Laboratory of Inherited Metabolic Disorders, University Hospital and Palacký University in Olomouc, I.P. Pavlova 6, CZ 775 20 Olomouc, Czech Republic.
Clin Chim Acta. 2010 Dec 14;411(23-24):1957-62. doi: 10.1016/j.cca.2010.08.014. Epub 2010 Aug 13.
The aim of this study was to develop, validate and compare flow injection analysis (FIA) and ultra-high-performance liquid chromatography (LC)/tandem mass spectrometry methods for the determination of imatinib in plasma from patients with chronic myeloid leukemia.
The plasma for analysis by both methods was deproteinated by methanol containing d8-imatinib. The separation was achieved on a 1.7 μm C18 column with a linear gradient (4 mM ammonium formiate and acetonitrile, pH 3.2). FIA was performed at flow rate of 0.03 mL/min (0.1% formic acid in methanol). Multiple reaction monitoring mode on the tandem mass spectrometer (API 4000, AB Sciex) in positive ESI were used for detection.
The total analysis times were 3.2 (LC) and 0.75 min (FIA). Both methods were successfully validated and applied to the plasma patients samples. The limits of quantification were 4.1 and 30.8 ng/mL; imprecisions were less than 5.7% and recovery ranged between 93 and 105%, for the LC and FIA, respectively. The methods revealed an agreement with a mean difference of 1.46 ng/mL (SD 28.95 ng/mL).
The high-throughput methods that were developed are suitable for the therapeutic drug monitoring of imatinib in plasma. They can be used in routine clinical practice.
本研究旨在开发、验证和比较流动注射分析（FIA）和超高效液相色谱（LC）/串联质谱法，用于测定慢性髓性白血病患者血浆中的伊马替尼。
两种方法分析的血浆均用含 d8-伊马替尼的甲醇进行脱蛋白处理。分离在 1.7 μm C18 柱上进行，采用线性梯度（4 mM 甲酸铵和乙腈，pH 3.2）。FIA 的流速为 0.03 mL/min（甲醇中 0.1%甲酸）。串联质谱仪（API 4000，AB Sciex）采用正电喷雾多反应监测模式进行检测。
总分析时间分别为 3.2（LC）和 0.75 分钟（FIA）。两种方法均经过验证并应用于患者血浆样本。定量下限分别为 4.1 和 30.8 ng/mL；精密度均小于 5.7%，回收率分别在 93%至 105%之间。两种方法的结果具有一致性，平均差值为 1.46 ng/mL（SD 28.95 ng/mL）。
开发的高通量方法适用于血浆中伊马替尼的治疗药物监测。它们可用于常规临床实践。
