Cancer Science Institute of Singapore, National University of Singapore, Singapore.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Jul 15;879(22):2155-61. doi: 10.1016/j.jchromb.2011.05.056. Epub 2011 Jun 12.
A novel, rapid and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the simultaneous quantification of gefitinib and its predominant metabolite, O-desmethyl gefitinib in human plasma. Chromatographic separation of analytes was achieved on an Alltima C18 analytical HPLC column (150 mm × 2.1 mm, 5 μm) using an isocratic elution mode with a mobile phase comprised acetonitrile and 0.1% formic acid in water (30:70, v/v). The flow rate was 300 μL/min. The chromatographic run time was 3 min. The column effluents were detected by API 4000 triple quadrupole mass spectrometer using electrospray ionization (ESI) in positive mode. Linearity was demonstrated in the range of 5-1000 ng/mL for gefitinib and 5-500 ng/mL for O-desmethyl gefitinib. The intra- and inter-day precisions for gefitinib and O-desmethyl gefitinib were ≤10.8% and the accuracies ranged from 89.7 to 104.7% for gefitinib and 100.4 to 106.0% for O-desmethyl gefitinib. This method was used as a bioanalytical tool in a phase I clinical trial to investigate the possible effect of hydroxychloroquine on the pharmacokinetics of gefitinib. The results of this study enabled clinicians to ascertain the safety of the combination therapy of hydroxychloroquine and gefitinib in patients with advanced (Stage IIIB-IV) non-small cell lung cancer (NSCLC).
建立并验证了一种新颖、快速且特异的液相色谱-串联质谱（LC-MS/MS）法，用于同时定量测定人血浆中的吉非替尼及其主要代谢物 O-去甲基吉非替尼。在 Alltima C18 分析型 HPLC 柱（150mm×2.1mm，5μm）上，采用等度洗脱模式，以乙腈和 0.1%甲酸水溶液（30:70，v/v）作为流动相，实现了分析物的色谱分离。流速为 300μL/min。色谱运行时间为 3min。采用 API 4000 三重四极杆质谱仪，以正离子电喷雾电离（ESI）模式进行检测。吉非替尼和 O-去甲基吉非替尼的线性范围分别为 5-1000ng/mL 和 5-500ng/mL。吉非替尼和 O-去甲基吉非替尼的日内和日间精密度均≤10.8%，准确度分别为 89.7-104.7%和 100.4-106.0%。该方法被用作一项 I 期临床试验中的生物分析工具，以研究羟氯喹对吉非替尼药代动力学的可能影响。该研究结果使临床医生能够确定羟氯喹与吉非替尼联合治疗晚期（ⅢB 期-IV 期）非小细胞肺癌（NSCLC）患者的安全性。
