牛黄清胃丸对照制剂的建立

目的：建立牛黄清胃丸对照制剂，并对其进行标定。方法：优选道地优质原料制备对照制剂。采用显微和薄层色谱法进行全处方鉴别。分别采用薄层色谱、气相色谱-串联质谱、高效液相色谱法检查土大黄苷、留兰香和非法染色。分别采用电感耦合等离子体质谱、气质联用、免疫亲和柱-高效液相色谱-柱后光化学衍生、离子色谱法测定重金属及有害元素、农药、黄曲霉毒素、二氧化硫等有害残留。采用超高效液相色谱法测定黄柏、栀子、连翘、菊花、枳实、黄芩、甘草、大黄含量，并建立指纹图谱。最后对对照制剂的均匀性和稳定性加以评估。结果：经全处方鉴别，可检出所有17个药味；真实性和安全性检查结果显示，无化工染料染色或混伪品掺伪，有害残留低。建立的指纹图谱含43个特征峰。盐酸小檗碱、栀子苷、连翘酯苷A、3，5-O-二咖啡酰奎宁酸、橙皮苷、黄芩苷、甘草酸、大黄酚含量分别为1.91、1.65、2.17、0.67、1.20、3.62、0.83、0.16 mg·g^-1。均匀性和稳定性符合规定。结论：牛黄清胃丸对照制剂的建立，为制剂的质量评价和控制提供了实物对照，并为中药对照制剂的研制和应用提供了示范和参考。

Objective: To establish and certificate Niuhuang Qingwei pills reference drug. Methods: Geoherbs with high quality were selected to prepare the reference drug. Microscopic and thin layer chromatography (TLC) methods were used to identify the whole ingredients. Rhaponticin,Menthae Spicatae Herba and illegal dyes were tested by TLC,gas chromatography-tandem mass spectrometry (GC-MS/MS) and high performance liquid chromatography (HPLC) methods,respectively. Harmful residues including heavy metals and harmful elements,pesticides,aflatoxins and sulfur dioxide were determined by inductively coupled plasma mass spectrometry (ICP-MS),gas chromatography-mass spectrometry (GC-MS),high performance liquid chromatography with fluorescence detection after immunoaffinity column clean-up (IC-HPLC-FD) and ion-chromatography (IC) methods,respectively. Ultra performance liquid chromatography (UPLC) method was applied in assay of Phellodendrl Chinensis Cortex,Gardeniae Fructus,Forsythiae Fructus,Chrysanthemi Flos,Aurantii Immaturus Fructus,Scutellariae Radix,Glycyrrhizae Radix et Rhizoma and Rhei Radix et Rhizoma as well as establishment of the fingerprint. Finally,homogeneity and stability evaluations were conducted to the reference drug. Results: All 17 ingredients were found by whole-ingredient identification. Authentic and safety tests showed no chemical dye nor adulterant and low level of harmful residues. 43 peaks were characterized in the fingerprint. Contents of berberine hydrochloride,geniposide,forsythiaside A,3,5-dicaffeoyl quinic acid,hesperidin,baicalin,glycyrrhizic acid and chrysophanol were 1.91,1.65,2.17,0.67,1.20,3.62,0.83 and 0.16 mg·g^-1,respectively. Homogeneity and stability met the requirements. Conclusion: Establishment of Niuhuang Qingwei pills reference drug offers physical reference substance for quality evaluation and control of the corresponding Chinese patent medicine,and provides model and reference for development and application of traditional Chinese medicine (TCM) reference drug.

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