液相色谱-质谱-质谱联用技术同时测定犬血浆中头孢哌酮钠和他唑巴坦钠

Determination of the Content of Cefoperazone Sodium and Tazobactam Sodium in Dog Plasma by Liquid Chromatography-tandem Mass Spectrometry

目的:建立快速测定犬血浆中头孢哌酮钠和他唑巴坦钠含量的液相色谱-质谱-质谱(LC-MS-MS)联用方法。方法:血浆样品经甲醇沉淀蛋白后,以乙腈-水-甲酸(25:75:1.5)为流动相,流速0.2mL·min^(-1),采用 C_(18)柱分离,通过电喷雾化的四极杆串联质谱,以多离子反应监测(MRM)方式进行检测。用于定量分析的二级碎片离子分别为 m/z 530(头孢哌酮钠)和 m/z 168(他唑巴坦钠)。结果:头孢哌酮钠和他唑巴坦钠的线性范围分别为1～500μg·mL^(-1)和1～200μg·mL^(-1),每个样品测试时间为6 min。结论:该方法快速、准确,专属性强,操作简便,可用于犬血浆中头孢哌酮钠和他唑巴坦钠含量的测定及其临床药动学研究。

Objective：To develop a rapid and sensitive liquid -chromatography -tandem mass spectrometry （LC - MS- MS）method for determination of cefoperazone sodium and tazobactam sodium in dog plasma. Method：From 0. 4 mL plasma, cefoperazone and tazobactam were extracted with 0. 8 mL methanol, followed by liquid chromatography separation and mass spectrometric detection. The mobile phase consisted of acetronitrile -water -formic acid （25： 75： 1.5 ）, at a flow rate of 0. 2 mL · min^-1. Electrospray ionization （ESI） source was applied and operated in the positive ion mode. The multiple reaction monitoring（ MRM ）mode use the transitions of m/z 646→530 and m/z 301→168 were used to quantify the cefoperazone and the tazobactam, respectively. Results： The assay was linear from 1 to 500 μg · mL ^-1 （cefoperazone） and from 1 to 200 μg · mL^-1 （tazobactam）. The RSDs were less than 11% and 8% ,respectively. Conclusion：The method is shown to be suitable for clinical investigation of cefoperazone sodium tazobactam sodium pharmacokinetics, which offers advantages of specificity, speed and simpleness.