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.
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.
马英华;赵宜乐;秦亚彬;张英谦
河北省儿童医院药学部,河北石家庄 050031河北省儿童医院心内科,河北石家庄 050031
药学
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
aspirin;salicylic acid;high performance liquid chromatography-isotope dilution mass spectrometry;isotope internal standards;therapeutic drug monitoring
《中国临床药理学杂志》 2024 (008)
1203-1207 / 5
河北省重点研发计划项目-卫生健康创新专项基金资助项目(22377729D)
10.13699/j.cnki.1001-6821.2024.08.024
评论