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南京医科大学学报(自然科学版)                                  第42卷第9期
               ·1240 ·                    Journal of Nanjing Medical University(Natural Sciences)   2022年9月


             ·基础研究·

              LC⁃MS/MS 法同时测定大鼠血浆中来那度胺、伏立诺他和地塞

              米松的浓度



              张馨予 ,颜月园 ,刘 刚 ,胡玉涛              1
                                      1
                     1,2
                              1
               江苏联合职业技术学院连云港中医药分院,江苏                    连云港     222007;连云港市药物研发共性技术中心,江苏                 连云港
              1                                                       2
              222007


             [摘    要] 目的:建立了同时测定大鼠血浆中来那度胺、伏立诺他和地塞米松的液相色谱⁃质谱联用(liquid chromatography
              mass spectrometry,LC⁃MS)方法,并应用于大鼠药代动力学研究。方法:色谱柱为 Agilent Zorbax Eclipse Plus C 18柱(100 mm×
              2.1 mm,1.8 μm);流动相为5 mmol/L乙酸铵+0.1%甲酸水溶液⁃乙腈;采用梯度洗脱;体积流量0.6 mL/min;柱温35 ℃;进样量为
              5 μL;采用电喷雾离子源正离子模式(ESI ),多反应监测进行测定。结果:来那度胺、伏立诺他和地塞米松在各自的浓度范围
                                              +
              内检测值与浓度均具有良好的线性关系(R ≥0.995),三成分的日内和日间精密度的相对标准偏差(relative standard deviation,
                                               2
              RSD)值均小于 7.4%,准确度为 94.7%~106.7%,基质效应均在 92.3%~109.7%可接受范围内,平均提取回收率为 87.4%~
              103.6%,满足测定的要求。结论:经方法学验证,该方法可同时测定来那度胺、伏立诺他和地塞米松的血药浓度,快速、经济,
              为药物研究提供了重要的分析手段。
             [关键词] 来那度胺;伏立诺他;地塞米松;定量;超高效液相色谱质谱联用
             [中图分类号] R917                      [文献标志码] A                      [文章编号] 1007⁃4368(2022)09⁃1240⁃06
              doi:10.7655/NYDXBNS20220907


              Simultaneous determination of the lenalidomide,vorinostat and dexamethasone in rat

              plasma by LC⁃MS/MS
                          1,2
                                                   1
                                         1
              ZHANG Xinyu ,YAN Yueyuan ,LIU Gang ,HU Yutao   1
              1 Lianyungang TCM Branch of Jiangsu Union Technical Institute,Lianyungang 222007;Lianyungang Common
                                                                                           2
              Technological Center for Drug Research and Development,Lianyungang 222007,China
             [Abstract] Objective:A high performance liquid chromatography mass spectrometry (LC ⁃ MS) method was established to
              simultaneously quantify the lenalidomide,vorinostat and dexamethasone in rat plasma. The method was successfully applied to the
              plasma pharmacokinetics of lenalidomide,vorinostat and dexamethasone after oral administration to rats. Methods:The LC column was
              Agilent Zorbax Eclipse Plus C 18 (100 mm×2.1 mm,1.8 μm). The mobile phase was comprised of acetonitrile and water containing
              0.1% formic acid+5 mmol/L ammonium acetate. The gradient profile was used. Flow rate was 0.6 mL/min. Column temperature was
              35 ℃. Sample injection volume was 5 μL. The quantification was obtained by scanning with multiple reaction monitoring(MRM)via
              the positive electrospray ionization(ESI + ) source. Results:The correlation coefficients of the lenalidomide,vorinostat and
              dexamethasone,respectively were over 0.995. The relative standard deviation(RSD)values of the inter⁃ and intra⁃ precisions were less
              than 7.4%. The accuracy ranged from 94.7% to 106.7%. The matrix effect values were sufficiently minimized to 92.3%~109.7%. The
              average recoveries from rat plasma were 87.4% to 103.6%. Conclusion:The validated method is further applied to the determination of
              lenalidomide,vorinostat and dexamethasone in plasma. The method is rapid and economical,and can provide helpful information for
              pharmaceutical analysis.
             [Key words] lenalidomide;vorinostat;dexamethasone;quantification;LC⁃MS/MS
                                                                           [J Nanjing Med Univ,2022,42(09):1240⁃1245]
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