双黄连口服液质量一致性评价研究

Quality Consistency Evaluation of Shuanghuanglian Oral Liquid

目的:探索建立双黄连口服液(SHLO)质量一致性评价方法,并对常见市售8个厂家的产品进行质量分级。方法:建立SHLO中6个指标成分的高效液相色谱含量测定方法,从同厂家不同批次、不同厂家角度分析样品含量均一性;用3个质量一致性参数[批内一致性差异(PA)、批间一致性差异(PB)、指纹图谱相似率(PC)]表征不同厂家产品质量一致性水平;运用主成分分析(PCA)模型提取一致性区分因子(P),实现对8个厂家样品质量一致性分级。结果:建立的高效液相色谱含量测定方法简便且方法学验证合格;40批样品中绿原酸、黄芩苷、连翘苷的质量浓度分别为0.66~1.25、12.71~21.89、0.39~0.66 mg·mL^(–1),均符合《中华人民共和国药典》(以下简称《中国药典》)2020年版对该制剂的限度要求,非《中国药典》2020年版指标成分新绿原酸、连翘酯苷A、汉黄芩苷的质量浓度分别为0.75~1.44、0.07~0.94、0.001 3~1.930 0 mg·mL^(–1),且同厂家样品均一性较好、不同厂家样品存在一定差异;8个厂家样品PA为1.2%~7.7%、PB为16.6%~39.1%、PC为99.3%~99.9%,依据P可将8个生产厂家样品分为3类,其中厂家F、R产品的一致性较好。结论:建立了简便的SHLO多成分定量方法,结合3个一致性评价参数和PCA模型可对不同生产厂家样品质量进行区分,数据结果可为各生产厂家质量标准提升提供参考。

Objective:To establish a method for evaluating the quality consistency of Shuanghuanglian Oral Liquid(SHLO),and to grade the quality of eight commonly products.Methods:A HPLC method was established to determine six index components in SHLO,and the uniformity of samples from different batches of the same manufacturer and different manufactures was analyzed.Three evaluation parameters for quality consistency(in-batch content consistency difference PA,inter-batch content consistency difference PB,and fingerprint similarity PC)were used to characterize the quality consistency of the products from different manufactures.Principal component analysis(PCA)model was employed to extract consistency factor(P),and the quality consistency of the samples from eight manufacturers was graded.Results:The established HPLC method was simple and qualified.The mass concentrations of chlorogenic acid,baicalin,and phillyrin in forty batches of samples were 0.66-1.25,12.71-21.89,0.39-0.66 mg∙mL^(-1),respectively,which all met the requirements in Chinese Pharmacopoeia(2020 edition).As for non-pharmacopoeia indexes(neochlorogenic acid,forsythoside A,and wogonoside),their mass concentrations were 0.75-1.44,0.07-0.94,0.0013-1.9300 mg∙mL^(-1),respectively.Samples of the same manufacturer had good uniformity,while those from different manufacturers presented certain differences.For the samples from eight manufacturers,PAwas between 1.2%and 7.7%,PB between 16.6% and 39.1%,and PC between 99.3% and 99.9%,and they were divided into three categories according to P.Among them,samples from manufactures F and R had desirable consistency.Conclusion:A simple multi-component quantitative method for SHLO was constructed.The three consistency evaluation parameters combined with PCA model distinguished the quality of samples from different manufacturers.The data provided references for manufacturers to improve quality standards.