厄贝沙坦及其复方制剂中痕量杂质N-亚硝基-N-甲基-4-氨基丁酸残留方法学研究

The residual research method of trace impurity NMBA inirbesartan and its compound preparation

采用超高效液相色谱-三重四级杆质谱(UPLC-MS/MS)建立厄贝沙坦及其复方制剂中N-亚硝基-N-甲基-4-氨基丁酸(NMBA)的测定方法。采用Waters ACQUITY UPLC○RHSS T3色谱柱进行分离,以0.005 mol/L甲酸铵(用甲酸调pH值至3.0)为流动相A,甲醇为流动相B,梯度洗脱,质谱检测器,流速为0.3 mL/min。结果显示NMBA的线性范围为0.156 6~3.132 6 ng/mL,相关系数r>0.99,方法检出限浓度为0.047 0 ng/mL(相当于样品浓度0.01μg/g),定量限浓度为0.156 6 ng/mL(相当于样品浓度0.03μg/g),样品加标回收率在80%~130%。说明该方法可以快速、简便、灵敏、准确地测定厄贝沙坦及其复方制剂中NMBA含量。

To determine the genotoxic impurity N-nitroso-N-methyl-4-amimobutyric acid(NMBA) in Irbesartan and its compound preparation by Ultra Performance Liquid Chromatography-triple quadrupole mass spectrometer.The separation was carried out on a Waters ACQUITY UPLC HSS T3 column with the mobile phase consisting of 0.005 mol/L ammonium formate(pH3.0) was used as the mobile phase A and methanol as the mobile phase B.Gradient elution was used.The detector was mass spectrum.The flow rate was 0.3 mL/min.The result showed the linear range was 0.156 6-3.132 6 ng·mL^(-1) with the correlation coefficients above 0.99.The limit of detection was 0.047 0 ng·mL^(-1)(Equivalent to 0.01 ppm of sample concentration),and the limit of quantification was 0.156 6 ng·mL^(-1)(equivalent to 0.03 ppm of sample concentration),the recoveries were between 80%~130%.The method was rapid,simple,sensitive and accurate for the quantitative determination of NMBA inIrbesartan and its Compound Preparation.