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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

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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.

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Acknowledgements

This research was supported by Korea Health Technology R&D Project (HI16C0992), through Korea Health Industry Development Institute (KHIDI), which is funded by the Ministry of Health & Welfare, Republic of Korea.

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Authors and Affiliations

  1. Graduate School of Global Pharmaceutical Industry and Clinical Pharmacy, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea

    Ji Eun Kim & Mun Young Park

  2. College of Pharmacy and Research Institute of Pharmaceutical Science and Technology, Ajou University, 206 Worldcup-ro, Yeongtong-gu, Suwon, 16499, Republic of Korea

    So Hee Kim

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  1. Ji Eun Kim
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Correspondence to So Hee Kim.

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All authors (Kim JE, Park MY and Kim SH) declare that they have no conflict of interest.

Statement of human and animal rights

All experimental procedures and protocols were reviewed and approved by the Institutional Animal Care and Use Committee of the Laboratory Animal Research Center of Ajou University Medical Center (IACUC No. 2017-0074, 2018) (Suwon, Republic of Korea).

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Kim, J.E., Park, M.Y. & Kim, S.H. 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. J. Pharm. Investig. 50, 603–612 (2020). https://doi.org/10.1007/s40005-020-00490-z

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