title: Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma.
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 (10mM, pH 4.1) at a ratio of 75:25 (v/v), flow rate 0.2mL/min was used. Chromatograms were observed by a UV detector with wavelength set to 259nm. 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 2.5mg/kg was administered to rats and samples were obtained at predetermined time points. As a result, pharmacokinetic parameters of AUCinf(4668±452hng/mL), C0(6219±1068ng/mL) and t1/2(1.15±0.02h) 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.
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Jong Bong
authors.initials: JB
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom; College of Pharmacy, University of Anbar, Anbar, Iraq.
authors.forename: Atheer
authors.initials: A
authors.lastname: Zgair
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea.
authors.forename: Tae Hwan
authors.initials: TH
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea.
authors.forename: Min Gi
authors.initials: MG
authors.lastname: Kim
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea.
authors.forename: Sun Dong
authors.initials: SD
authors.lastname: Yoo
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Fischer
authors.affiliation: School of Pharmacy, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham, NG7 2RD, United Kingdom. Electronic address: Pavel.Gershkovich@nottingham.ac.uk.
authors.forename: Pavel
authors.initials: P
authors.lastname: Gershkovich
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood*; D000077610:Bexarotene; D011232:Chemical Precipitation; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006586:Hexanes / Q000737:chemistry; D006801:Humans; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D016410:Lymphoma, T-Cell, Cutaneous / Q000097:blood / Q000188:drug therapy; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D013764:Tetrahydronaphthalenes / Q000097:blood*
chemical_list: D000970:Antineoplastic Agents; D006586:Hexanes; D018696:Neuroprotective Agents; D013764:Tetrahydronaphthalenes; C026385:n-hexane; D000077610:Bexarotene
keywords: Bexarotene; HPLC-UV; Human plasma; Mouse plasma; Preclinical pharmacokinetics; Rat plasma