摘要
目的:建立高效液相色谱法测定盐酸左旋咪唑片的有关物质及含量。方法:有关物质检测采用Thermo Hypsil C18(100 mm×4.6 mm,3μm)色谱柱,以0.75%磷酸二氢铵溶液(用二异丙胺调节pH至7.0)-乙腈为流动相,梯度洗脱;含量测定采用InertSustain C18(150 mm×4.6 mm,5μm)色谱柱,以0.75%磷酸二氢铵溶液(用二异丙胺调节pH至7.0)-乙腈(70∶30)为流动相。流速均为1.0 mL·min^(-1),检测波长均为215 nm,进样体积均为10μL。结果:建立的有关物质检测方法能较好地分离盐酸左旋咪唑与5个已知杂质;已知杂质A、B、C、D、E质量浓度在10.87~25.37、11.62~27.10、12.38~28.90、30.89~72.07、12.41~28.95μg·mL-1的范围内与峰面积呈良好的线性关系(r>0.999),平均校正因子分别为1.6、1.4、2.6、1.2、2.4,平均回收率(n=9)分别为98.1%、99.0%、98.6%、100.1%和99.9%,RSD分别为0.63%、0.79%、0.92%、0.96%、0.33%。建立的含量测定方法能分离盐酸左旋咪唑与相邻杂质C;盐酸左旋咪唑质量浓度在0.1014~0.3043 mg·mL-1的范围内与峰面积呈良好的线性关系(r=0.9999);盐酸左旋咪唑的平均回收率(n=9)为100.2%,RSD=0.52%;盐酸左旋咪唑的定量限与检测限分别为0.076 ng和0.030 ng。采用建立的方法实际测定5家企业生产的10批样品,总杂质量为0.05%~0.62%,含量为99.5%~104.3%。结论:研究建立的盐酸左旋咪唑片的有关物质和含量测定的方法专属性强,结果准确度高,可用于盐酸左旋咪唑片中杂质的控制研究以及质量标准的提高。
Objective:To develop an HPLC method for the determination of related substances and assay of le⁃vamisole hydrochloride tablets.Methods:The chromatographic separation of related substances was performed on a Thermo Hypsil C18 column(100 mm×4.6 mm,3μm).A gradient elution was applied with a mobile phase composed of 0.75%monobasic ammonium phosphate solution(adjusted at pH 6.5 with diiopropylamine)and ace⁃tonitrile.The assay analytical column was packed with IntertSustain C18 column(150 mm×4.6 mm,5μm).The mobile phase was 70 volumes of 0.75%monobasic ammonium phosphate solution(adjusted at pH 7.0 with diio⁃propylamine)with 30 volumes of acetonitrile.The wavelength detection was set at 215 nm,the injection volumn was 10μL,and the flow rate was 1.0 mL·min^(-1).Results:Levamisole and its impurities were separated well by related substances HPLC method above.Impurities A,B,C,D,E showed the good linearities in the concentra⁃tion ranges of 10.87-25.37μg·mL-1,11.62-27.10μg·mL-1,12.38-28.90μg·mL-1,30.89-72.07μg·mL-1,12.41-28.95μg·mL-1(r>0.999).The average correction factors of impurities A,B,C,D,E determined by three columns and liquid chromatographies were 1.6,1.4,2.6,1.2,2.4,respectively,the recovery rates(n=9)were 98.1%,99.0%,98.6%,100.1%,99.9%and the RSDs were 0.63%,0.79%,0.92%,0.96%,0.33%.The separation of levamisole and impurity C was good by assay HPLC method.Levamisole showed the good linearity in the concentration range of 0.1014-0.3043 mg·mL-1(r=0.9999).The average recovery rate(n=9)of levamisole was 100.2%,RSD=0.52%.Ten batches levamisole hydrochlo⁃ride tablets from five domestic pharmaceutical enterprises were determined by the above related substances and assay HPLC method,the total impurities mass were 0.05%-0.62%,and the assays were 99.5%-104.3%.Conclusion:The established method is high selection and accurate.It is suitable applied for determination of related substances and assay of levamiole hydrochloride tablets.
作者
鲍实
赵亚萍
曹全胜
BAO Shi;ZHAO Ya-ping;CAO Quan-sheng(Hubei Institute for Drug Control,Wuhan 430075,China;Hubei Engineering Research Center for Drug Quality Control,Wuhan 430075,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2024年第4期705-713,共9页
Chinese Journal of Pharmaceutical Analysis
基金
2016年国家药典委员会药品标准提高课题(品种编号:化175)。
