付瑶,徐海燕,吴瑞阳,袁波
FU Yao,XU Hai-yan,WU Rui-yang,YUAN Bo(School of Pharmacy

• 1:沈阳药科大学药学院

摘要(Abstract)：

目的建立Beagle犬血浆中美托拉宗浓度的液相色谱-串联质谱(LC-MS/MS)测定方法。方法色谱柱:依利特C18柱(150 mm×4.6 mm,5μm),流动相:乙腈-5 mmol.L-1醋酸铵-甲酸(体积比为60.00:40.00:0.05),血浆样品采用乙腈沉淀蛋白法处理,以多反应监测(multiple reaction moni-toring,MRM)扫描方式检测,测定Beagle犬口服美托拉宗后血浆中药物浓度。结果血浆中美托拉宗质量浓度在0.5～200.0μg.L-1内线性关系良好,r=0.995 2;日内和日间精密度RSD≤12.2%;美托拉宗的平均提取回收率为66.0%～72.9%,基质效应符合有关规定,美托拉宗在Beagle犬血浆中主要药物动力学参数:t1/2为(7.6±2.1)h,ρmax为(144.2±29.5)μg.L-1,AUC0-∞为(2081.5±516.0)μg.h.L-1。结论该方法适用于美托拉宗在Beagle犬体内的药物动力学研究。
Objective To develop a simple,rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for the determination of metolazone in dog plasma.Methods Protein precipitation was used for the sample pretreatment with a plasma volume of 100 μL.The chromatographic separation was carried out on an Elite C18 analytical column(150 mm×4.6 mm,5 μm)at a flow rate of 0.5 mL min-1 and the mobile phase was composed of acetonitrile-5 mmol · L-1 ammonium acetate-formic acid(V∶ V∶ V=60.00∶ 40.00∶ 0.05).Detection was carried out by multiple reaction monitoring.Results The method was linear over the range of 0.5-200.0 μg · L-1 and the lower limit of quantification(LLOQ)was 0.5 μg · L-1.The intra-and inter-day precision was within 12.2% in terms of relative standard deviation(RSD%).The average recoveries were between 66.0%-72.9%,the matrix effects were between 55.6-62.1%.Main pharmacokinetic parameters were as follows:t1/2(7.6±2.1)h,ρmax(144.2±29.5)μg · L-1,AUC0-∞(2 081.5±516.0)μg · h · L-1,respectively.Conclusions This simple and sensitive LC-MS/MS method was successfully applied to pharmacokinetic studies of metolazone in Beagle dogs after an oral dose of 5.0 mg metolazone.

关键词(KeyWords)： 美托拉宗;LC-MS/MS;Beagle犬;药物动力学
metolazone;liquid chromatography-tandem mass spectrometry(LC-MS/MS);Beagle dog;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 付瑶,徐海燕,吴瑞阳,袁波
FU Yao,XU Hai-yan,WU Rui-yang,YUAN Bo(School of Pharmacy

DOI: 10.14066/j.cnki.cn21-1349/r.2012.12.015

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