柱前衍生化液质联用法测定氯乙酰氯试剂中的乙酰氯和二氯乙酰氯  

Determination of Acetyl chloride and Dichloroacetyl Chloride in Chloroacetyl Chloride by Pre-column Derivatization Ultra Performance Liquid Chromatography-tandem Mass Spectrometry

作　　者：邵方娴 何燕琳 芦丽 黄朝瑜 王晨 严菲 SHAO Fang-xian;HE Yan-lin;LU Li;HUANG Chao-yu;WANG Chen;YAN Fei(Jiangsu Institute for Food and Drug Control,Nanjing 210019,China;Department of Pharmaceutical Analysis,China Pharmaceutical University,Nanjing 210009,China;Key Laboratory of Chemical Impurity Spectrometry,National Medical Products Administration,Nanjing 210019,China)

机构地区：[1]江苏省食品药品监督检验研究院,江苏南京210019 [2]中国药科大学药物分析教研室,江苏南京210009 [3]国家药品监督管理局化学药杂质谱重点实验室,江苏南京210019

出　　处：《化学试剂》2024年第4期102-107,共6页Chemical Reagents

基　　金：江苏省药品监督管理局科研计划项目(202209)。

摘　　要：建立了柱前衍生化超高效液相色谱-三重四级杆联用(UPLC-MS/MS)法同时测定酰化试剂氯乙酰氯中的杂质乙酰氯和二氯乙酰氯的含量。以苯胺作衍生化试剂,采用Poroshell 120 Aq-C18(150 mm×2.1 mm, 2.7μm)为色谱柱,0.1%(V/V)甲酸水和乙腈为流动相,梯度洗脱,流速为0.3 mL/min。在电喷雾离子源(ESI),正离子监测下,采用多反应监测扫描(MRM)模式。乙酰氯和二氯乙酰氯分别在0.5~50 ng/mL和5~500 ng/mL范围内线性关系良好(R^(2)≥0.998 6),定量限为0.5和5 ng/mL,检出限为0.2和2 ng/mL;回收率(n=3)为90.8%~103.1%和92.5%~108.7%,RSD为1.4%~6.6%和0.9%~3.8%。衍生化产物室温放置24 h内稳定。方法准确可靠,简便高效,可用于氯乙酰氯中乙酰氯和二氯乙酰氯的同时检测。A pre-column derivatization ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS)method was developed for the simultaneous determination of acetyl chloride and dichloroacetyl chloride in the acylating agent chloroacetyl chloride.The target compounds were derivatized with aniline.Separation was carried out using an Agilent Poroshell 120 Aq-C18 column(150 mm×2.1 mm,2.7μm).The mobile phase consisted of a gradient elution of 0.1%(V/V)formic acid aqueous solution and acetonitrile.The flow rate was set at 0.3 mL/min.Detection of the target compounds was performed using electrospray ionization(ESI)in positive ionization mode under multiple reaction monitoring(MRM)mode.The established method exhibited good linearity within the concentration ranges of 0.5 to 50 ng/mL for acetyl chloride and 5 to 500 ng/mL for dichloroacetyl chloride,with correlation coefficients(R^(2))equal to or greater than 0.9986.The lower limits of quantitation were determined to be 0.5 and 5 ng/mL for acetyl chloride and dichloroacetyl chloride,respectively,while the lower limits of detection were found to be 0.2 and 2 ng/mL.The method demonstrated satisfactory accuracy,with ranges of 90.8%to 93.5%and 92.5%to 108.7%,and precision,with ranges of 1.4%to 6.6%and 0.9%to 3.8%,for acetyl chloride and dichloroacetyl chloride,respectively.The stability of the derivatives was confirmed for a period of 24 hours.The established pre-column derivatization UPLC-MS/MS method in this study is accurate and suitable for the determination of acetyl chloride and dichloroacetyl chloride in chloroacetyl chloride.

关 键 词：氯乙酰氯杂质检测 乙酰氯 二氯乙酰氯 柱前衍生化 超高效液相色谱-串联质谱法(UPLC-MS/MS) 

分 类 号：R917[医药卫生—药物分析学]