摘要
目的优化多潘立酮片有关物质检测方法,并与原研药进行有关物质一致性评价研究。方法采用资生堂MG C18(4.6 mm×250 mm,5μm)色谱柱,流动相为甲醇-0.5%乙酸铵溶液-0.5%乙酸铵溶液(用冰乙酸调节pH值为4.5),梯度洗脱,流速为1.0 mL·min^(-1),检测波长为285 nm,柱温为35℃。已知杂质为加校正因子的自身对照法,未知杂质为不加校正因子的自身对照法。取62批样品置于温度40℃、相对湿度75%条件下放置6个月,分别于第1、3、6个月取样测定有关物质。结果在建立的色谱条件下,主峰与已知杂质峰及其他未知杂质峰分离良好,各已知杂质的线性关系良好,回收率为93.15%~107.53%。62批次样品中,有42批次样品中检出基因毒性杂质1-(3-氯丙基)-1,3二氢苯并咪唑-2-酮(杂质G),其他单个杂质量均≤0.16%,杂质总量≤0.45%。在加速6个月过程中,所有样品杂质A、杂质C均有增大趋势,其他杂质无明显变化。结论该方法灵敏度高,专属性好,可用于多潘立酮片中有关物质的分析研究。
Objective To optimize the determination of related substances in domperidone tablets,and compare the consistency of related substances with the original preparation.Methods The separation was performed on Shiseido MG C18(4.6 mm×250 mm,5μm)column with gradient elution of the mobile phase consisting of methanol-0.5%ammonium acetate solution-0.5%ammonium acetate solution(pH 4.5).The flow rate was 1.0 mL·min^(-1),the detection wavelength was 285 nm,and the column temperature was 35℃.The known impurities was quantitatively determined by main component self-comparing with relative response factors.The unknown impurities were determined by main component self-comparing method without relative response factor.The reference preparations and self-developed preparations were placed at 40℃and 75%relative humidity for 6 months,and samples were taken in the 1st,3rd and 6th month to determine the content of related substances.Results The main peak was well separated from the known impurity peaks and other degraded impurity peaks,and the linearity of the known impurities was good.The recoveries of the known impurities were between 93.15%and 107.53%.Genotoxic impurity G was detected in 42 of the 62 sample batches.Other single impurity content was no more than 0.16%and the content of total impurity was no more than 0.45%.In the process of 6 months acceleration impurity A and impurity C increased,while other impurities had no obvious change.Conclusion The method is sensitive and specific,which can be used for the study of related substances in domperidone tablets and quality consistency evaluation.
作者
王发
李继
杜玮
妙苗
刘雪峰
乔荣霞
WANG Fa;LI Ji;DU Wei;MIAO Miao;LIU Xue-feng;QIAO Rong-xia(Shaanxi Institute for Food and Drug Control,Xi’an 710065)
出处
《中南药学》
2023年第9期2454-2458,共5页
Central South Pharmacy
基金
陕西省重点研发计划(No.2021SF-304)。
