Simple determination and quantification of tofacitinib, a JAK inhibitor, in rat plasma, urine and tissue homogenates by
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Journal of Pharmaceutical Investigation https://doi.org/10.1007/s40005-020-00490-z
ORIGINAL ARTICLE
Simple determination and quantification of tofacitinib, a JAK inhibitor, in rat plasma, urine and tissue homogenates by HPLC and its application to a pharmacokinetic study Ji Eun Kim1 · Mun Young Park1 · So Hee Kim2 Received: 20 December 2019 / Accepted: 28 April 2020 © The Korean Society of Pharmaceutical Sciences and Technology 2020
Abstract Purpose Tofacitinib, a janus kinase (JAK) inhibitor, was developed for the treatment of rheumatoid arthritis. To evaluate its pharmacokinetic characteristics, a simple method of quantifying tofacitinib by high-performance liquid chromatography (HPLC) was developed to estimate its concentrations in rat plasma, urine and tissue homogenates. Methods Hydrocortisone was used as an internal standard. The mobile phase was an isocratic system of acetonitrile: 10 mM ammonium acetate, pH 5.0 (30.5:69.5, v/v), and the flow rate was 1.0 mL/min. Chromatograms were monitored by a UV detector at 287 nm. The retention times for tofacitinib and hydrocortisone were 7.21 and 11.3 min, respectively. Results The lower limits of quantification for tofacitinib in rat plasma and urine were 0.01 and 0.1 μg/mL, respectively. The intraday assay precisions (coefficients of variation) were generally low; 3.69–5.88% for rat plasma and 4.21–6.18% for rat urine. The corresponding values of interday assay precisions were 5.06% and 5.46%, respectively. Accuracies ranged from 92.9 to 107%, with no interference by endogenous substances. Tofacitinib has a short half-life (39.0 min) and was widely distributed in rat tissues. Conclusion This HPLC method is very simple and sensitive and can be applied to future preclinical and clinical investigations of tofacitinib. Keywords Tofacitinib · JAK 3 inhibitor · HPLC · Validation · Pharmacokinetics
Introduction Autoimmune reactions are responsible for various diseases and the rejection of transplanted organs, leading to the development of immunosuppressive drugs. One of the major molecular pathways associated with autoimmunity is a janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathway (Boor et al. 2017; Martina et al. 2016). Tofacitinib (3-[(3R, 4R)-4-methyl3-[methyl-(7H-pyrrolo[2,3-day]pyrimidin-4-yl)amino] * So Hee Kim [email protected] 1
Graduate School of Global Pharmaceutical Industry and Clinical Pharmacy, Ajou University, 206 Worldcup‑ro, Yeongtong‑gu, Suwon 16499, Republic of Korea
College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, 206 Worldcup‑ro, Yeongtong‑gu, Suwon 16499, Republic of Korea
2
piperidin-1-yl]-3-oxopropaneni-tril, Fig. 1) is a novel, potent and selective JAK1/JAK3 inhibitor that blocks signaling through receptors for several cytokines, including interleukins-2, -4, -7, -9, -15 and -21 and modulates various aspects of immune responses (Dowty et al. 2014a). Tofacitinib has been approved for the treatment of patients with several autoimmune
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