基于胶束液相色谱法定量酪氨酸激酶抑制剂阿西替尼的方法,据报道血浆中的拉帕替尼和阿法替尼。样品预处理是在纯胶束溶液中简单的1/5稀释,过滤和直接注射,无需提取或纯化步骤。三种药物在17min内从基质中分离,使用0.07M十二烷基硫酸钠-6.0%1-戊醇的水溶液,在pH7下用0.01M磷酸盐作为流动相缓冲,在等度模式下以1mL/min通过C18柱运行。通过在260nm处的吸光度进行检测。在每种药物的保留因子与流动相中表面活性剂/有机溶剂浓度之间建立了准确的数学关系,通过有限数量的实验实现,为了优化这些因素。发现了分析物与胶束的结合行为。该方法在以下方面得到了欧洲药品管理局指南的成功验证:选择性,线性度(r2>0.9995),校准范围(0.5至10mg/L),检测限(0.2mg/L),结转效应,准确度(-8.1至+6.9%),精度(<13.8%),稀释完整性,基体效应,稳定性和鲁棒性。该程序被认为是可靠的,实用,经济,可访问,短时间,易于处理,便宜,环境友好,安全,可用于每天分析许多样品。最后,将该方法应用于费用分析,在同一分析运行中使用质量控制样品,有足够的结果。因此,它可用于临床实验室的常规分析。
A method based on micellar liquid chromatography to quantify the tyrosine kinase inhibitors
axitinib, lapatinib and afatinib in plasma is reported. The sample pretreatment was a simple 1/5-dilution in a pure micellar solution, filtration and direct injection, without requiring extraction or purification steps. The three drugs were resolved from the matrix in 17min, using an aqueous solution of 0.07M sodium dodecyl sulfate - 6.0% 1-pentanol, buffered at pH7 with 0.01M phosphate salt as mobile phase, running under isocratic mode at 1mL/min through a C18 column. The detection was performed by absorbance at 260nm. An accurate mathematical relationship was established between the retention factor of each drug and the surfactant/organic solvent concentration in the mobile phase, achieved with a limited number of experiments, in order to optimize these factors. A binding behavior of the analytes face to the micelles was found out. The method was successfully validated by the
guidelines of the European Medicines Agency in terms of: selectivity, linearity (r2>0.9995), calibration range (0.5 to 10mg/L), limit of detection (0.2mg/L), carry-over effect, accuracy (-8.1 to +6.9%), precision (<13.8%), dilution integrity, matrix effect, stability and robustness. The procedure was found reliable, practical, economic, accessible, short-time, easy-to-handle, inexpensive, environmental-friendly, safe, useful for the analysis of many samples per day. Finally, the method was applied to the analysis of incurred, using quality control samples in the same analytical run, with adequate results. Therefore, it can be implementable for routine analysis in clinical laboratories.