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

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-10 mmol/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0.05～30.0 ng/mL和0.10～30.0 ng/mL范围内线性关系良好(r2＞0.99),定量限分别为0.05 ng/mL和0.10 ng/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.

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

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 multiple reaction monitoring.The assay was validated over the concentration ranges of 0.05-30.0 ng/mL for Ris 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.