Utrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht, The Netherlands.
J Chromatogr B Analyt Technol Biomed Life Sci. 2012 Sep 15;905:137-40. doi: 10.1016/j.jchromb.2012.08.004. Epub 2012 Aug 10.
A quantitative bioanalytical liquid chromatography-tandem mass spectrometric assay for the tyrosine kinase inhibitor pazopanib was developed and validated. Plasma samples were pre-treated using protein precipitation with acetonitrile containing pazopanib-d(4) as internal standard. The extract was injected into the chromatographic system after dilution with water (1:9, v/v). The system consisted of a sub-2 μm particle, trifunctional bonded octadecyl silica column with isocratic elution using 0.005% (v/v) of formic acid in a mixture of water (76%, v/v) and acetonitrile (24%, v/v). The analyte was quantified using the selected reaction monitoring mode of a triple quadrupole mass spectrometer with a heated electrospray interface. The assay was validated in a 0.1-100 μg/ml calibration range. Within day precisions were 3.6-5.2%, between day precisions 4.0-8.3% and accuracies between 106% and 113% for the whole calibration range. The drug was sufficiently stable under all relevant analytical conditions. The assay has successfully been used to assess drug levels for therapeutic drug monitoring in patients treated with pazopanib.
建立并验证了一种用于检测酪氨酸激酶抑制剂帕唑帕尼的定量生物分析液相色谱-串联质谱法。采用含帕唑帕尼-d4（内标）的乙腈进行蛋白沉淀预处理血浆样品。将提取物用 1:9（v/v）的水稀释后注入色谱系统。该系统由亚 2μm 粒径、三官能键合十八烷基硅胶柱组成，采用水（76%，v/v）和乙腈（24%，v/v）混合物中的 0.005%（v/v）甲酸进行等度洗脱。采用加热电喷雾接口的三重四极杆质谱仪的选择反应监测模式对分析物进行定量。在 0.1-100μg/ml 的校准范围内进行了方法验证。整个校准范围内，日内精密度为 3.6-5.2%，日间精密度为 4.0-8.3%，准确度为 106%-113%。在所有相关分析条件下，该药物均稳定。该方法已成功用于评估接受帕唑帕尼治疗的患者的治疗药物监测中的药物水平。
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