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目的建立LC-MS/MS法测定比格犬血浆中米非司酮的浓度。方法血浆样品以特非那定为内标,采用高效液相色谱分离系统,色谱柱为Kinetex-C18 110 A柱(3 mm×30 mm,2.6μm),流动相为甲醇-水(0.1%甲酸),流速为0.8ml/min;采用质谱检测系统,电喷雾电离,正离子检测,定量采集方式为多反应监测模式(MRM),米非司酮m/z 430.2→372.3,内标特非那定m/z 472.2→436.2;离子喷雾电压5 500V。对改良方法的专属性、标准曲线最低定量下限(LLOQ)、精密度与准确度、稳定性、基质效应和提取回收率等进行性能验证。结果米非司酮在11 000ng/ml浓度范围内线性关系良好,LLOQ为1ng/ml,信噪比(S/N)>10;日内精密度≤11.6%,日间精密度≤9.9%,日内准确度≤11.1%,日间准确度≤7.8%;回收率为91.5%~104.0%。结论该检测方法简单、快速、灵敏、准确,适用于米非司酮在比格犬中血药浓度检测及其药物代谢动力性研究。
Abstract：Objective:To establish a LC-MS/MS method for quantitative determination of mifepristone in the plasma of Beagle dog.Methods: Plasma samples were prepared and separated by a Kinetex-C18 110 Acolumn(3 mm×30 mm,2.6μm)in a flow phase consisting of methanol and water(0.1% formic acid)at a flow rate of0.8 ml/min,with terfenadine as the internal standard(IS).The ESI electrospray ionization and positive ion detection in Mass spectrometry system were used.Quantitative collection was used with the multiple reaction monitoring(MRM)mode:m/z 430.2→m/z 372.3 for mifepristone and m/z 472.2→m/z 436.2 for standard(IS).Ionspray voltage:5 500 V.The specificity,standard curve,the lower limit of quantization(LLOQ),precisions and accuracies,stability,matrix effect and recovery rate of the LC-MS/MS were evaluated.Results:Mifepristone had a good linear relationship in the range of 1-1 000 ng/ml.The lowest quantitative limit was 1 ng/ml,the signal-to-noise ratio S/N>10,the intra-day precision≤11.6%,the inter-day precision≤9.9%,the intra-day accuracy less than 11.1%,the inter-day accuracy less than 7.8%,and the extraction recovery was 91.5%-104.0%Conclusions:The quantitative determination of mifepristone is a simple,rapid,sensitive and accurate method.It can be used to detect the concentration of mifepristone in the blood of Beagle dogs and to study the pharmacokinetics of mifepristone.
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基本信息:
中图分类号:R965
引用信息:
[1]郭永,贾重阳,许保海,等.LC-MS/MS法测定比格犬血浆中米非司酮的方法学建立[J].生殖医学杂志,2018,27(10):1011-1019.
基金信息:
2016年国家重点研发计划(2016YFC1000905);; 中央级公益性科研院所基本科研业务费专项(2017GJZ04)
2018-10-15
2018-10-15