Department of Pharmacy & Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam; Division of Pharmacoepidemiology and Clinical Pharmacology, Science Faculty, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht;, Email:
Department of Pharmacy & Pharmacology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam.
Pharmazie. 2020 Apr 6;75(4):136-141. doi: 10.1691/ph.2020.9150.
Here we describe the development and validation of an LC-MS/MS method for the quantification of imatinib and imatinib-d8 in plasma for the support of a clinical absolute bioavailability microdosing trial. The focus lies on the technical aspects to analyse high concentrations of imatinib and low concentrations of imatinib-d8 that are present simultaneously in study samples, using a single sample processing and analytical method. With the validated assay, imatinib and imatinib-d8 can be quantified simultaneously in ranges from 25.0 - 5,000 ng/mL and 0.01 - 2.0 ng/mL, respectively. The method was successfully applied in an imatinib-d8 absolute bioavailability microdosing trial, where a 100 μg imatinib-d8 microdose was intravenously administered to a patient on oral imatinib treatment 400 mg once daily.
在这里，我们描述了一种用于支持临床绝对生物利用度微剂量试验的 LC-MS/MS 方法的开发和验证，以定量测定血浆中的伊马替尼和伊马替尼-d8。重点在于分析研究样本中同时存在的高浓度伊马替尼和低浓度伊马替尼-d8 的技术方面，使用单一的样品处理和分析方法。使用经过验证的检测方法，可以分别在 25.0-5000ng/mL 和 0.01-2.0ng/mL 的范围内同时定量检测伊马替尼和伊马替尼-d8。该方法已成功应用于伊马替尼-d8 绝对生物利用度微剂量试验中，在该试验中，一名每天口服伊马替尼 400mg 的患者静脉注射 100μg 伊马替尼-d8 微剂量。
