高效液相色谱法常规监测中国胃肠间质瘤患者体内的伊马替尼血药浓度

doi:10.5246/jcps.2020.09.059

摘要/Abstract

摘要：

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InertSustain C₁₈柱(250 mm×4.6 mm, 5 µM)进行分离, 流动相为25 mM NH₄H₂PO₄ (pH = 8)–乙腈(61:39, v/v), 柱温为40 ºC, 流速为1 mL/min, 紫外检测波长为265 nm。该方法标准曲线在50–10 000 ng/mL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。

关键词: 伊马替尼, 高效液相色谱, 胃肠间质瘤, 治疗药物监测, 样品再分析

Abstract:

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 g K₂CO₃ and 0.65 g KCl dissolved in 5 mL ultrapure water). The chromatographic separation was performed on an InertSustain C₁₈ column (250 mm×4.6 mm, 5 µM) maintained at 40 ºC utilizing the mobile phase consisted of 25 mM NH₄H₂PO₄ (pH 8.0)–acetonitrile (61:39, v/v) at a flow rate of 1 mL/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/mL. 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%.

Key words: Imatinib, HPLC, Gastrointestinal stromal tumor, Therapeutic drug monitoring, Incurred sample reanalysis

中图分类号:

R917

Supporting:

周毅, 赖俊莉, 邱峰, 张军. 高效液相色谱法常规监测中国胃肠间质瘤患者体内的伊马替尼血药浓度[J]. 中国药学(英文版), 2020, 29(9): 637-648.

Yi Zhou, Junli Lai, Feng Qiu, Jun Zhang. Development and validation of an HPLC-UV method for routine trough plasma concentration monitoring of imatinib in Chinese patients with gastrointestinal stromal tumor[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(9): 637-648.

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