UPLC-MS/MS法研究来那度胺在小鼠体内的组织分布

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英文篇名：Study of the distribution of lenalidomide in mice by UPLC-MS/MS 作者：罗莉娅 ; 邓星 ; 苟立平 ; 汤明海 ; 万丽 英文作者：LUO Li-ya;DENG Xing;GOU Li-ping;TANG Ming-hai;WAN Li;School of Pharmacy, Chengdu University of Traditional Chinese Medicine;Cancer Biotherapy Laboratorym West China Hospitalm Sichuan University; 关键词：来那度胺 ; UPLC-MS/MS ; 组织分布 ; 小鼠 英文关键词：lenalidomide;;UPLC-MS/MS;;tissue distribution;;mouse 中文刊名：GLYZ 英文刊名：The Chinese Journal of Clinical Pharmacology 机构：成都中医药大学药学院;四川大学华西医院肿瘤生物治疗研究室; 出版日期：2019-07-28 出版单位：中国临床药理学杂志 年：2019 期：v.35;No.292 基金：国家自然科学基金资助项目(81673653) 语种：中文; 页：GLYZ201914025 页数：5 CN：14 ISSN：11-2220/R 分类号：91-95

摘要

目的建立超高效液相色谱串联质谱(UPLC-MS/MS)法快速测定小鼠血浆和组织中来那度胺的浓度,并研究其在小鼠体内的组织分布。方法C57BL/6J小鼠腹腔给药后采集不同时间点的血浆及组织进行药代动力学分析。样品选用蛋白沉淀法处理,色谱柱为Waters Acquity UPLC BEH C_(18)(1. 7μm,2. 1mm×50 mm),流动相为乙腈-0. 3%甲酸水(40∶60),0. 5 mL·min~(-1)等度洗脱。用电喷雾电离源(ESI)正离子模式、多反应监测(MRM),选择来那度胺m/z260. 0→m/z 149. 1和内标(D3-PM) m/z 494. 2→m/z 326. 1作为监测离子对进行检测。结果来那度胺在0. 98～1000 ng·mL~(-1)线性关系良好,血浆标准曲线方程为y=9. 18×10~(-4)x-4. 64×10~(-4)(r=0. 997 5),基质效应、回收率、精密度、稀释效应、稳定性的RSD均小于15%。给药后,来那度胺在小鼠的肾、血、脾、小肠、肝等组织分布较多,其他组织中的浓度较小,尤其在脑中分布极少。结论该方法简便、准确、灵敏度高,分析时间短,可用于来那度胺在血浆及组织样品中的检测及药代动力学研究。
        Objective To establish a sensitive and rapid ultra-high performance liquid chromatographic-tandem mass spectrometric( UPLC-MS/MS) method for determination of lenalidomide in mouse plasma and tissues,and to study the tissue distribution in mice. Methods The plasma and tissues of C57BL/6J mice were collected for intraperitoneal administration at different time points for pharmacokinetic analysis. The sample is treated with protein precipitation,the analytes were separated on Waters Acquity UPLC BEH C_(18)( 1. 7 μm,2. 1 mm × 50 mm)column. The mobile phase was acetonitrile-0. 3% formic acid water( 40:60),eluted isocratically at 0. 5 mL·min~(-1). An AB QTRAP 5500 tandem mass spectrometer equipped with an electrospray ionization source and operated in positive ion mode was used as detector. The mass transition ion-pairs were m/z 260. 0 → m/z 149. 1( lenalidomide) and m/z 494. 2→m/z 326. 1( ISD3-PM). Results This study examined the methodology in plasma. The linear calibration curves for lenalidomide showed a good linear relationship. The standard curve equation of lenalidomide in mouse plasma was y = 9. 18 × 10~(-4) x-4. 64 × 10~(-4)( 0. 98-1000 ng·mL~(-1),r =0. 997 5). The RSD of matrix effect,recovery,precision,dilution effect and stability were all less than 15%. Lenalidomide is distributed more in the kidney,blood,spleen,small intestine,liver and other tissues. The concentration of lenalidomide in other tissues is small,especially in the brain after being given the drug. Conclusion The established UPLC-MS/MS method is simple,accurate,sensitive and rapid,It can be used for the detection and pharmacokinetic study of lenalidomide.

引文

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