Application of a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to the pharmacokinetics of ON01910 in brain tumor-bearing mice.
Application of a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to the pharmacokinetics of ON01910 in brain tumor-bearing mice.
复制标题
应用液相色谱-串联质谱 (LC/MS/MS) 方法研究 ON01910 在脑肿瘤小鼠体内的药代动力学。
DOI：
10.1016/j.jpba.2011.08.003
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发表时间：
2011
影响因子：
3.4
通讯作者：
Gallo,JamesM
中科院分区：
文献类型：
--
作者：
Nuthalapati,Silpa;Guo,Ping;Zhou,Qingyu;Reddy,MVRamana;Reddy,EPremkumar;Gallo,JamesM
ON 01910是一种小分子量苄基苯乙烯砜，目前正在研究作为一种新型抗癌剂。本研究的目的是开发一种灵敏且可重现的液相色谱-串联质谱（LC/MS/MS）方法，以定量测定少量五种生物基质（小鼠血浆、粪便、尿液、正常脑和脑肿瘤）中的ON 01910水平。对于所有基质，使用蛋白沉淀样品制备液，得到线性校准曲线，决定系数大于0.99。除小鼠尿液为10 ng/ml外，所有基质的定量下限（LLOQ）均为5 ng/ml。所有基质的校准标准曲线均具有重现性，除小鼠血浆中LLOQ的准确度在17%范围内外，所有质控浓度下精密度和准确度的日间和日内变异性均小于15%。该测定法成功地应用于表征ON 01910的全身药代动力学以及其在小鼠脑和脑肿瘤中的处置。静脉注射50 mg/kg剂量时，ON 01910的清除率为3.61± 0.85 l/h/kg，半衰期为8.66± 3.30 h。
ON01910 is a small molecular weight benzyl styryl sulfone currently under investigation as a novel anticancer agent. The purpose of the investigation was to develop a sensitive and reproducible liquid chromatography–tandem mass spectrometry (LC/MS/MS) method to quantitate levels of ON01910 in small amounts of five biological matrices; mouse plasma, feces, urine, normal brain and brain tumor. For all matrices, protein precipitation sample preparation was used that led to linear calibration curves with coefficients of determination greater than 0.99. The lower limit of quantitation (LLOQ) for all matrices was 5ng/ml except that for mouse urine which was 10ng/ml. The calibration standard curves were reproducible for all matrices with inter- and intra-day variability in precision and accuracy being less than 15% at all quality control concentrations except for the LLOQ in mouse plasma for which the accuracy was within 17%. The assay was successfully applied to characterize the systemic pharmacokinetics of ON01910 as well as its disposition in brain and brain tumor in mice. ON01910 exhibited a clearance of 3.61±0.85l/h/kg and a half life of 8.66±3.30h at 50mg/kg dose given I.V.