用于测定大鼠血浆中奥曲奈（TAK-700）的高灵敏度液相色谱-电喷雾串联质谱法的建立与验证：在药代动力学研究中的应用
Development and validation of a highly sensitive LC-ESI-MS/MS method for the determination of Orteronel® (TAK-700) in rat plasma: application to a pharmacokinetic study.
作者信息
Gurav Sandip, Police Anitha, Zainuddin Mohd, Farooqui Junaid Hassan, Reddy G Krishna, Kethiri Raghava Reddy, Rajagopal Sriram, Mullangi Ramesh
机构信息
Drug Metabolism & Pharmacokinetics, Jubilant Biosys Ltd, Industrial Suburb, Yeshwanthpur, Bangalore-560 022, India.
出版信息
Bioanalysis. 2012 Jun;4(12):1471-80. doi: 10.4155/bio.12.107.
BACKGROUND
A highly sensitive, specific and high-throughput LC-ESI-MS/MS method in the positive mode has been developed and validated for the quantitation of Orteronel® (TAK-700) in rat plasma using YM-55208 as an internal standard.
RESULTS
The assay procedure involves extraction of Orteronel and internal standard from rat plasma with liquid-liquid extraction method. Chromatographic separation was achieved using an isocratic mobile phase at a flow rate of 0.6 ml/min on an Atlantis dC18 column with a total run time of 2.5 min. The MS/MS ion transitions monitored were m/z 308.4→95.0 for Orteronel and m/z 262.3→194.2 for IS. Method validation was performed as per US FDA guidelines. The LLOQ achieved was 0.42 ng/ml and the linearity range extended from 0.42 to 814 ng/ml.
CONCLUSION
The results met the acceptance criteria. The validated method was successfully applied to characterize the pharmacokinetic parameters of Orteronel in rat plasma.
背景
已开发并验证了一种高灵敏度、高特异性且高通量的正模式液相色谱 - 电喷雾串联质谱（LC - ESI - MS/MS）方法，用于以YM - 55208作为内标定量大鼠血浆中的奥特仑（TAK - 700）。
结果
该分析方法采用液 - 液萃取法从大鼠血浆中提取奥特仑和内标。在Atlantis dC18柱上，以0.6 ml/min的流速使用等度流动相进行色谱分离，总运行时间为2.5分钟。监测的MS/MS离子跃迁对于奥特仑为m/z 308.4→95.0，对于内标为m/z 262.3→l94.2。按照美国食品药品监督管理局（US FDA）指南进行方法验证。最低定量限（LLOQ）为0.42 ng/ml，线性范围从0.42扩展至814 ng/ml。
结论
结果符合验收标准。经验证的方法成功应用于表征大鼠血浆中奥特仑的药代动力学参数。
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