高效液相色谱-串联质谱法同时测定精神分裂症患者血浆中文拉法辛和阿立哌唑浓度

Simultaneous Determination of Venlafaxine and Aripiprazole in the Plasma of Patients with Schizophrenia by HPLC-MS/MS

目的建立同时测定人血浆中文拉法辛和阿立哌唑浓度的高效液相色谱-串联质谱(LC-MS/MS)法。方法色谱柱采用Phenomenex Kinetex XB-C18柱(50 mm×3 mm,2. 6μm),流动相为甲醇-2%甲酸水溶液(70∶30,等度洗脱),流速为0. 4 mL/min,柱温为40℃,进样量为5μL。使用电喷雾离子源(ESI),以多反应监测(MRM)模式进行正离子扫描,用于定量分析的离子对分别为m/z279. 3→58. 2(文拉法辛)、m/z 448. 3→285. 2(阿立哌唑)和m/z 279. 3→110. 2(内标)。结果文拉法辛与阿立哌唑的质量浓度分别在10~800 ng/mL和20~800 ng/m L范围内与峰面积线性关系良好,定量下限分别为10 ng/mL和20 ng/mL;日内、日间RSD均小于15%,提取回收率为(90. 24±5. 28)%^(110. 24±6. 74)%,基质效应为(91. 24±10. 75)%^(107. 32±11. 57)%。20例精神分裂症患者文拉法辛和阿立哌唑的血药浓度分别为140. 62~483. 54 ng/mL和140. 83~527. 65 ng/mL。结论该方法简单快速,专属性和灵敏度均良好,可用于精神分裂症患者体内文拉法辛和阿立哌唑血药浓度的测定。

Objective To establish a method for simultaneous determination of venlafaxine and aripiprazole in the plasma of patients with schizophrenia by HPLC-MS/MS.Methods The chromatographic column was Phenomenex Kinetex XB-C18(50 mm×3 mm,2.6μm),the mobile phase was methanol-2%formic acid in water(70∶30)by isocratic elution;the flow rate was 0.4 mL/min;the column temperature was 40℃;the injection volume was 5μL.Electrospray ionization source(ESI)was used,and positive ion scanning was conducted in multiple reaction monitoring(MRM)mode;the ion pairs used for quantitative analysis were m/z 279.3→58.2(venlafaxine),m/z 448.3→285.2(Aripiprazole)and m/z 279.3→110.2(internal standard).Results The linear relationship of venlafaxine and aripiprazole with the peak area were 10-800 and 20-800 ng/mL,respectively.The lower limits of quantification were 10 ng/mL and 20 ng/mL.The intra-day and intra-day RSDs were less than 15%;the extraction recoveries were(90.24±5.28)%-(110.24±6.74)%,and the matrix effect was(91.24±10.75)%-(107.32±11.57)%.The plasma concentrations of venlafaxine and aripiprazole in 20 schizophrenic patients were measured at 140.62-483.54 ng/mL and 140.83-527.65 ng/mL,respectively.Conclusion This method is simple,fast,and has good specificity and sensitivity.It is suitable for the determination of venlafaxine and aripiprazole in patients with schizophrenia.