Development and validation of an LC-MS/MS method for ruxolitinib quantification: advancing personalized therapy in hematologic malignancies.

Abstract

Background: 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.

Methods: 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.

Results: The method displayed linearity (R ² > 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.

Conclusion: 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.