Background: The trough concentration (C_min) of Imatinib (IM) is closely related to the treatment outcomes and adverse reactions of patients with gastrointestinal stromal tumors (GIST). However, the drug plasma level has great inter- and intra-individual variability, and therapeutic drug monitoring (TDM) is highly recommended.

Objective: To develop a novel, simple, and economical two-dimensional liquid chromatography method with the ultraviolet detector (2D-LC-UV) for simultaneous determination of IM and its major active metabolite, N-desmethyl imatinib (NDIM) in human plasma, and then apply the method for TDM of the drug.

Methods: The sample was processed by simple protein precipitation. Two target analytes were separated on the one-dimension column, captured on the middle column, and then transferred to the two-dimension column for further analysis. The detection was performed at 264 nm. The column temperature was maintained at 40˚C and the injection volume was 500 μL. Totally 32 plasma samples were obtained from patients with GIST who were receiving IM.

Results: IM and NDIM were separated well from other impurities and the entire analytical time for each run was 12.0 min. The calibration curves had good linearity in the range of 33.5-2678.4 ng/mL for IM, and 20.0-1600.0 ng/mL for NDIM, respectively. The extraction efficiency was more than 95%. The acceptable accuracy, precision, recovery and stability were also obtained. The C_min of the drug in patients was measured with the validated method.

Conclusion: The novel 2D-LC-UV method is simple, stable, highly automated and independent of specialized technicians, which greatly increases the real-time capability of routine TDM for IM in hospital.

背景：伊马替尼（IM）的谷浓度（C _min）与胃肠道间质瘤（GIST）患者的治疗结果和不良反应密切相关。然而，药物血浆水平具有很大的个体间和个体内变异性，强烈建议使用治疗药物监测 (TDM)。

目的：开发一种新型、简单、经济的二维液相色谱紫外检测器 (2D-LC-UV) 方法，用于同时测定人血浆中 IM 及其主要活性代谢物 N-去甲基伊马替尼 (NDIM)，然后应用该方法进行药物的TDM。

方法：样品通过简单的蛋白质沉淀处理。两种目标分析物在一维柱上分离，在中间柱上捕获，然后转移到二维柱上进行进一步分析。检测在 264 nm 处进行。柱温保持在 40°C，进样量为 500 μL。从接受 IM 的 GIST 患者中获得了总共 32 份血浆样本。

结果： IM 和 NDIM 与其他杂质分离良好，每次运行的整个分析时间为 12.0 分钟。IM 的校准曲线分别在 33.5-2678.4 ng/mL 和 NDIM 的 20.0-1600.0 ng/mL 范围内具有良好的线性。提取效率达95%以上。还获得了可接受的准确度、精密度、回收率和稳定性。使用经过验证的方法测量患者中药物的 C _min。

结论：新型二维-液相色谱-紫外方法简单、稳定、自动化程度高、独立于专业技术人员，大大提高了医院IM常规TDM的实时性。