用高效液相色谱-同位素稀释质谱法测定川崎病患儿血浆中阿司匹林和水杨酸的药物浓度
Determination of aspirin and salicylic acid of children with Kawasaki disease by HPLC-IDMS
马英华 1赵宜乐 1秦亚彬 1张英谦2
作者信息
- 1. 河北省儿童医院药学部,河北石家庄 050031
- 2. 河北省儿童医院心内科,河北石家庄 050031
- 折叠
摘要
目的 建立高效液相色谱-同位素稀释质谱(HPLC-IDMS)法测定川崎病患儿血浆中阿司匹林(ASP)和水杨酸(SA)浓度的方法.方法 血浆样品经有机溶剂沉淀蛋白后,分别以ASP-D4和SA-D4为内标,采用Phenomenex Kinetex® XB C18 色谱柱(2.6 mm ×50.0 mm,3.0 μm),以 0.1％甲酸-水(A)和乙腈(B)作为流动相进行梯度洗脱,流速为0.5 mL·min-1,进样量为6 μL.质谱检测方式为负离子模式,多反应监测扫描.结果 ASP在1.02～4 000 ng·mL-1线性关系良好(r2=0.995 4),定量下限(LLOQ)为1.02 ng·mL-1.SA在1.28～5 000 ng·mL-1线性关系良好(r2=0.998 5),LLOQ 为 1.28 ng·mL-1.准确度、精密度、基质效应和稳定性均符合《中国药典》(2020年版)规定.结论 该方法操作简便快速稳定,灵敏度专属性高,可用于ASP和SA在川崎病患儿中的治疗药物监测和群体药代动力学-药效学研究.
Abstract
Objective To establish a method for determination of aspirin(ASP)and salicylic acid(SA)in plasma of children with kawasaki disease by high performance liquid chromatography-isotope dilution mass spectrometry(HPLC-IDMS).Methods The samples were pre-treated by precipitation protein method with organic solvent.ASP-D4 and SA-D4 were used as isotope internal standards.Chromatographic column:Phenomenex Kinetex® XB C18(2.6 mm × 50.0 mm,3.0μm);flow phase:0.1％formic acid-water(A)and acetonitrile(B),gradient elution;flow speed:0.5 mL·min-1;injection volume:6 μL.The detection method of mass spectrometry was negative ion mode,multireaction monitoring mode for quantitative analysis.Results The linear range of aspirin was 1.02-4 000 ng·mL-1(r2=0.995 4),and lower limit of quantification(LLOQ)was 1.02 ng·mL-1.The linear range of salicylic acid was 1.28-5 000 ng·mL-1(r2=0.998 5),and LLOQ was 1.28 ng·mL-1.Accuracy,precision,matrix effect and stability were in line with the provisions of Chinese Pharmacopoeia(2020 edition).Conclusion This study determined the blood concentration of aspirin and salicylic acid in children with HPLC-IDMS,which is rapid,simple,stable,economical,and high specificity.It can be applied to therapeutic drug monitoring of aspirin and salicylic acid in clinical children with kawasaki disease.
关键词
阿司匹林/水杨酸/高效液相色谱-同位素稀释质谱法/同位素内标/治疗药物监测Key words
aspirin/salicylic acid/high performance liquid chromatography-isotope dilution mass spectrometry/isotope internal standards/therapeutic drug monitoring引用本文复制引用
基金项目
河北省重点研发计划卫生健康创新专项(22377729D)
出版年
2024
国家科技期刊平台
NSTL
万方数据