用HPLC-MS/MS法测定人血浆中尼可地尔浓度  

Concentration of nicorandil in human plasma was determined by HPLC-MS/MS

作　　者：陈朝丽 王建欣[1] 杨兰 张娜娜 史凌雪 段立广[1] 安绯悦 伦杨 王佳琪 闫宇航 周春华 CHEN Chao-li;WANG Jian-xin;YANG Lan;ZHANG Na-na;SHI Ling-xue;DUAN Li-guang;AN Fei-yue;LUN Yang;WANG Jia-qi;YAN Yu-hang;ZHOU Chun-hua(Department of Clinical Pharmacy,The First Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei Province,China;The Technology Innovation Center for Artificial Intelligence in Clinical Pharmacy of Hebei Province,Shijiazhuang 050000,Hebei Province,China)

机构地区：[1]河北医科大学第一医院临床药学部,河北石家庄050000 [2]河北省人工智能临床药学技术创新中心,河北石家庄050000

出　　处：《中国临床药理学杂志》2025年第5期712-716,共5页The Chinese Journal of Clinical Pharmacology

摘　　要：目的建立测定人血浆中尼可地尔浓度的高效液相色谱-质谱(HPLC-MS/MS)法,并用于健康受试者的药代动力学研究。方法人血浆样品经乙腈萃取预处理。色谱柱:Acquity HPLC BEH C18(1.7μm,2.1 mm×50.0 mm),流动相:甲醇(含0.1%甲酸)-5 mmoL·L^(-1)乙酸铵(含0.1%甲酸)。流速:0.2 mL·min^(-1),柱温:40℃,进样量:5μL。梯度洗脱,电喷雾离子源,多反应监测,正离子扫描,内标为尼可地尔-d4同位素。考察该方法的专属性、标准曲线与定量下限、残留效应和稀释可靠性、精密度与回收率、基质效应、稳定性。结果建立的方法专属性好,尼可地尔在0.2~200.0 ng·mL^(-1)线性关系良好,其标准曲线为y=1.08×10^(-1)x+2.66×10^(-2)(r=0.9997),定量下限为0.2 ng·mL^(-1),无残留效应,稀释后结果可靠,质控样品批内和批间精密度分别为0.64%~8.70%和0.91%~8.70%,批内和批间的准确度分别在100.00%~115.00%和98.00%~115.00%。尼可地尔在低、中、高质控浓度下的提取回收率为92.78%~95.35%,无明显基质效应,稳定性良好。结论该方法专属性高、准确度好、稳定、可重复、操作简单,可用于测定尼可地尔血浆中药物浓度。Objective To establish a high performance liquid chromatography-mass spectrometry(HPLC-MS/MS)method for the determination of nicorandil concentrations in human plasma and for pharmacokinetic studies in healthy subjects.Methods Human plasma samples were pretreated with acetonitrile extraction.Chromatographic cdumn:Acquity HPLC BEH C_(18)(1.7μm,2.1 mm×50.0 mm),mobile phase:methanol(0.1%formic acid)-5 mmoL·L^(-1)ammonium acetate(with 0.1%formic acid).Flow rate:0.2 mL·min^(-1),column temperature:40℃,injection volume:5μL.Gradient elution,electrospray ion source,multiple reaction monitoring,positive ion scanning,nicorandil-d4 isotope as internal standard.The specificity of the method,the standard curve and the lower limit of quantification,the carryover effect and dilution reliability,the precision and recovery,the matrix effect,and the stability of the method were investigated.Results The specificity of the established method was good,nicorandil had a good linear relationship between 0.2-200.0 ng·mL^(-1),the standard curve wasy=1.08×10^(-1)x+2.66×10^(-2)(r=0.9997),the lower limit of quantification was 0.2 ng·mL^(-1),there was no residual effect,the dilution results were reliable,and the intra-day and inter-day precision of quality control samples were 0.64%-8.70%and 0.91%-8.70%,respectively.The intra-day and inter-day accuracy were 100.00%-115.00%and 98.00%-115.00%,respectively.The extraction recoveries of nicorandil at low,medium and high quality control concentrations were92.78%-95.35%,with no obvious matrix effect and good stability.Conclusion This method is highly specific,accurate,stable,reproducible,and simple to operate,and can be used to determine the concentration of drug in plasma of nicorandil.

关 键 词：尼可地尔 高效液相色谱-质谱法 血药浓度 药代动力学 

分 类 号：R972[医药卫生—药品]