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Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma

Lee, Jong Bong; Zgair, Atheer; Kim, Tae Hwan; Kim, Min Gi; Yoo, Sun Dong; Fischer, Peter M.; Gershkovich, Pavel

Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma Thumbnail


Authors

Jong Bong Lee

Atheer Zgair

Tae Hwan Kim

Min Gi Kim

Sun Dong Yoo

Peter M. Fischer



Abstract

Bexarotene is currently marketed for treatment of cutaneous T-cell lymphoma and there has been growing interest in its therapeutic effectiveness for other cancers. Neuroprotective effects of bexarotene have also been reported. In this study, a simple, sensitive and cost-efficient bioanalytical method for determination of bexarotene in rat plasma was developed and fully validated. The method utilises protein precipitation with acetonitrile and liquid-liquid extraction with n-hexane-ethyl acetate (10:1, v/v). An HPLC-UV system with a Waters Atlantis C18 column and a mobile phase of acetonitrile-ammonium acetate buffer (10 mM, pH 4.1) at a ratio of 75:25 (v/v), flow rate 0.2 mL/min was used. Chromatograms were observed by a UV detector with wavelength set to 259 nm. Intra- and inter-day validations were performed and sample stability tests were conducted at various conditions. The applicability of the method was demonstrated by a pharmacokinetic study in rats. Intravenous bolus dose of 2.5 mg/kg was administered to rats and samples were obtained at predetermined time points. As a result, pharmacokinetic parameters of AUCinf (4668 ± 452 h ng/mL), C0 (6219 ± 1068 ng/mL) and t1/2 (1.15 ± 0.02 h) were obtained. In addition, the developed method was further applied to human and mouse plasma to assess the suitability of the method for samples from other species.

Citation

Lee, J. B., Zgair, A., Kim, T. H., Kim, M. G., Yoo, S. D., Fischer, P. M., & Gershkovich, P. (2017). Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma. Journal of Chromatography B, 1040, 73-80. https://doi.org/10.1016/j.jchromb.2016.11.024

Journal Article Type Article
Acceptance Date Nov 16, 2016
Online Publication Date Nov 17, 2016
Publication Date Jan 1, 2017
Deposit Date Jan 17, 2017
Publicly Available Date Mar 28, 2024
Journal Journal of Chromatography B
Print ISSN 1570-0232
Electronic ISSN 1570-0232
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 1040
Pages 73-80
DOI https://doi.org/10.1016/j.jchromb.2016.11.024
Keywords Bexarotene; HPLC-UV; Preclinical pharmacokinetics; Rat plasma; Human plasma; Mouse plasma
Public URL https://nottingham-repository.worktribe.com/output/830728
Publisher URL http://dx.doi.org/10.1016/j.jchromb.2016.11.024
Additional Information This article is maintained by: Elsevier; Article Title: Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma; Journal Title: Journal of Chromatography B; CrossRef DOI link to publisher maintained version: https://doi.org/10.1016/j.jchromb.2016.11.024; Content Type: article; Copyright: © 2016 Elsevier B.V. All rights reserved.

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