Yasu Takeo, Momo Kenji, Kobayashi Shunsuke, Kuroda Seiichirou, Tojo Arinobu
Department of Pharmacy, The Research Hospital, The Institute of Medical Science, The University of Tokyo.
Faculty of Pharmaceutical Sciences, Teikyo Heisei University.
Biol Pharm Bull. 2018 Feb 1;41(2):254-258. doi: 10.1248/bpb.b17-00806. Epub 2017 Dec 6.
Ponatinib, a novel tyrosine kinase inhibitor marketed in 2016, is a key drug used for treating chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia. This study aimed to develop a simple method for determining plasma ponatinib concentration. The analysis required extraction of a 400-µL sample of plasma and precipitation of proteins using an Oasis HLB cartridge. Ponatinib and bosutinib, which is used as an internal standard, were separated by HPLC using a mobile phase of acetonitrile : 0.037 mol/L KHPO (pH 4.5) (39 : 61, v/v) on a Capcell Pack C18 MG II (25×4.6 mm) monitored at 250 nm, with a flow rate of 1.0 mL/min. This assay method was then used for determining plasma ponatinib concentration in a 42-year-old man treated with ponatinib at 15 mg/d. The calibration curve was found to be linear for the plasma concentration range of 5-250 ng/mL with a regression coefficient (r) of 0.9999. The coefficients of intra-day and inter-day validation under these concentrations were 2.1-6.0 and 4.5-8.0%, respectively. The assay accuracy was -1.5-9.0%, and the recovery was greater than 86%. The plasma concentration of the patient at 2.5 and 3 h after 15 mg ponatinib administration was 43.6 and 49.3 ng/mL, respectively. This method of HPLC equipped with UV detection for determining plasma ponatinib concentration has several advantages, such as simplicity and applicability to routine therapeutic drug monitoring at hospital laboratories.
波纳替尼是2016年上市的一种新型酪氨酸激酶抑制剂，是治疗慢性髓性白血病和费城染色体阳性急性淋巴细胞白血病的关键药物。本研究旨在开发一种简单的方法来测定血浆中波纳替尼的浓度。该分析需要提取400μL血浆样本，并使用Oasis HLB柱进行蛋白质沉淀。波纳替尼和用作内标的博舒替尼通过高效液相色谱法（HPLC）分离，在Capcell Pack C18 MG II（25×4.6mm）柱上，以乙腈∶0.037mol/L KHPO（pH 4.5）（39∶61，v/v）为流动相，于250nm波长处进行监测，流速为1.0mL/min。然后将该测定方法用于测定一名42岁男性患者的血浆波纳替尼浓度，该患者接受波纳替尼治疗，剂量为15mg/d。发现校准曲线在血浆浓度范围5 - 250ng/mL内呈线性，回归系数（r）为0.9999。在这些浓度下，日内和日间验证的系数分别为2.1 - 6.0%和4.5 - 8.0%。测定准确度为 - 1.5 - 9.0%，回收率大于86%。给予15mg波纳替尼后2.5小时和3小时患者的血浆浓度分别为43.6和49.3ng/mL。这种配备紫外检测的HPLC法测定血浆波纳替尼浓度具有几个优点，如简单且适用于医院实验室的常规治疗药物监测。
