表皮生长因子受体酪氨酸激酶抑制剂(EGFR-TKIs),如埃克替尼,奥希替尼,对于EGFR突变的非小细胞肺癌(NSCLC)患者而言,aumroletinib和aumertinib已成为有希望的治疗选择.此外,安洛替尼,靶向VEGFR的抗血管生成剂,FGFR,和PDGFR,已在NSCLC病例中与EGFR-TKIs联合使用。建立并验证了超高效液相色谱-串联质谱(UPLC-MS/MS)定量埃克替尼的方法,奥希替尼,aumolertinib和anlotinib同时用于临床TDM。使用KinetexC18柱(100mm×2.1mm)和在用0.1%甲酸酸化的水中和在乙腈中的乙酸铵的洗脱梯度进行色谱分离。该测定在4-2000ng/mL的线性范围内进行了验证,奥希替尼2-1000ng/mL,aumolertinib为1-500ng/mL,和0.8-400纳克/毫升的安洛替尼,遵循FDA关于生物分析方法的指南。定量方法在选择性方面表现出令人满意的性能,准确度(从91.3%到107%),精度(日内和日间变化系数范围为0.944%至7.48%),线性度回收率(从86.0%到91.9%),基体效应(IS归一化矩阵因子为96.7%至102%),和稳定性。总的来说,该方法被证明是敏感的,可靠,而且直截了当,能够成功同时测定埃克替尼的血药浓度,奥希替尼,aumolertinib,和患者的安洛替尼。该方法的有效性已在各种仪器中得到证实。
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as icotinib,
osimertinib, and aumolertinib have emerged as promising treatment options for EGFR mutated Non-small cell lung cancer (NSCLC) patients. Additionally, anlotinib, an anti-angiogenic agent targeting VEGFR, FGFR, and PDGFR, has been used in combination with EGFR-TKIs in NSCLC cases. A method utilizing ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was developed and validated for quantifying icotinib,
osimertinib, aumolertinib and anlotinib simultaneously in clinical TDM. The chromatographic separation was performed using a Kinetex C18 column (100 mm × 2.1 mm) and an elution gradient of ammonium acetate in water acidified with 0.1 % formic acid and in acetonitrile. The assay was validated over a linear range of 4-2000 ng/mL for icotinib, 2-1000 ng/mL for
osimertinib, 1-500 ng/mL for aumolertinib, and 0.8-400 ng/mL for anlotinib, following the guidelines on bioanalytical methods by FDA. The quantification method exhibited satisfactory performance in terms of selectivity, accuracy (from 91.3 % to 107 %), precision (intra- and inter-day coeffficients of variation ranged from 0.944 % to 7.48 %), linearity, recovery (from 86.0 % to 91.9 %), matrix effect (IS-normalized matrix factors were from 96.7 % to 102 %), and stability. Overall, the method proved to be sensitive, reliable, and straightforward, enabling successful simultaneous determination of blood concentrations of icotinib,
osimertinib, aumolertinib, and anlotinib in patients. The validity of the method has been confirmed across various instruments.