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

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 metho...

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Main Authors: Lee, Jong Bong, Zgair, Atheer, Kim, Tae Hwan, Kim, Min Gi, Yoo, Sun Dong, Fischer, Peter M., Gershkovich, Pavel
Format: Article
Published: Elsevier 2017
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Online Access:https://eprints.nottingham.ac.uk/39892/
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author Lee, Jong Bong
Zgair, Atheer
Kim, Tae Hwan
Kim, Min Gi
Yoo, Sun Dong
Fischer, Peter M.
Gershkovich, Pavel
author_facet Lee, Jong Bong
Zgair, Atheer
Kim, Tae Hwan
Kim, Min Gi
Yoo, Sun Dong
Fischer, Peter M.
Gershkovich, Pavel
author_sort Lee, Jong Bong
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-398922020-05-04T18:23:02Z https://eprints.nottingham.ac.uk/39892/ 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 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. Elsevier 2017-01-01 Article PeerReviewed Lee, Jong Bong, Zgair, Atheer, Kim, Tae Hwan, Kim, Min Gi, Yoo, Sun Dong, 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 Bexarotene; HPLC-UV; Preclinical pharmacokinetics; Rat plasma; Human plasma; Mouse plasma http://dx.doi.org/10.1016/j.jchromb.2016.11.024 doi:10.1016/j.jchromb.2016.11.024 doi:10.1016/j.jchromb.2016.11.024
spellingShingle Bexarotene; HPLC-UV; Preclinical pharmacokinetics; Rat plasma; Human plasma; Mouse 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
title Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
title_full Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
title_fullStr Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
title_full_unstemmed Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
title_short Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
title_sort simple and sensitive hplc-uv method for determination of bexarotene in rat plasma
topic Bexarotene; HPLC-UV; Preclinical pharmacokinetics; Rat plasma; Human plasma; Mouse plasma
url https://eprints.nottingham.ac.uk/39892/
https://eprints.nottingham.ac.uk/39892/
https://eprints.nottingham.ac.uk/39892/