缬沙坦中N-亚硝基-N-甲基-4-氨基丁酸的高效液相色谱-串联质谱法测定方法的建立及评价

Establishment and Evaluation of High Performance Liquid Chromatography-Mass Spectrometry/Mass Spectrometry for Determination of N-nitroso-N-methyl-4-aminobutyric Acid in Valsartan

目的建立缬沙坦中N-亚硝基-N-甲基-4-氨基丁酸(NMBA)的高效液相色谱-串联质谱法(HPLC-MS/MS)测定方法。方法采用梯度洗脱法,以0.1%甲酸的水溶液为流动相A,0.1%甲酸的甲醇溶液为流动相B进行梯度洗脱,NMBA-D3为内标采用HPLC-MS/MS法测定缬沙坦中NMBA含量。结果空白溶剂对NMBA及NMBA-D3检测无干扰,NMBA及NMBA-D3互不干扰。NMBA的线性范围均为3.0~100.0 ng/ml,r=0.9992。检测限和定量限分别为1 ng/ml和3 ng/ml,进样精密度相对标准偏差(RSD)为2.0%,低、中、高3个浓度加样回收率在100%左右,且平行性良好。该方法耐用性良好。结论该方法简单方便、快速易行,可作为控制缬沙坦中NMBA含量的有效检测方法。

Objective To establish a HPLC-MS/MS method for the determination of N-nitroso-N-methyl-4-aminobutyric acid(NMBA)in Valsartan.Methods The gradient elution method was adopted,with 0.1%formic acid in water as mobile phase A,0.1%formic acid in methanol as mobile phase B for gradient elution,and NMBA-D3 as the internal standard for the determination of NMBA in valsartan.Results The blank solvent did not interfere with the detection of NMBA and NMBA-D3,and NMBA and NMBA-D3 did not interfere with each other.The linear range of NMBA was 3.0-100.0 ng/ml,r=0.9992.The detection limit and quantification limit were 1 ng/ml and 3 ng/ml,respectively,the relative standard deviation(RSD)of injection precision was 2.0%,and the recovery rate of the three concentrations of low,medium and high was about 100%,with good parallel nature.This method had good durability.Conclusion The method is simple,convenient,fast and easy to implement,and can be used as an effective detection method to control the NMBA content in valsartan.