米拉贝隆中3种降解杂质的UPLC测定
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摘要
建立了超高效液相色谱(UPLC)法测定米拉贝隆原料药中的3种降解杂质。采用Acquity UPLC BEH C_(18)色谱柱,以5 mmol/L庚烷磺酸钠溶液∶20 mmol/L磷酸二氢钾溶液(用磷酸调至pH 3.0)为流动相A,以乙腈为流动相B,线性梯度洗脱,检测波长220 nm。采用加校正因子的主成分自身对照法,以米拉贝隆为参照物,分别测定其与降解杂质之间的相对保留时间(RRT)及相对校正因子(RCF),以RCF对米拉贝隆中的3种降解杂质进行定量分析,并与标准曲线法测定结果比较,以验证方法的准确性。3种降解杂质的RRT分别为0.53、0.78和1.22;RCF分别为1.38、1.63和1.25;RCF法与标准曲线法测定结果无显著性差异。本方法能够准确测定米拉贝隆原料药中的3种降解杂质。
A UPLC method was established for the quantification of three degradation products in mirabegron. An Acquity UPLC BEH C_(18) column was used, with the mobile phase A of 5 mmol/L sodium 1-heptanesulfonate solution∶20 mmol/L potassium dihydrogen phosphate solution(adjusted to pH 3.0 with phosphoric acid), and the mobile phase B of acetonitrile, for the linear gradient elution, at the detection wavelength of 220 nm. Corrected peak areas of impurities were compared with that produced by the main peak of a diluted solution of mirabegron. The relative retention times(RRTs) and the relative correction factors(RCFs) of degradation products were determined using mirabegron as the reference. The results obtained by the proposed method were compared with those obtained by the regression equation method to verify the method accuracy. The RRTs of three degradation products to mirabegron were 0.53, 0.78 and 1.22, and their RCFs were 1.38, 1.63 and 1.25, respectively. There were no significant differences in the results between the method with RCFs and the regression equation method. The UPLC method with RCFs can be applied to determine the degradation products in mirabegron.
A UPLC method was established for the quantification of three degradation products in mirabegron. An Acquity UPLC BEH C_(18) column was used, with the mobile phase A of 5 mmol/L sodium 1-heptanesulfonate solution∶20 mmol/L potassium dihydrogen phosphate solution(adjusted to pH 3.0 with phosphoric acid), and the mobile phase B of acetonitrile, for the linear gradient elution, at the detection wavelength of 220 nm. Corrected peak areas of impurities were compared with that produced by the main peak of a diluted solution of mirabegron. The relative retention times(RRTs) and the relative correction factors(RCFs) of degradation products were determined using mirabegron as the reference. The results obtained by the proposed method were compared with those obtained by the regression equation method to verify the method accuracy. The RRTs of three degradation products to mirabegron were 0.53, 0.78 and 1.22, and their RCFs were 1.38, 1.63 and 1.25, respectively. There were no significant differences in the results between the method with RCFs and the regression equation method. The UPLC method with RCFs can be applied to determine the degradation products in mirabegron.
引文
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[3]范鸣.膀胱过度活动症治疗药Mirabegron[J].药学进展,2012,36(3):133—135.
[4]毛龙飞,苑李双,颜茗彦,等.米拉贝隆的合成研究[J].化学研究与应用,2016,28(4):521—524.
[5]章磊,谭支敏,焦慧荣,等.米拉贝隆有关物质的合成[J].中国医药工业杂志,2014,45(1):9—12.
[6]丁逸梅,浦雨伟,吴娟,等.米拉贝隆有关物质的HPLC法测定[J].药物分析杂志,2016,36(8):1439—1445.
[7]王亚男,毋艳,靳香菊,等.米拉贝隆原料药主要降解产物的鉴定研究[J].药物分析杂志,2016,36(10):1841—1846.
[8]郑亚东,和龙,贾志丹,等.米拉贝隆和去羟基米拉贝隆的合成[J].山东化工,2016,45(1):3—5.