Department of Medicinal Therapy Research, Pharmaceutical Education and Research Center, Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo 204-8588, Japan.
J Chromatogr Sci. 2024 Jul 10;62(6):580-584. doi: 10.1093/chromsci/bmad082.
Ivosidenib is used for the treatment of acute myeloid leukemia (AML) with isocitrate dehydrogenase 1 (IDH1) mutations. However, increased blood concentrations of ivosidenib are associated with a risk of a prolonged QT interval in patients with AML. Therapeutic drug monitoring in patients with AML with IDH1 mutation offers the potential to improve treatment efficacy while minimizing toxicity. In this study, we developed an efficient high-performance liquid chromatography-ultraviolet (HPLC-UV) method for the quantification of ivosidenib in plasma. Human plasma samples (50 μL) were processed by protein precipitation using acetonitrile, followed by chromatographic separation on a reversed-phase column with an isocratic mobile phase of 0.5% KH₂PO₄ (pH 4.5) and acetonitrile (45:55, v/v) at a flow rate of 1.0 mL/min, with ultraviolet detection at 245 nm. Calibration curves were linear over the range of 0.25-20 μg/mL with a coefficient of determination (r2) of 0.99999. Intra-day and inter-day precision were 1.20-8.04% and 0.69-4.20%, respectively. The assay accuracy was -2.00% to 1.93% and recovery was >91.2%. These findings support the effectiveness of the newly developed HPLC-UV method for the quantification of ivosidenib in human plasma. This simple and cost-effective method is expected to expand ivosidenib monitoring in laboratories lacking LC-MS/MS instruments.
依维莫司用于治疗异柠檬酸脱氢酶 1（IDH1）突变的急性髓系白血病（AML）。然而，AML 患者血液中依维莫司浓度增加与 QT 间期延长的风险相关。对 IDH1 突变的 AML 患者进行治疗药物监测有潜力提高治疗效果，同时最小化毒性。在这项研究中，我们开发了一种高效的 HPLC-UV 方法，用于定量测定血浆中的依维莫司。用乙腈对 50 μL 人血浆样品进行蛋白沉淀处理，然后在反相柱上进行色谱分离，流动相为 0.5% KH2PO4（pH 4.5）和乙腈（45:55，v/v）的等度洗脱，流速为 1.0 mL/min，紫外检测波长为 245nm。校准曲线在 0.25-20μg/mL 范围内呈线性，相关系数（r2）为 0.99999。日内和日间精密度分别为 1.20-8.04%和 0.69-4.20%。测定准确度为-2.00%至 1.93%，回收率>91.2%。这些发现支持新开发的 HPLC-UV 方法用于定量测定人血浆中的依维莫司的有效性。这种简单且具有成本效益的方法有望在缺乏 LC-MS/MS 仪器的实验室中扩大依维莫司监测。
