基于国家药品抽检的宁心宝胶囊质量评价与研究  

Quality Evaluation and Research on Ningxinbao Capsules Based on National Drug Sampling

作　　者：张琳琳 周建良 张文婷 唐登峰 郑成 马临科 马双成[3] ZHANG Lin-lin;ZHOU Jian-liang;ZHANG Wen-ting;TANG Deng-feng;ZHENG Cheng;MA Lin-ke;MA Shuang-cheng(Zhejiang Institute for Food and Drug Control,NMPA Key Laboratory of Quality Evaluation of Traditional Chinese Patent Medicine,Hangzhou310052,China;College of Pharmacy,Hangzhou Normal University,Hangzhou311121,China;National Institutes for Food and Drug Control,Beijing100050,China)

机构地区：[1]浙江省食品药品检验研究院,国家药品监督管理局中成药质量评价重点实验室,杭州310052 [2]杭州师范大学药学院,杭州311121 [3]中国食品药品检定研究院,北京100050

出　　处：《中国药学杂志》2023年第9期831-837,共7页Chinese Pharmaceutical Journal

基　　金：浙江省药品监督管理局科技计划项目资助(2023007);浙江省中医药科技计划项目资助(2023ZF130);浙江省中医药科技计划项目资助(2021ZB178)。

摘　　要：目的 基于国家药品抽检工作,系统性评价宁心宝胶囊的质量以及分析存在的问题,为该品种的质量控制提供参考和建议。方法 对抽样的308批次样品进行标准检验,探索性研究基于核糖体DNA第二内转录间隔区(internal transcribed spacer 2,ITS2)基因测序对宁心宝胶囊样品虫草头孢菌进行菌种鉴定;采用HPLC建立宁心宝胶囊指纹图谱以及同时测定尿嘧啶、次黄嘌呤、尿苷、腺嘌呤、鸟苷和腺苷6个成分含量;采用UPLC测定麦角甾醇含量;采用LC/MS/MS对8种真菌毒素(黄曲霉毒素B1、B2、G1、G2、赭曲霉毒素A、呕吐毒素、玉米赤霉烯酮、T-2毒素)进行筛查。结果 308批次样品依标检验合格率为100%。探索性研究表明,27家企业的48批次样品均能鉴定到目标菌种,但目标菌种的丰度差异较大,范围为0.15%~99.85%。经企业调研发现,目标菌种丰度与原料药来源相关。对308批次样品的HPLC指纹图谱、核苷类成分多指标含量以及麦角甾醇含量测定结果进行综合分析,结果显示所有样品主要分成两类,原料来源于原研企业优于仿制企业。各项目相关性分析表明菌种纯度与指纹图谱相似度、核苷类成分含量和麦角甾醇含量之间呈正相关。真菌毒素污染风险较低。结论 建议质量标准中增加指纹图谱整体控制和核苷类多指标含量和麦角甾醇含量测定项;菌种纯度是影响宁心宝胶囊质量的关键因素,监管部门和原料药生产企业应重点关注菌种传代以及发酵过程中的菌种纯度。OBJECTIVE To systematically evaluate the quality of Ningxinbao capsules,analyze the existing problems,and pro⁃vide some suggestions for the quality control.METHODS A total of 308 batches of samples were tested according to the statutory standard,and the strain identification ofCephalosporium sinensisChen.sp.nov.in Ningxinbao capsules was carried out based on inter⁃nal transcribed spacer 2(ITS2)gene sequencing.HPLC method was used to establish the fingerprint of Ningxinbao capsules and deter⁃mine the contents of six components,namely,uracil,hypoxanthine,uridine,adenine,guanosine,and adenosine.The content of er⁃gosterol was determined by UPLC method.Eight fungal toxins(aflatoxin B1,B2,G1,G2,ochratoxin A,vomitoxin,zearalenone,T⁃2 toxin)were screened by LC/MS/MS method.RESULTS The qualified rate for 308 batches of samples was 100%according to the statu⁃tory standard.The target strains were all detected in 48 batches of samples from 27 enterprises,but the abundance of the target strains var⁃ied widely,ranging from 0.15%to 99.85%.It was found that the abundance of the target strains was related to the source of the API.A total of 308 batches of samples were comprehensively evaluated based on HPLC fingerprinting,contents of nucleoside components and ergosterol,and the results showed that all samples were mainly divided into two categories,and the raw materials from the original enter⁃prises were better than generic companies.The correlation analysis of all items showed a positive correlation between strain purity and fin⁃gerprint similarity,the contents of nucleosides and ergosterol.Ningxinbao capsules showed a low risk of mycotoxin contamina⁃tion.CONCLUSION It is suggested that the statutory standard be improved by adding overall control of fingerprinting and determination of the contents of nucleosides and ergosterol.Due to the purity of the strain is the key factor affecting the quality of Ningxinbao capsules,the regulatory authorities and the related API manufacturers should focus on the purity o

关 键 词：宁心宝胶囊 核糖体DNA第二内转录间隔区 指纹图谱 核苷类成分 麦角甾醇 含量测定 质量评价 

分 类 号：R917[医药卫生—药物分析学] R284[医药卫生—药学]