Yasu Takeo, Momo Kenji, Yasui Hiroshi, Kuroda Seiichirou
Department of Pharmacy, The Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Department of Hematology/Oncology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Biomed Chromatogr. 2019 Mar;33(3):e4435. doi: 10.1002/bmc.4435. Epub 2018 Dec 11.
Ibrutinib is an oral inhibitor of Bruton tyrosine kinase, which is one of the key drugs used for the treatment of chronic lymphocytic leukemia and mantle cell lymphoma. In this study, we aimed to develop a simple method for determining plasma ibrutinib concentration. The analysis required extraction of a 200 μL plasma sample and precipitation of proteins using solid-phase extraction. Ibrutinib and nilotinib, which was used as an internal standard, were separated using high-performance liquid chromatography (HPLC) using a mobile phase of acetonitrile-0.5% monopotassium phosphate (KH PO , pH 3.0; 52:48, v/v) on a Capcell Pack C MG II (250 × 4.6 mm) monitored at 260 nm, at a flow rate of 1.0 mL/min. The calibration curve was linear at the plasma concentration range of 10-500 ng/mL with a coefficient of determination (r ) of 0.9999. The coefficients of intra-day and inter-day validation were 4.0-6.6 and 2.6-7.7%, respectively. The assay accuracy was -4.4-8.6%, and the recovery was >84%. This HPLC method coupled with ultraviolet (UV) detection for determining ibrutinib plasma concentration has several advantages such as simplicity and applicability to routine therapeutic drug monitoring at hospital laboratories.
依鲁替尼是布鲁顿酪氨酸激酶的口服抑制剂，是用于治疗慢性淋巴细胞白血病和套细胞淋巴瘤的关键药物之一。在本研究中，我们旨在开发一种简单的方法来测定血浆依鲁替尼浓度。该分析需要提取200μL血浆样品，并使用固相萃取沉淀蛋白质。使用乙腈 - 0.5%磷酸二氢钾（KH₂PO₄，pH 3.0；52:48，v/v）作为流动相，在Capcell Pack C18 MG II（250×4.6 mm）上，于260 nm波长、1.0 mL/min流速下，通过高效液相色谱（HPLC）分离依鲁替尼和用作内标的尼洛替尼。校准曲线在10 - 500 ng/mL的血浆浓度范围内呈线性，决定系数（r²）为0.9999。日内和日间验证系数分别为4.0 - 6.6%和2.6 - 7.7%。测定准确度为 - 4.4 - 8.6%，回收率>84%。这种结合紫外（UV）检测的HPLC方法用于测定依鲁替尼血浆浓度具有多种优点，如简单且适用于医院实验室的常规治疗药物监测。
