摘要
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1~1 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。
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 A column（3 mm 30 mm,2.6 μm） in a flow phase consisting of methanol and water （0.1% formic acid）at a flow rate of 0.8 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 method. It can be used to detect the concentration of pharmacokinetics is a simple, rapid, sensitive and accurate in the blood of Beagle dogs and to studythe pharmacokinetics of mifepristone.
作者
郭永
贾重阳
许保海
涂鹏程
裴开颜
GUO Yong;JIA Chong-Nang;XU Bao-hal;TU Peng-cheng;PEI Kai-yan(National Research Institute for Family Planning,Beijing 100081;The No.2 People＇s Hospital of Lanzhou,Lanzhou 730046;Department of Cell Biology,Zunyi Medical University,Zunyi 563003;Peking Union Medical College,Beijing 100730)
出处
《生殖医学杂志》
CAS
2018年第10期1011-1019,共9页
Journal of Reproductive Medicine
基金
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)
