摘要
目的 建立了一种高效液相色谱-三重四极杆串联质谱法,对氯沙坦钾原料药中遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸(NMBA)进行测定。方法 色谱柱为岛津Shim-pack XR-ODSⅡ色谱柱(2.0 mm×150 mm, 2.2 μm),流动相为0.1%甲酸水溶液(A)和甲醇(B),进行梯度洗脱,流速0.3 mL·min-1,柱温为40 ℃,采用ESI离子化-三重四极杆质谱多反应监测(MRM)正离子模式检测,碰撞电压分别为-11,-13和-13 V,碰撞气氩气270 kPa,NMBA的离子对分别为m/z 147.15→117.10, 147.15→87.10和147.15→44.10。结果 该方法中NMBA在1~100 ng·mL-1内线性关系良好,日内和日间的保留时间和峰面积的重复性良好(RSD均小于1.10%,n=6和n=18),低、中、高3个浓度的平均回收率在94.40%~98.04%之间。结论 本方法简单方便,可快速有效的对氯沙坦钾原料药中NMBA进行限度检查并实现定量分析。
Abstract
OBJECTIVE To establish a method to determine the genotoxic impurity, N-nitroso-N-methyl-4-aminobytyric acid, in losartan potassium using high performance liquid chromatography triple quadrupole mass spectrometry (HPLC-MS/MS). METHODS The method was developed by using Shimadzu Shim-pack XR-ODS II column (2.0 mm×150 mm, 2.2 μm). Time program was conducted with mobile phase consisting of water (0.1% formic acid, A) and methanol (B). The flow rate was 0.3 mL·min-1, and the column oven temperature was maintained at 40 ℃. The samples were ionized by electrospray ionization (ESI) with multi reaction monitoring (MRM) data acquisition mode. The collision energies were -11, -13, and -13 V, CID gas was argon with pressure of 270 kPa.3 pairs of precursor, and product ions (m/z) of NMBA were 147.15→117.10, 147.15→87.10, and 147.15→44.10, respectively. RESULTS The genotoxic impurity NMBA showed linearity between 1 and 100 ng·mL-1 with correlation coefficient of 0.999 9. The intra-day and inter-day repeatability was examined by relative standard deviations (RSDs) of retention time and peak area (RSD<1.10%, n=6 for intra-day repeatability and n=18 for inter-day repeatability). The accuracy was examined by percent recovery at three concentration levels, and the average percent recovery was between 94.40% and 98.04%. CONCLUSION The established LC-MS/MS method is efficient for limit test and quantitation of NMBA in losartan potassium bulk drug.
关键词
液相色谱-串联质谱法 /
氯沙坦钾 /
遗传毒性杂质 /
N-亚硝基-N-甲基-4-氨基丁酸 /
限度检查
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Key words
HPLC-MS/MS /
losartan potassium /
genotoxic impurity /
N-nitroso-N-methyl-4-aminobytyric acid /
limit test
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邹韵, 孙丽鹏, 李晓东, 滨田尚树.
高效液相色谱串联质谱法测定氯沙坦钾中的遗传毒性杂质N-亚硝基-N-甲基-4-氨基丁酸[J]. 中国药学杂志, 2020, 55(3): 228-232 https://doi.org/10.11669/cpj.2020.03.012
ZOU Yun, SUN Li-peng, LI Xiao-dong, HAMADA Naoki.
Determination of N-Nitroso-N-Methyl-4-Aminobutyric Acid in Losartan Potassium Using High Performance Liquid Chromatography Triple Quadrupole Mass Spectrometry[J]. Chinese Pharmaceutical Journal, 2020, 55(3): 228-232 https://doi.org/10.11669/cpj.2020.03.012
中图分类号：
R284
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参考文献
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