超高效液相色谱-串联质谱法测定犬血浆中利培酮和帕潘立酮及药代动力学研究

Determination of Risperidone and Paliperidone in Beagle Plasma by UPLC-MS/MS and Their Pharmacokinetics Studies

建立了超高效液相色谱-串联质谱法(UPLC-MS/MS)测定犬血浆中利培酮和帕潘立酮的浓度。血浆样品用乙腈沉淀蛋白后,用Zorbax SB-C18柱分离,以乙腈-10mmol/L乙酸铵溶液(65∶35,V/V)为流动相,在电喷雾离子源正离子模式下以多反应监测(MRM)方式进行检测。利培酮、帕潘立酮分别在0.05~30.0ng/mL和0.10~30.0ng/mL范围内线性关系良好(r^2>0.99),定量限分别为0.05ng/mL和0.10ng/mL,回收率分别为91.2%~95.1%和93.1%~97.5%。该方法精密、准确、快速,适用于临床血药浓度的监测及利培酮缓释微球药动学的研究。

A method was developed for the determination of risperidone （Ris） and paliperidone （Pal） in beagle plasma by ultra performance liquid chromatography-tandem mass spectrometry. One-step protein precipitation with acetonitrile was used to extract the analytes from the plasma, and then separated on a Zorbax SB C18 column using a mixture of acetonitrile-10 mmol/L ammonium acetate（65：35 ,V/V） as the mobile phase. Detection was performed on electrospray positive ionization mass spectrometry by muhip reaction monitoring. The assay was validated over the concentration ranges of 0.05-30.0 ng/mL for R e and 0.10-30.0 ng/mL for Pal with limits of quantitation of 0.05 ng/mL and 0.10 ng/mL,and the recoveries were 91. 2%-95. 1% and 93. 1%-97. 5%, respectively. The method, which offers advantages of specificity, speed, and sensitivity is proved to be suitable for clinical investigation of risperridon microsphere pharmacokinetics.