摘要
目的 建立托拉塞米片中7种主要有关物质的HPLC测定法.方法 从原料药中分离尚未建立标准的2种主要杂质F和G,通过1H-NMR进行结构确认;在此基础上采用HPLC法建立托拉塞米片中7种主要杂质(杂质A、B、C、D、E、F、G)的测定方法.色谱柱为ACE C18柱(100mm×4.6mm,3μm);流动相为0.02 mol/L磷酸二氢钾溶液(磷酸调pH至3.5)-甲醇,梯度洗脱;流速为0.8 mL/min;柱温为30 ℃;检测波长为288 nm;进样体积为20μL.结果 在该色谱条件下,可以同时检测到这7种杂质,各杂质峰的分离度均大于1.5.其定量限分别为0.083 5、0.009 9、0.020 4、0.084 3、0.024 3、0.025 5、0.039 8 μg/mL,检测限分别为 0.025 1,0.003 9,0.006 1,0.025 3,0.007 3,0.007 7,0.012 0 μg/mL,线性范围分别为 0.334 0～1.336 0、0.794 6～3.178 2、0.326 4～1.305 6、0.337 2～1.348 8、0.323 8～1.295 0、0.430 3～1.021 0、0.318 7～0.956 1 μg/mL.各杂质在48 h内溶液稳定性良好,峰面积RSD＜3.0％(n=7).低、中、高三个浓度的杂质加样回收率均在90.6％～106.6％范围内(n=3).结论 本研究提升了托拉塞米片质量控制方法,且方法简便、灵敏,重现性和耐用性好,能够用于托拉塞米片的质量控制.
Abstract
Objective To establish a HPLC method for the determination of 7 main related substances in torasemide tablets.Methods Two major impurities F and G,which have not yet been established as standard,were separated from the API and the structure was confirmed by 1H-NMR.On this basis,the impurity content of A,B,C,D,E,F,G in torasemide tablets was determiened by HPLC.An HPLC method was adopted with ACE C18 column(100 mm× 4.6 mm,3 μm);the mobile phase was 0.02 mol/L KDP(phosphoric acid adjusted pH to 3.5)-methanol,gradient elution.The flow rate was 0.8 mL/min;the column temperature was 30 ℃;the detection wavelength is 288 nm;the injection volume was 20 μL.Results Under this chromatographic condition,7 impurities can be detected at the same time,and each impurity was well separated from torasemide,and the separation degree was greater than 1.5.The limits of quantitation were 0.083 5,0.009 9,0.020 4,0.084 3,0.024 3,0.025 5,0.039 8 μg/mL;the limits of detection were 0.025 1,0.003 9,0.006 1,0.025 3,0.007 3,0.007 7,0.012 0 μg/mL.The linear ranges of them were 0.334 0-1.336 0,0.794 6-3.178 2,0.326 4-1.305 6,0.337 2-1.348 8,0.323 8-1.295 0,0.430 3-1.021 0,0.3187-0.9561 μg/mL.The solution stability of the impurities was good within 48 h,and the RSD of the peak area was less than 3.0％(n=7).The average recovery of low,medium and high recovery solutions was 90.6％～106.6％(n=3).Conclusion This study improved the quality control method of torasemi tablets and the method is simple,sensitive,reproducible and durable,and can be used for the quality control of quetiapine fumarate tablets.
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