UPLC-MS/MS法测定利奈唑胺及其中间体(S)-N-(2-乙酰氧基-3-氯丙基)乙酰胺中的遗传毒性杂质(S)-1-氨基-3-氯-2-丙醇  

Determination of(S)-1-amino-3-chloro-2-propanol in linezolid and its intermediate[(2S)-1-acetamido-3-chloropropan-2-yl]acetate by UPLC-MS/MS

作　　者：刘峰 赵荣丽[2] 王璐 LIU Feng;ZHAO Rong-li;WANG Lu(Sichuan Institute for Drug Control,Chengdu 611731;Chengdu Institute of Biological Products Co.,Ltd.,Chengdu 610023)

机构地区：[1]四川省药品检验研究院,成都611731 [2]成都生物制品研究所有限责任公司,成都610023

出　　处：《中南药学》2021年第7期1439-1443,共5页Central South Pharmacy

摘　　要：目的建立液质联用色谱法(UPLC-MS/MS)同时测定利奈唑胺及其中间体(S)-N-(2-乙酰氧基-3-氯丙基)乙酰胺中的基因毒性杂质(S)-1-氨基-3-氯-2-丙醇。方法采用Agilent Poroshell 120 EC-C_(18)色谱柱,流动相为0.1%甲酸水溶液-0.1%甲酸甲醇溶液(梯度洗脱),流速为0.3 mL·min^(-1),柱温为35℃,进样量为2μL,电喷雾离子源,正离子模式,多反应监测模式(MRM)测定,定量离子对为质荷比(m/z)110.0→91.9,定性离子对为质荷比(m/z)110.0→56.1。结果(S)-1-氨基-3-氯-2-丙醇在0.836~208.989 ng·mL^(-1)范围内线性关系良好(r=0.9996),检测限为0.279 ng·mL^(-1),定量限为0.774 ng·mL^(-1),利奈唑胺中该杂质平均加样回收率在96.6%~97.6%(RSD<2%),中间体中该杂质平均加样回收率在101.6%~105.6%(RSD<2%)。3批利奈唑胺中均未检出该杂质,3批中间体中该杂质含量均小于0.05%。结论本法灵敏、可靠,可用于利奈唑胺及其起始原料(S)-N-(2-乙酰氧基-3-氯丙基)乙酰胺中基因毒性杂质(S)-1-氨基-3-氯-2-丙醇的测定。Objective To establish an UPLC-MS/MS method to determine the genotoxic impurity of(S)-1-amino-3-chloro-2-propanol in linezolid and its intermediate[(2S)-1-acetamido-3-chloropropan-2-yl]acetate.Methods The separation was performed on Agilent Poroshell 120 EC-C_(18) column with the mobile phase consisting of 0.1%formic acid water solution-0.1%formic acid methanol solution(gradient elution)at the flow rate of 0.3 mL·min^(-1).The column temperature was 35℃and the injection volume was 2μL.Electrospray ion source was used under positive mode in multiple reactions monitoring mode.The quantitative and qualitative ion pairs were m/z 110.0→91.9 and 110.0→56.1.Results(S)-1-amino-3-chloro-2-propanol showed good linearity at 0.836-208.989 ng·mL^(-1)(r=0.9996).The LOD of(S)-1-amino-3-chloro-2-propanol was 0.279 ng·mL^(-1),LOQ was 0.774 ng·mL^(-1).RSDs of precision,stability and reproducibility tests were all lower than 5%.The average recovery of(S)-1-amino-3-chloro-2-propanol in linezolid was at 96.6%~97.6%(RSD<2%),and in[(2S)-1-acetamido-3-chloropropan-2-yl]acetate was at 101.6%~105.6%(RSD<2%).The content of(S)-1-amino-3-chloro-2-propanol in 3 batches of linezolid was all not detected,and all below 0.05%in the 3 batches of[(2S)-1-acetamido-3-chloropropan-2-yl]acetate.Conclusion The method is sensitive and reliable,which can be used to determine(S)-1-amino-3-chloro-2-propanol in linezolid and its intermediate[(2S)-1-acetamido-3-chloropropan-2-yl]acetate.

关 键 词：利奈唑胺 (S)-N-(2-乙酰氧基-3-氯丙基)乙酰胺 液质联用色谱法 基因毒性杂质 (S)-1-氨基-3-氯-2-丙醇 

分 类 号：R927[医药卫生—药学]