A simple, efficient, and stable detection method of two-dimensional liquid chromatography (2D-LC) was established and validated to determine anlotinib in the human plasma. The 2D-LC system comprises a first-dimensional column (LC1), an intermediate transfer column, and a second-dimensional column (LC2). With simple protein precipitation treatment, the samples were processed directly for detection. The analysis cycle time was completed within 9.50 min. For the anlotinib concentrations, the calibration curve was linear over the 5.00–320.00 ng/mL range. The intra-day and inter-day precision ranges were 0.77–6.22% and 1.92–4.26%, respectively, for anlotinib concentrations. The recoveries were in the range of 97.85–102.50%. A total of 135 plasma samples from 94 patients were analyzed by our method. The plasma concentrations of patients were in the range of 5.17–106.38 ng/mL, in which the female had a higher plasma concentration (6.44–106.38 ng/mL). The simultaneous application of dexamethasone can increase the anlotinib concentration in the plasma. In our clinical application, we found that the factors that affect the plasma concentration include the time and dose of the medication, gender, and drug interactions. The method appears to be sensitive, precise, selective, and suitable for determining the concentration of anlotinib in the plasma sample.

中文翻译：

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一种使用二维液相色谱法定量人血浆中安罗替尼的新方法

建立并验证了一种简单、高效、稳定的二维液相色谱（2D-LC）检测方法，用于测定人血浆中的安罗替尼。2D-LC 系统包括一维柱 (LC1)、中间转移柱和二维柱 (LC2)。采用简单的蛋白质沉淀处理，直接处理样品进行检测。分析周期时间在 9.50 分钟内完成。对于安罗替尼浓度，校准曲线在 5.00–320.00 ng/mL 范围内呈线性。安罗替尼浓度的日内和日间精度范围分别为 0.77-6.22% 和 1.92-4.26%。回收率在 97.85-102.50% 的范围内。通过我们的方法分析了来自 94 名患者的 135 份血浆样本。患者血浆浓度范围为5.17~106.38 ng/mL，其中女性血浆浓度较高（6.44~106.38 ng/mL）。同时应用地塞米松可增加血浆中安罗替尼浓度。在我们的临床应用中，我们发现影响血药浓度的因素包括用药的时间和剂量、性别和药物相互作用。该方法似乎灵敏、精确、选择性好，适用于测定血浆样品中安罗替尼的浓度。我们发现影响血浆浓度的因素包括服药的时间和剂量、性别和药物相互作用。该方法似乎灵敏、精确、选择性好，适用于测定血浆样品中安罗替尼的浓度。我们发现影响血浆浓度的因素包括服药的时间和剂量、性别和药物相互作用。该方法似乎灵敏、精确、选择性好，适用于测定血浆样品中安罗替尼的浓度。