Mano Yuji
Drug Metabolism and Pharmacokinetics, Eisai Co., Ltd., Tokodai 5-1-3, Tsukuba-shi, Ibaraki 300-2635, Japan.
Pract Lab Med. 2018 May 24;12:e00103. doi: 10.1016/j.plabm.2018.e00103. eCollection 2018 Nov.
Cross validation studies for bioanalytical methods are important to ensure that assay data from all study sites where sample analysis is performed can be compared throughout clinical trials. To support global clinical studies of lenvatinib, a novel multi-targeted tyrosine kinase inhibitor, seven bioanalytical methods by liquid chromatography with tandem mass spectrometry (LC-MS/MS) were developed at five laboratories. In this study, methods were initially validated at each laboratory according to bioanalytical guidelines. For subsequent inter-laboratory cross validation, quality control (QC) samples and clinical study samples with blinded lenvatinib concentrations were assayed to confirm comparable assay data. Lenvatinib and an internal standard were extracted by protein precipitation, liquid-liquid extraction, or solid phase extraction and then detected in positive ion electrospray mode by multiple reaction monitoring using LC-MS/MS. The assay method developed at each laboratory was successfully validated with parameters within the acceptance criteria recommended by the guidelines. In the cross validation study, accuracy of QC samples was within± 15.3% and percentage bias for clinical study samples was within± 11.6%. These findings suggest that lenvatinib concentrations in human plasma can be compared across laboratories and clinical studies.
生物分析方法的交叉验证研究对于确保在所有进行样本分析的研究地点所获得的测定数据能够在整个临床试验中进行比较非常重要。为了支持新型多靶点酪氨酸激酶抑制剂乐伐替尼的全球临床研究，五个实验室开发了七种采用液相色谱-串联质谱法（LC-MS/MS）的生物分析方法。在本研究中，方法首先在每个实验室按照生物分析指南进行验证。对于后续的实验室间交叉验证，对质量控制（QC）样本和乐伐替尼浓度未知的临床研究样本进行检测，以确认测定数据具有可比性。乐伐替尼和内标通过蛋白沉淀、液液萃取或固相萃取进行提取，然后在正离子电喷雾模式下采用LC-MS/MS通过多反应监测进行检测。每个实验室开发的测定方法均成功通过验证，各项参数均在指南推荐的可接受标准范围内。在交叉验证研究中，QC样本的准确度在±15.3%以内，临床研究样本的偏差百分比在±11.6%以内。这些结果表明，不同实验室和临床研究中人体血浆中的乐伐替尼浓度具有可比性。
