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Peer-reviewedCC BY-NCBiological and Pharmaceutical Bulletin

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

Abstract

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.

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BibTeX
@article{yamaguchi2026simple,
  title = {{Simple LC-MS/MS Method for Ruxolitinib in Human Plasma and Its Clinical Application in Pediatric and Adult Patients}},
  author = {Atsushi Yamaguchi and Yuki Tazawa and Shunsuke Nashimoto and Masahiro Ueki and Shinsuke Hirabayashi and Souichi Shiratori and Fuyo Takeda and Keisuke Kagami and Atsushi Manabe and Takanori Teshima and Mitsuru Sugawara and Yoh Takekuma},
  journal = {Biological and Pharmaceutical Bulletin},
  year = {2026},
  month = sep,
  doi = {10.1248/bpb.b26-00243},
  url = {https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00243/_article},
  note = {CC BY-NC},
}
RIS
TY  - JOUR
TI  - Simple LC-MS/MS Method for Ruxolitinib in Human Plasma and Its Clinical Application in Pediatric and Adult Patients
AU  - Atsushi Yamaguchi
AU  - Yuki Tazawa
AU  - Shunsuke Nashimoto
AU  - Masahiro Ueki
AU  - Shinsuke Hirabayashi
AU  - Souichi Shiratori
AU  - Fuyo Takeda
AU  - Keisuke Kagami
AU  - Atsushi Manabe
AU  - Takanori Teshima
AU  - Mitsuru Sugawara
AU  - Yoh Takekuma
PY  - 2026
DA  - 2026/09/18
JO  - Biological and Pharmaceutical Bulletin
DO  - 10.1248/bpb.b26-00243
UR  - https://www.jstage.jst.go.jp/article/bpb/49/9/49_b26-00243/_article
AB  - 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.
SN  - 1347-5215
SN  - 0918-6158
ER  -