基于化学计量学、灰色关联度、一测多评多组分定量分析的童康片质量控制研究

目的 建立童康片中13个成分含量测定方法，结合化学计量学及灰色关联度分析（GRA）对其质量进行综合评价。方法 采用高效液相色谱-一测多评法（HPLC-QAMS），以乙腈-甲醇（9∶1）-0.5%磷酸水溶液为流动相梯度洗脱；检测波长分别为300 nm（检测柚皮芸香苷、橙皮苷）、254 nm（检测升麻素苷、升麻素、亥茅酚苷、毛蕊异黄酮葡萄糖苷、芒柄花苷、9,10-二甲氧基紫檀烷-3-O-β-D-葡萄糖苷）、203 nm（检测黄芪甲苷、薯蓣皂苷元）和220 nm（检测尿囊素、白术内酯Ⅲ、白术内酯Ⅰ）；结合化学计量学和GRA对多指标成分含量进行差异性分析。结果 方法学验证结果均符合《中华人民共和国药典》2020年版要求。化学计量学分析显示，橙皮苷、9,10-二甲氧基紫檀烷-3-O-β-D-葡萄糖苷、升麻素苷、白术内酯Ⅲ和尿囊素是影响童康片质量的主要潜在标志物。GRA相对关联度为0.297 6~0.667 8，同一时期生产的童康片质量差异小。结论 HPLC-QAMS同时测定童康片中13个成分含量，简便实用，化学计量学和GRA可用于评价童康片的整体质量。

Study on Quality Control of Tongkang Tablets Based on Chemometrics, GRA and QAMS Multicomponent Quantitative Analysis

Objective To establish a method for the content determination of 13 components in Tongkang Tablets, and comprehensively evaluate the quality of Tongkang Tablets by chemometrics and grey relational analysis (GRA).Method HPLC-quantitative analysis of multi-components by single marker (QAMS) method was used, with acetonitrile-methanol (9:1) -0.5% phosphoric acid aqueous solution as mobile phase for gradient elution; the detection wavelengths were 300 nm (for narirutin and hesperidin), 254 nm (for prim-O-glucosylcimifugin, cimifugin, sec-O-glucosylhamaudol, calycosin 7-O-β-D-glucopyranoside, ononin and 9,10-dimethoxy-pterocarpane-3-O-β-D-glucoside), 203 nm (for astragaloside Ⅳ and diosgenin), and 220 nm (for allantoin, atractylenolide Ⅲ and atracylenolide Ⅰ), respectively. Chemometrics and GRA were used for differential analysis of the results of multi-index component content.Results The results of methodological validation all met the requirements in the Chinese Pharmacopoeia (2020 edition). Chemometric analysis showed that hesperidin, 9,10-dimethoxy-pterocarpane-3-O-β-D-glucoside, prim-O-glucosylcimifugin, atractylenolide Ⅲ and allantoin were the main potential markers affecting the quality of Tongkang Tablets. The relative correlation degree of GRA was 0.297 6-0.667 8, and the quality difference of Tongkang Tablets produced in the same period was small.Conclusion The HPLC-QAMS method can simultaneously determine the contents of 13 components in Tongkang Tablets, which is simple and practical. Chemometrics and GRA can be used to evaluate the overall quality of Tongkang Tablets.