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

Lee, Jong Bong and Zgair, Atheer and Kim, Tae Hwan and Kim, Min Gi and Yoo, Sun Dong and Fischer, Peter M. and Gershkovich, Pavel (2017) Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma. Journal of Chromatography B, 1040 . pp. 73-80. ISSN 1570-0232

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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.

Item Type: Article
Keywords: Bexarotene; HPLC-UV; Preclinical pharmacokinetics; Rat plasma; Human plasma; Mouse plasma
Schools/Departments: University of Nottingham, UK > Faculty of Science > School of Pharmacy
Identification Number: 10.1016/j.jchromb.2016.11.024
Depositing User: Eprints, Support
Date Deposited: 17 Jan 2017 09:12
Last Modified: 19 Nov 2017 18:41
URI: http://eprints.nottingham.ac.uk/id/eprint/39892

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