Mass Spectrometry Research Institute, Beijing Gobroad Hospital, Beijing, China.
Mass Spectrometry Research Institute, Beijing Gobroad Healthcare Group, Beijing, China.
J Pharm Pharm Sci. 2024 Jun 28;27:12905. doi: 10.3389/jpps.2024.12905. eCollection 2024.
Hematologic malignancies such as leukemia and lymphoma present treatment challenges due to their genetic and molecular heterogeneity. Ruxolitinib, a Janus kinase (JAK) inhibitor, has demonstrated efficacy in managing these cancers. However, optimal therapeutic outcomes are contingent upon maintaining drug levels within a therapeutic window, highlighting the necessity for precise drug monitoring.
We developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify ruxolitinib in human plasma, improving upon traditional methods in specificity, sensitivity, and efficiency. The process involved the use of advanced chromatographic techniques and robust mass spectrometric conditions to ensure high accuracy and minimal matrix effects. The study was conducted using samples from 20 patients undergoing treatment, with calibration standards ranging from 10 to 2000 ng/mL.
The method displayed linearity ( > 0.99) across the studied range and proved highly selective with no significant interference observed. The method's precision and accuracy met FDA guidelines, with recovery rates consistently exceeding 85%. Clinical application demonstrated significant variability in ruxolitinib plasma levels among patients, reinforcing the need for individualized dosing schedules.
The validated LC-MS/MS method offers a reliable and efficient tool for the therapeutic drug monitoring of ruxolitinib, facilitating personalized treatment approaches in hematologic malignancies. This approach promises to enhance patient outcomes by optimizing dosing to reduce toxicity and improve efficacy.
由于血液系统恶性肿瘤（如白血病和淋巴瘤）具有遗传和分子异质性，因此在治疗上面临挑战。Janus 激酶（JAK）抑制剂鲁索替尼已被证明在治疗这些癌症方面有效。然而，为了获得最佳的治疗效果，必须将药物水平维持在治疗窗内，这凸显了精确药物监测的必要性。
我们开发了一种灵敏的液相色谱-串联质谱（LC-MS/MS）方法来定量人血浆中的鲁索替尼，该方法在特异性、灵敏度和效率方面优于传统方法。该过程涉及使用先进的色谱技术和强大的质谱条件，以确保高准确性和最小的基质效应。该研究使用了 20 名接受治疗的患者的样本，校准标准品范围为 10 至 2000ng/mL。
该方法在研究范围内表现出线性关系（>0.99），并且高度选择性，没有观察到明显的干扰。该方法的精密度和准确度符合 FDA 指南，回收率始终超过 85%。临床应用表明，患者之间鲁索替尼的血浆水平存在显著差异，这进一步证实了需要制定个体化的给药方案。
验证后的 LC-MS/MS 方法为鲁索替尼的治疗药物监测提供了一种可靠且高效的工具，有助于在血液系统恶性肿瘤中采用个体化治疗方法。这种方法有望通过优化剂量来降低毒性并提高疗效，从而改善患者的治疗效果。
