总有机碳法检测丹参多酚酸生产设备的清洗残留  

Determination of production equipment cleaning residue in Salvianolic Acids for Injection by total organic carbon analysis method

作　　者：陈雪艳 胡红艳 曹宁 高倩 胡靖[1,2] 鞠爱春 CHEN Xueyan;HU Hongyan;CAO Ning;GAO Qian;HU Jing;JU Aichun(Tianjin Tasly Pride Pharmaceutical Co.,Ltd.,Tianjin 300410,China;Tianjin Key Laboratory of Safety Evaluation Enterprise of Traditional Chinese Medicine Injections,Tianjin 300410,China)

机构地区：[1]天津天士力之骄药业有限公司,天津300410 [2]天津市中药注射剂新技术企业重点实验室,天津300410

出　　处：《药物评价研究》2021年第4期756-761,共6页Drug Evaluation Research

基　　金：天津市科技重大专项与工程(18ZXXYSY00120)。

摘　　要：目的建立总有机碳(TOC)分析技术实现快速分析注射用丹参多酚酸主要原料丹参多酚酸的生产设备清洗残留。方法对TOC法的专属性、准确度、精密度(重复性与中间精密度)、线性、检测限、定量限与耐用性进行验证。将不同含碳浓度的丹参多酚酸样品溶液滴于不锈钢板上,擦拭取样,计算取样回收率。结合方法学研究数据评价TOC法用于丹参多酚酸生产设备清洗残留检测的效果。结果空白溶剂与空白棉签对测定丹参多酚酸生产设备清洗残留的干扰较小;准确度的平均回收率为103%,重复性与中间紧密度的RSD值均小于3%;丹参多酚酸理论含碳质量浓度在0~30μg/mL线性关系良好(r=0.9999),定量限为55 ng/mL,检测限为18 ng/mL。供试品溶液在冰箱2~10℃中储存的有效期为48 h,酸碱耐用性范围为5~9;平均取样回收率为100%。设备改造的清洁验证实验中,丹参多酚酸生产设备清洗残留的检测结果最大值为2.22μg/mL,均低于验证标准。结论TOC分析方法快速、准确、简便,可用于丹参多酚酸生产设备的残留检测,为设备清洗洁净程度的判断提供有力依据。Objective To establish total organic carbon(TOC)analysis technology to realize rapid analysis of production equipment cleaning residue for salvianolic acids,the main raw material of Salvianolic Acids for Injection.Methods TOC method was verified for specificity,accuracy,precision,linearity,limit of detection,limit of quantitation and robustness.Drop the salvianolic acids sample solutions with different carbon concentrations on the stainless steel plate,wipe the samples,and calculate the sampling recovery rate.Combining methodological research data to evaluate the effect of TOC method in the detection of production equipment cleaning residue for salvianolic acids.Results Blank solvent and blank cotton swabs had little interference in the determination of salvianolic acids production equipment cleaning residue.The mean recovery in accuracy test was 103%.Both the RSDs in reproducibility and intermediate precision tests were less than 3%.Good linearity(r=0.9999)was observed in the standard curves of theoretical carbon content in the range of 0-30μg/mL.LOD was 18 ng/mL and LOQ was 55 ng/mL.The validity period of the test solution stored in the refrigerator(2-10℃)was 48 h,and the acid-base durability range was 5—9.The average sampling recovery rate was 100%.In the cleaning verification experiment of equipment modification,the maximum detection result of the production equipment cleaning residue for Salvianolic Acids was 2.22μg/mL,which are all lower than the verification standard.Conclusion Total organic carbon(TOC)analysis method is rapid,accurate and simple.It can be used for residue detection of salvianolic acids production equipment,which provides a strong basis for the determination of the cleanliness of equipment cleaning.

关 键 词：总有机碳(TOC) 注射用丹参多酚酸 生产设备 清洗残留 丹参多酚酸 

分 类 号：R927.2[医药卫生—药学]