Simple LC-MS/MS Method for Ruxolitinib in Human Plasma and Its Clinical Application in Pediatric and Adult Patients

Ruxolitinib is a Janus kinase inhibitor effective against graft-versus-host disease and hemophagocytic lymphohistiocytosis. However, clinical management is challenged by potential drug-drug interactions and adverse events. Although therapeutic drug monitoring (TDM) can optimize drug safety and efficacy, real-world pharmacokinetic data are limited. To address this gap, we established a simple and sensitive LC-MS/MS method with a total run time of 8.1 min. The method demonstrated linearity over a range of 0.5-100 ng/mL. The intra- and inter-day precision and accuracy met the acceptance criteria. The method was successfully applied to 8 pediatric and 10 adult patients. Measurable concentrations were confirmed in infants (<2 years). The observed trough concentrations varied widely, ranging from 0.69 to 22.2 ng/mL in pediatric patients and <0.5 to 80.6 ng/mL in adult patients. Notably, an intraindividual comparison in one adult case revealed that posaconazole co-administration increased the trough concentration by approximately 4-fold and the area under the plasma concentration-time curve by approximately 2-fold, compared with the period without azoles. In conclusion, we established a validated LC-MS/MS method that was applicable to the measurement of ruxolitinib concentrations in pediatric and adult patients in this single-center study. This method may contribute to the accumulation of pharmacokinetic data for future evaluation of TDM strategies.