基于HPLC多组分定量联合化学计量学及灰色关联度分析的癣宁搽剂质量控制研究

Quality Control Study of Xuanning Liniment Based on HPLC Multi-component Quantitative Combined with Chemometrics and Grey Correlation Analysis

目的 采用高效液相色谱(high performance liquid chromatography,HPLC)法同时检测癣宁搽剂中12个成分含量,并联合化学计量学及灰色关联度分析(grey relational analysis,GRA)对癣宁搽剂质量进行综合评价。方法 以Agilent Extend C_(18)为色谱柱,乙腈-0.1%磷酸(含0.02 mol·L^(-1)磷酸氢二钠)为流动相,同时测定癣宁搽剂中盐酸黄柏碱、盐酸药根碱、盐酸巴马汀、盐酸小檗碱、白鲜碱、黄柏酮、梣酮、东莨菪碱、莨菪碱、苦参碱、氧化槐果碱和氧化苦参碱含量。采用化学计量学挖掘影响癣宁搽剂产品质量的差异标志物。基于灰色关联度法分析不同批次癣宁搽剂各指标成分数据,以相对关联度为测度,对癣宁搽剂综合质量进行评价。结果 12个成分在各自范围内线性关系良好(r>0.999 0),平均加样回收率(n=9)在96.81%~100.25%之间(RSD<2.0%)。化学计量学分析显示盐酸小檗碱、氧化苦参碱、黄柏酮、盐酸巴马汀和苦参碱是影响癣宁搽剂产品质量的主要潜在标志物。灰色关联度分析相对关联度在0.313 8~0.620 4之间,癣宁搽剂存在一定批间差异。结论 建立的HPLC多组分定量联合化学计量学及灰色关联度分析方法,操作便捷、结果准确、全面客观,可用于癣宁搽剂质量的综合评价,为该制剂质量控制提供参考。

OBJECTIVE To establish a high performance liquid chromatography(HPLC) method for simultaneous determination of 12 components in Xuanning liniment,and to comprehensively evaluate the quality of Xuanning liniment combined with chemometrics and grey correlation analysis(GRA).METHODS Agilent Extend C_(18) column was used as the chromatographic column,and acetonitrile-0.1% phosphoric acid(containing 0.02 mol·L^(-1) disodium hydrogen phosphate) was as the mobile phase.The contents of phellodendrine hydrochloride,jatrorrhizine hydrochloride,palmatine hydrochloride,berberine hydrochloride,dictamnine,obacunone,fraxinellone,scopolamine,hyoscyamine,matrine,oxysophocarpine and oxymatrine of Xuanning liniment were determined.Chemometrics was used to mine differential markers affecting the productquality of Xuanning liniment.The relative correlation degree was used to analyze the data of each index component of different batches of Xuanning liniment,and the comprehensive quality of Xuanningliniment was evaluated by GRA.RESULTS The 12 components had good linear relationships within their respective ranges(r>0.999 0),and the average recovery rate(n=9) were 96.81%-100.25%(RSD<2.0%).Chemometric analysis showed that berberine hydrochloride,oxymatrine,obacunone,palmatine hydrochloride and matrine were the main potential markers affecting the quality of Xuanning liniment.The relative correlation degree of GRA were 0.313 8-0.620 4,and there was a certain difference between batches of Xuanning liniment.CONCLUSION The established HPLC multi-component quantitative combined chemometrics and GRA method is convenient,accurate,comprehensive and objective.It can be used for the quality comprehensive evaluation and provide reference for the quality control of Xuanning liniment.