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Simultaneous and Rapid Determination of Six Tyrosine Kinase Inhibitors in Patients with Non-Small Cell Lung Cancer Using HPLC-MS/MS
International Journal of Analytical Chemistry ( IF 1.8 ) Pub Date : 2021-09-17 , DOI: 10.1155/2021/5524361
Yanping Liu 1, 2 , Hua Liu 3 , Zhewei Xia 4 , Zhipeng Wang 1 , Yunlei Yun 1 , Guanying Zhang 2 , Lifeng Huang 2 , Shouhong Gao 1 , Wansheng Chen 1
Affiliation  

Objective. To develop a new method for quantitatively analyzing six tyrosine kinase inhibitors (gefitinib, erlotinib, icotinib, afatinib, osimertinib, and crizotinib) used in the treatment of non-small cell lung cancer (NSCLC) by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Methods. The analytes were detected in the selected reaction monitoring mode on a triple quadrupole mass spectrometer with the positive ionization mode. Carbamazepine was utilized as the internal standard. The pretreatment of the plasma sample was completed based on protein precipitation with acetonitrile, and the analytes were separated on an Agilent Zorbax SB-C18 reversed-phase column (2.1 mm × 100 mm, 3.5 μm, Agilent, USA) using gradient elution. The mobile phase consisted of 0.1% formic acid in water (phase A) and 0.1% formic acid in acetonitrile (phase B). The flow rate was 0.3 mL/min, and the injection volume was 5 μL. The column temperature was set and maintained at 35°C. Results. The calibration curves were linear over the range from 5.0 to 1000.0 ng/mL for gefitinib, crizotinib, and osimertinib; from 50.0 to 4000.0 ng/mL for icotinib and erlotinib; and from 5.0 to 400.0 ng/mL for afatinib. Linear correlation coefficients were >0.990 for all regression curves. The intra- and interday accuracy and precision of the method were within ±15.0% and not more than 15.0%, respectively. The mean recovery of all the analytes ranged from 70.18% to 110.76%, the matrix effect was from 88.85% to 127.58%, and stability was within ±15.0%. Conclusion. This newly developed method was sensitive, simple, and robust and could be used in therapeutic drug monitoring of six tyrosine kinase inhibitors in NSCLC patients.

中文翻译:

使用 HPLC-MS/MS 同时快速测定非小细胞肺癌患者的六种酪氨酸激酶抑制剂

客观。开发一种通过液相色谱-串联质谱(LC-质谱/质谱)。方法。在采用正离子模式的三重四极杆质谱仪上以选定的反应监测模式检测分析物。卡马西平用作内标。血浆样品的预处理基于用乙腈沉淀蛋白质完成,分析物在 Agilent Zorbax SB-C18 反相柱 (2.1 mm × 100 mm, 3.5  μm,安捷伦,美国)使用梯度洗脱。流动相由 0.1% 甲酸水溶液(A 相)和 0.1% 甲酸乙腈溶液(B 相)组成。流速为 0.3 mL/min,进样量为 5  μL。柱温设定并保持在 35°C。结果. 吉非替尼、克唑替尼和奥希替尼的校准曲线在 5.0 至 1000.0 ng/mL 范围内呈线性;埃克替尼和厄洛替尼从 50.0 到 4000.0 ng/mL;阿法替尼从 5.0 到 400.0 ng/mL。所有回归曲线的线性相关系数 > 0.990。该方法的日内和日间准确度和精密度分别在±15.0%以内和不超过15.0%。所有分析物的平均回收率为70.18%~110.76%,基质效应为88.85%~127.58%,稳定性在±15.0%以内。结论。这种新开发的方法灵敏、简单、稳健,可用于 NSCLC 患者中六种酪氨酸激酶抑制剂的治疗药物监测。
更新日期:2021-09-20
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