摘要
目的:建立HPLC法测定二甲双胍格列本脲片(Ⅱ)中格列本脲的有关物质。方法:色谱柱为C8柱(250 mm×4.6 mm,5μm),流动相A为pH 3.5的磷酸二氢铵溶液(取磷酸二氢铵1.725 g,加水300 mL溶解,用磷酸调节pH至3.5±0.05),流动相B为乙腈,梯度洗脱,流速为1.0 mL·min^-1,柱温为40℃,检测波长为230 nm。结果:格列本脲与已知杂质及强制破坏产生的降解产物均分离良好;格列本脲杂质Ⅰ、格列本脲杂质Ⅱ、格列本脲杂质B、格列本脲杂质C、格列本脲杂质D、格列本脲杂质E和格列本脲的定量下限分别为0.037、0.016、0.021、0.074、0.049、0.073和0.049μg·mL^-1,检测下限分别为0.011、0.0047、0.0062、0.022、0.015、0.022和0.015μg·mL^-1;格列本脲杂质Ⅰ、Ⅱ、B、C、D、E和格列本脲的质量浓度分别在0.03743~2.2455μg·mL^-1(r=0.9999)、0.01562~0.7808μg·mL^-1(r=1.000)、0.02076~0.7785μg·mL^-1(r=1.000)、0.07369~0.7369μg·mL^-1(r=0.9999)、0.04930~0.7395μg·mL^-1(r=0.9999)、0.07328~0.7328μg·mL^-1(r=0.9999)和0.05149~0.3862μg·mL^-1(r=0.9997)范围内与峰面积呈良好的线性关系;杂质Ⅰ、Ⅱ、B、C、D、E低、中、高3种浓度的平均回收率(n=9)分别为106.1%、102.6%、101.0%、100.0%、101.3%和99.0%。3批样品有关物质测定结果显示,各已知杂质的含量均低于0.2%,其他最大单个杂质的含量均低于0.1%,除杂质Ⅰ外,杂质总量均低于0.5%。结论:本方法可以用于二甲双胍格列本脲片(Ⅱ)中格列本脲的有关物质测定。
Objective:To establish an HPLC method for the determination of related substances of glyburide in glyburide and metformin hydrochloride tablets(Ⅱ).Methods:C8(250 mm×4.6 mm,5μm)column was adopted in this study,and the mobile phase A was monobasic ammonium phosphate buffer solution(dissolve 1.725 g of monobasic ammonium phosphate in 300 mL of water,and adjust to pH 3.5±0.05 with phosphoric acid);and the mobile phase B was acetonitrile with gradient elution at the flow rate of 1.0 mL·min^-1.The column temperature was 40℃,and the detection wavelength was 230 nm.Results:Glyburide was well separated from the known impurities and the forced degradation products.The limits of quantitation were 0.037,0.016,0.021,0.074,0.049,0.073,0.049μg·mL^-1 for glyburide impurityⅠglyburide impurity,Ⅱglyburide impurity,B glyburide impurity,C glyburide impurity,D glyburide impurity,E and glyburide,respectively.The limits of detection were 0.011,0.0047,0.0062,0.022,0.015,0.022 and 0.015μg·mL^-1.There was a good linearity separately over the ranges 0.03743-2.2455μg·mL^-1(r=0.9999)of glyburide related impurityⅠ,0.01562-0.7808μg·mL^-1(r=1.000)of glyburide related impurityⅡ,0.02076-0.7785μg·mL^-1(r=1.000)of glyburide related impurity B,0.07369-0.7369μg·mL^-1(r=0.9999)of glyburide related impurity C,0.04930-0.7395μg·mL^-1(r=0.9999)of glyburide related impurity D,0.07328-0.7328μg·mL^-1(r=0.9999)of glyburide related impurity E,0.05149-0.3862μg·mL^-1(r=0.9997)of glyburide.The average recovery rates(n=9)were 106.1%,102.6%,101.0%,100.0%,101.3%and 99.0%at the concentration level of low,medium and high concentrations,respectively.The results of related substances in the three batches of samples showed that the content of each known impurities was less than 0.2%,and the content of the other single impurities was less than 0.1%.Except for impurityⅠ,the content of totol impurities was less than 0.5%.Conclusion:The method is suitable for the determination of related substances of glyburide in glyburide and metformin hydrochloride tablets(Ⅱ).
作者
史芳
连亚飞
秦甲
SHI Fang;LIAN Ya-fei;QIN Jia(Zhongshuai Pharmaceutical SCI&TECH CO.,Ltd.,Zhengzhou 450001,China)
出处
《药物分析杂志》
CAS
CSCD
北大核心
2019年第11期2051-2058,共8页
Chinese Journal of Pharmaceutical Analysis
