HPLC-MS法同时测定大鼠血浆中那格列奈及其主要代谢物M1  

The HPLC-MS method for simultaneous determination of nageleinai and its major metabolite M1 in rat plasma

作　　者：卞乐乐 潘静 郑永克 Bian Lele

机构地区：[1]浙江省温州市中心医院,325000

出　　处：《浙江临床医学》2024年第2期184-186,共3页Zhejiang Clinical Medical Journal

摘　　要：目的建立同时测定那格列奈及其主要代谢物M1的HPLC-MS方法。方法血浆样品经过乙酸乙酯萃取,以非那西丁为内标。色谱采用岛津C18柱(5μm,4.6 mm×250 mm)分离,流动相为0.1%甲酸溶液与乙腈,梯度洗脱,流速0.2 mL/min。质谱采用选择性离子监测(SIM)阳离子模式,检测对象[M+H]^(+)为:那格列奈318.2,代谢物M1334.1,非那西丁180.1。结果标准曲线线性范围为0.0625~8μg/mL那格列奈,M1为0.0313~4μg/mL。日内及日间准确度和精密度变异均<10%,血浆样品稳定性良好,提取回收率均>96%,基质效应<5%。结论本方法稳定性好、灵敏度高、重现性好,可应用于各类生物样本中那格列奈及其代谢物M1的生物等效性与药物代谢动力学研究。Objective To establish a HPLC-MS method for the simultaneous determination of nateglinide and its major metabolite M1.Methods Plasma samples were extracted with ethyl acetate and phenazocine was used as an internal standard.The chromatographic separation was performed on a Shimadzu C18 column(5μm,4.6 mm×250 mm)with a mobile phase of 0.1% formic acid solution and acetonitrile in gradient elution at a flow rate of 0.2 mL/min.The mass spectrometry was performed in selective ion monitoring(SIM)cation mode,and the detection objects[M+H]^(+)were:Nateglinide 318.2,M1334.1 and phenazocine 180.1.Results The linear ranges of the standard curves were 0.0625~8μg/mL for nateglinide and 0.0313~4μg/mL for M1.The intra-day and inter-day accuracy and precision variances were less than 10%,the plasma samples were stable,the extraction recoveries were all higher than 96%and the matrix effect was less than 5%.Conclusion The method is stable,sensitive and reproducible,and can be applied to the bioequivalence and pharmacokinetic study of nateglinide and its metabolite M1 in various biological samples.

关 键 词：那格列奈 代谢物M1 HPLC-MS法 药物代谢动力学 

分 类 号：R965[医药卫生—药理学]