摘要
Imatinib is the first-line medication for the treatment of advanced gastrointestinal stromal tumor(GIST). Due to the large inter-individual variability, it is recommended to monitor the trough plasma concentration of imatinib to ensure the efficacy and safety of imatinib therapy. In the present study, an HPLC-UV method was developed and validated for quantitating imatinib in the plasma of Chinese GIST patients. The samples were processed by protein precipitation and then mixed with a neutralizing agent(1.4 gK2CO3 and 0.65g KCl dissolved in 5mL ultrapure water). The chromatographic separation was performed on an Inert Sustain C18 column(250 mm×4.6 mm, 5 μM) maintained at 40 ℃ utilizing the mobile phase consisted of 25 m MNH4H2PO4(pH 8.0)–acetonitrile(61:39, v/v) at a flow rate of 1 m L/min, with an ultraviolet detector set at 265 nm. The method was fully validated according to the published guidelines. The plotted calibration curves were all linear within the range of 50 to 10 000 ng/m L. The validation results of the intra-day and inter-day accuracies and precisions ranged from –5.81% to 6.33%. The extraction recoveries were within the range of 92.38% to 97.86%. All the results of stability studies were all consistent with the acceptance criteria of within ±15%. Finally, the method was successfully applied to trough plasma concentration monitoring of imatinib in 150 Chinese GIST patients orally administrated with imatinib. Incurred sample reanalysis was conducted, results of which were also in accordance with the acceptance criteria of within ±20%.
伊马替尼目前是胃肠间质瘤的一线治疗用药。由于伊马替尼在不同患者体内血药浓度差异较大,目前指南推荐常规监测伊马替尼的血药浓度以提高伊马替尼的疗效,降低不良反应的发生率。本研究建立了一种简单灵敏快速的高效液相色谱法,采用简单的沉淀蛋白法处理血浆样品,处理后的样品通过色谱柱Inert Sustain C18柱(250mm×4.6 mm, 5μM)进行分离,流动相为25 mM NH4H2PO4 (pH=8)–乙腈(61:39, v/v),柱温为40℃,流速为1mL/min,紫外检测波长为265nm。该方法标准曲线在50–10 000 ng/m L浓度范围内线性良好,日间与日内准确度和精密度在–5.81%–6.33%之间。绝对回收率在92.38%–97.86%之间。稳定性测试和样品再分析结果均符合指南要求。该方法成功用于150名中国胃肠间质瘤患者的常规伊马替尼血药浓度监测。
