),2017,37(11):1060-1064.
[9]YAO L W,LIU Y,ZHENG X W,et al.Application of the fingerprint and characteristic fingerprint technology in traditional Chinese medicinal materials and Chinese patent medicine[J].Chin J New Drugs(中国新药杂志),2018,27(8):934-939.
[10]DENG W,WANG H L,PENG L H,et al.Study on HPLCfingerprint chromatogram of ultrafine granular powder of Epimedii Folium[J].Pharm Today(今日药学),2016,26(5):300-303.
[11]ZHOU L,JIANG X F,ZUO L H,et al.Quantitative and quality evaluation research of multiple principal active components in Guanxin Danshen capsules by MS-principal component analysis[J].Chin J Pharm Anal(药物分析杂志),2017,37(10):1824-1831.
[12]DAI Y,YE Y Q,FENG W B,et al.Application of pattern recognition in quality control of the traditional Chinese medicine[J].J Yunnan Nat Univ(Nat Sci Ed)(云南民族大学学报:自然科学版),2007(4):334-337.
[13]WU Y.Research and application of pattern recognition method for holographic fingerprint of traditional Chinese medicine in quality control of traditional Chinese medicine[D].Wuhan:Central South University for Nationalities(中南民族大学),2013.
[2]WEI C C,ZHU M D,DU W X,et al.Clinical application of Qishen Yiqi Diwan[J].West J Tradit Chin Med(西部中医药),2011,24(10):102-106.
[3]PENG J J,LI X W,LI D X,et al.Quality identification of Qishen Yiqi Dropping pills by double wavelength ultra performance liquid chromatography fingerprints[J].Cent South Pharm(中南药学),2016,14(11):1188-1193.
[4]LI M,LI R M,ZHANG Y Q,et al.GC fingerprint of volatile components in Qishen Yiqi Dropping pills[J].Chin Tradit Herb Drugs(中草药),2016,47(10):1702-1708.
[5]WANG J,WEI N,ZHAO H Z,et al.Comparison of HPLCand UPLC determination of five active components of Radix et Rhizoma Salviae Miltiorrhizae in Qishenyiqi Dropping pills[J].Chin J Pharm Anal(药物分析杂志),2011,31(9):1678-1682.
[6]FU J Z,SONG S Y,JIANG M,et al.Simultaneous determination of the contents of astragaloside IV,danshensu,protocatechualdehyde,ginsenosides Rg1 and Rb1 in Qishenyiqi Dropping pills by LC-MS[J].Chin Pharm J(中国药学杂志),2012,47(1):61-64.
[7]ZHANG Y P,QIAN X,ZHANG L,et al.Simultaneous determination of five active components in Hechan Tablet by UPLC-MS/MS[J].Pharm Today(今日药学),2017,27(8):521-524.
[8]SUN Z,ZHOU L,ZUO L H,et al.Digital fingerprint of Xuebijing injections by UPLC and content determination of four phenolic acids[J].Chin J Hosp Pharm(中国医院药学杂志),2017,37(11):1060-1064.
[9]YAO L W,LIU Y,ZHENG X W,et al.Application of the fingerprint and characteristic fingerprint technology in traditional Chinese medicinal materials and Chinese patent medicine[J].Chin J New Drugs(中国新药杂志),2018,27(8):934-939.
[10]DENG W,WANG H L,PENG L H,et al.Study on HPLCfingerprint chromatogram of ultrafine granular powder of Epimedii Folium[J].Pharm Today(今日药学),2016,26(5):300-303.
[11]ZHOU L,JIANG X F,ZUO L H,et al.Quantitative and quality evaluation research of multiple principal active components in Guanxin Danshen capsules by MS-principal component analysis[J].Chin J Pharm Anal(药物分析杂志),2017,37(10):1824-1831.
[12]DAI Y,YE Y Q,FENG W B,et al.Application of pattern recognition in quality control of the traditional Chinese medicine[J].J Yunnan Nat Univ(Nat Sci Ed)(云南民族大学学报:自然科学版),2007(4):334-337.
[13]WU Y.Research and application of pattern recognition method for holographic fingerprint of traditional Chinese medicine in quality control of traditional Chinese medicine[D].Wuhan:Central South University for Nationalities(中南民族大学),2013.