Objective： To establish an UPLC-MS/MS analytical method for the determination of seven N-nitrosamines genotoxic impurities（ N-nitroso-dimethylamine,N-nitroso-N-methyl-4-aminobutyric acid,N-nitroso-diethylamine,N-nitroso-ethyl-isoprosylamine,N-nitroso-diisopropylamine,N-nitroso-dipropylamine and N-nitroso-dibutylamine） in losartan potassium and valsartan. Methods： The separation was performed on an Agilent InfinityLab Poroshell 120 SB-AQ（ 3.0 mm×150 mm,2.7 μm） column with the mobile phase consisting of 0.1% formic acid aqueous solution（mobile phase A） and methanol（ mobile phase B） by gradient elution at a flow rate of 0.5 mL·min-1 and the column temperature was 50 ℃. Another Agilent Poroshell 120 EC-C18（4.6 mm×50 mm,2.7 μm） column was installed between pump mixer and injector. Multiple reaction monitoring （MRM） was performed on a triple quadripole mass spectrometer equipped with a APCI source in positive mode. Results： In the test of losartan potassium,the calibration curve was linear for seven compounds in the range of 1-100 ng·mL-1,r>0.995. The recoveries（n=3）of low,middle,high adding concentrations were 79.1%- 108.8%. RSDs were 0.57%-4.8%;the limit of detection was 0.03-0.22 ng·mL-1,and the limit of quantification was 0.09-0.76 ng·mL-1. In the test of valsartan,the calibration curve was linear for seven compounds in the range of 1-100 ng·mL-1,with r>0.995. The recoveries（n=3） of low,middle,high added amounts were 81.0%- 105.7%. RSDs were 0.89%-4.1%. The limit of detection was 0.05-0.29 ng·mL-1,and the limit of quantification was 0.17-0.95 ng·mL-1. No impurities were detected in the samples. Conclusion： The method is sensitive, accurate,which is applicable for quantifications of seven N-nitrosamines genotoxic impurities in losartan potassium and valsarten. The method can provied a reference for the control of nitrosaminies impurities in chemical drugs.
YUAN Song, HUANG Hai-wei, YU Ying-jie, LIU Yang, HE Lan
. Determination of seven N-nitrosamines genotoxic impurities in losartan potassium and valsartan by UPLC-MS/MS*[J]. Chinese Journal of Pharmaceutical Analysis, 2021
, 41(7)
: 1218
-1225
.
DOI: 10.16155/j.0254-1793.2021.07.13
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