双重造影产气剂质量标准的研究与探讨

Research and discussion on the quality standard of aerogenic agent for double contrast radiography

目的:对双重造影产气剂处方工艺及质量标准相关内容进行研究,结合临床使用需求及样品测定结果,确定合理的方法及限度,为双重造影产气剂质量标准的制定提供参考。方法:采用特征化学反应分别鉴别碳酸氢钠、枸橼酸及钠盐;采用二氧化碳气体发生装置测定产气量,根据临床使用需求,结合样品测定结果,确定产气时间和产气量的方法和限度。对比选择更适用的干燥失重测定法并确定合理的限度;分析确定了微生物限度测定法;确定了溶化性、粒度及装量差异等指标的限度;采用高效液相色谱法测定枸橼酸含量,色谱柱为Phenomenex-C18柱(250 mm×4.6 mm,5μm),流动相为甲醇-0.2%磷酸溶液(5∶95),检测波长215 nm,流速0.8 mL·min^(-1),柱温25℃,进样量10μL。结果:鉴别反应专属性强,阴性无干扰;产气量限度为应不少于360 mL,产气时间应在2 min以内;采用常温减压干燥法测定干燥失重,限度为0.2%;确定微生物限度检查方法并完成方法学验证;溶化性、粒度及装量差异检查均符合药典要求;枸橼酸质量浓度在1.6258~3.7936 mg·mL^(-1)范围内与峰面积线性关系良好(r=0.9999),定量限为10.84μg·mL^(-1),精密度、重复性试验的RSD(n=9)均低于1.5%;平均加样回收率为100.2%,RSD为1.8%;3批样品枸橼酸含量测定结果分别为42.7%、42.8%、41.5%。结论:所建立的质量标准项目全面,方法可行,限度合理,可用于双重造影产气剂的质量控制。

Objective:To study the prescription technology and relevant contents of quality standards of aerogenic agent for double contrast radiography,and determinereasonable method and limit requirements according to the clinical requirements and the determination results of the samples,so as to provide scientific basis for the quality control of aerogenic agent for double contrast radiography.Methods:Sodium bicarbonate,citric acid and sodium salt were identified by the chemical reaction.The gas production was measured by carbon dioxide gas generator.The method and limit requirements of the time and volume of gas production were determined,according to the clinical needs,combined with the sample measurement results.The reasonable determination method and limit requirements of loss on drying was compared and determined.The microbial limit determination method was determined,and the limits of dispersion,particle size and weight variation were determined.HPLC method was used for the determination of citric acid.The chromatographic column was Phenomenex-C18column(250 mm×4.6 mm,5μm).The mobile phase was methanol-0.2%phosphoric acid(5∶95),the flow rate was 0.8 mL·min^(-1),the detection wavelength was 215 nm,the column temperature was 25℃,and the injection volume was 10μL.Results:The identification reactions were specific and negative without interference.The volume of gas production should not be less than 360 mL,and the gas production time should be within 2 min.The weight loss of drying was determined by vacuum drying method at room temperature,and the limit requirement was no more than 0.2%.The method for microbial limit test was determined and the methodological validation was completed.The test methods for dispersion,particle size and weight variation were consistent with that in Chinese Pharmacopoeia.The linear range of citric acid was 1.6258-3.7936 mg·mL^(-1)(r=0.9999).The limit of quantification for citric acid was 10.84μg·mL^(-1).The RSDs of precision and repeatability tests were less than 1.5%(n=9).The average recovery of citric acid was 100.2%with the RSD of 1.8%(n=9).The determination results of citric acid in 3 batches of samples were 42.7%,42.8%and 41.5%respectively.Conclusion:The items of the drug quality standard established in this study are comprehensive,the methods are feasible and the limits are reasonable,and it can be used for the quality control of aerogenic agent for double contrast radiography.