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.

中文翻译：

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测定人血浆中 Ivosidenib 的简单 HPLC-UV 方法

Ivosidenib 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，ivosidenib 血药浓度升高与 AML 患者 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可能提高治疗效果，同时最大限度地降低毒性。在本研究中，我们开发了一种高效的高效液相色谱-紫外 (HPLC-UV) 方法，用于定量血浆中的 ivosidenib。使用乙腈对人血浆样品 (50 μL) 进行蛋白质沉淀处理，然后使用 0.5% KH2PO4 (pH 4.5) 和乙腈 (45:55，v/v) 等度流动相在反相柱上进行色谱分离，温度为流速1.0 mL/min，紫外检测245 nm。校准曲线在 0.25–20 μg/mL 范围内呈线性，确定系数 (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 方法对人血浆中 ivosidenib 定量的有效性。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 ivosidenib 监测范围。