Division of Pharmacy, Institute of Biomedical Research and Innovation Hospital, 2-2-1 Minatojima-minami-machi, Chuo-ku, Kobe 650-0047, Japan; Department of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
Department of Pharmaceutics, Faculty of Pharmaceutical Science, Kobe Gakuin University, 1-1-3 Minatojima, Chuo-ku, Kobe 650-8586, Japan.
J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Jun 15;1087-1088:1-5. doi: 10.1016/j.jchromb.2018.04.027. Epub 2018 Apr 13.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the quantification of gefitinib in dried blood spots (DBSs). Gefitinib was extracted with methanol from DBS of 3 mm in diameter and detected using a triple quadrupole mass spectrometer. The method was validated by evaluating its precision, accuracy, selectivity, carryover, matrix effect, recovery, and stability. For clinical validation, paired finger-prick DBS and plasma concentrations were compared for 10 patients with non-small cell lung cancer (NSCLC) taking gefitinib. The calibration linear range was 37.5-2400 ng/mL (coefficient of determination [R] = 0.99), encompassing the therapeutic concentrations of gefitinib. The accuracy and precision were within 15% of the quality control (QC) concentrations of 80, 200, and 2000 ng/mL. The lower limit of quantification was determined to be 40 ng/mL. Gefitinib was stable in DBSs for up to 5 months at room temperature and -20 °C, and at 40 °C for 24 h. A good correlation was observed between the gefitinib levels measured by the DBS method and plasma concentrations (R = 0.99). This method provides a simple, fast, and accurate approach to the quantitative analysis of gefitinib in finger-prick DBSs. The method would be useful for minimally invasive evaluation of the clinical gefitinib blood concentration.
建立并验证了一种用于测定干血斑（DBS）中吉非替尼浓度的液相色谱-串联质谱（LC-MS/MS）法。采用甲醇从 3mm 直径的 DBS 中提取吉非替尼，并用三重四极杆质谱仪进行检测。通过评估该方法的精密度、准确度、选择性、残留、基质效应、回收率和稳定性对其进行了验证。在临床验证中，对 10 名服用吉非替尼的非小细胞肺癌（NSCLC）患者进行了比较，对比了指尖 DBS 和血浆浓度。校准线性范围为 37.5-2400ng/mL（决定系数 [R] = 0.99），包含了吉非替尼的治疗浓度。准确度和精密度在 80、200 和 2000ng/mL 的质控（QC）浓度的 15%以内。定量下限确定为 40ng/mL。吉非替尼在 DBS 中室温下、-20°C 下和 40°C 下 24 小时内稳定。通过 DBS 法测量的吉非替尼水平与血浆浓度之间观察到良好的相关性（R = 0.99）。该方法提供了一种简单、快速、准确的方法，可用于指尖 DBS 中吉非替尼的定量分析。该方法将有助于对临床吉非替尼血药浓度进行微创评估。
