Laboratoire de Pharmacologie-Toxicologie, Service de Pharmacie, GH Cochin - Hôtel Dieu - Broca, AP-HP, Paris, France.
J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Aug 1;879(23):2345-50. doi: 10.1016/j.jchromb.2011.06.026. Epub 2011 Jun 22.
Gefitinib and erlotinib are two oral tyrosine kinase inhibitors (TKI) approved for the treatment of advanced non-small cell lung cancer (NSCLC). Published methods for simultaneous analysis of erlotinib and gefitinib in plasma are exclusively based on mass spectrometry. The purpose of this study was to develop a simple and sensitive HPLC-UV method to simultaneously quantify these two TKI in plasma. Following liquid-liquid extraction, gefitinib, erlotinib and sorafenib (internal standard), were separated with gradient elution (on a C8+ Satisfaction(®) using a mobile phase of acetonitrile/20mM ammonium acetate pH 4.5). Samples were eluted at a flow rate of 0.4 ml/min throughout the 15-min run. Dual UV wavelength mode was used, with gefitinib and erlotinib monitored at 331 nm, and sorafenib at 249 nm. The calibration was linear in the range 20-1000 ng/ml and 80-4000 ng/ml for gefitinib and erlotinib, respectively. Inter- and intra-day imprecision were less than 7.2% and 7.6% for gefitinib and erlotinib, respectively. This analytical method was successfully applied to assess the steady state plasma exposure to these TKI in NSCLC patients. This simple, sensitive, accurate and cost-effective method can be used in routine clinical practice to monitor gefitinib or erlotinib concentrations in plasma from NSCLC patients.
吉非替尼和厄洛替尼是两种已被批准用于治疗晚期非小细胞肺癌（NSCLC）的口服酪氨酸激酶抑制剂（TKI）。目前已发表的用于同时分析血浆中厄洛替尼和吉非替尼的方法均完全基于质谱法。本研究旨在开发一种简单、灵敏的 HPLC-UV 方法，用于同时定量检测这两种 TKI 在血浆中的浓度。经过液液萃取后，吉非替尼、厄洛替尼和索拉非尼（内标）在 C8+ Satisfaction(®)柱上，采用梯度洗脱（流动相为乙腈/20mM 乙酸铵 pH4.5）进行分离。样品在 15 分钟的运行过程中以 0.4ml/min 的流速洗脱。采用双紫外波长模式，吉非替尼和厄洛替尼在 331nm 处检测，索拉非尼在 249nm 处检测。吉非替尼和厄洛替尼的校准范围分别为 20-1000ng/ml 和 80-4000ng/ml，线性良好。吉非替尼和厄洛替尼的日内和日间精密度均小于 7.2%和 7.6%。该分析方法已成功应用于评估 NSCLC 患者中这些 TKI 的稳态血浆暴露情况。这种简单、灵敏、准确且具有成本效益的方法可用于常规临床实践，以监测 NSCLC 患者血浆中吉非替尼或厄洛替尼的浓度。
