Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
Simple and sensitive HPLC-UV method for determination of bexarotene in rat plasma
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DOI：
10.1016/j.jchromb.2016.11.024
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发表时间：
2017-01-01
影响因子：
3
通讯作者：
Gershkovich, Pavel
中科院分区：
文献类型：
--
作者：
Lee, Jong Bong;Zgair, Atheer;Gershkovich, Pavel
贝沙罗汀目前已上市用于治疗皮肤T细胞淋巴瘤，其对其他癌症的治疗效果也越来越受到关注。贝沙罗汀的神经保护作用也有报道。在这项研究中，一个简单的，灵敏的和成本效益的生物分析方法测定贝沙罗汀在大鼠血浆中的开发和充分验证。该方法采用乙腈沉淀蛋白质，并用正己烷-乙酸乙酯（10：1，v/v）进行液-液萃取。采用沃茨Atlantis C18色谱柱，乙腈-醋酸铵缓冲液（10 mM，pH 4.1）为移动的相，体积比为75：25（v/v），流速为0.2 mL/min。通过波长设定为259 nm的UV检测器观察色谱图。进行了日内和日间验证，并在各种条件下进行了样品稳定性试验。大鼠药代动力学研究证明了该方法的适用性。对大鼠静脉推注2.5 mg/kg剂量，并在预定时间点采集样品。因此，获得了AUC（inf）（4668 +/- 452 h ng/mL）、C-0（6219 +/- 1068 ng/mL）和t（1/2）（1.15 +/- 0.02 h）的药代动力学参数。此外，将开发的方法进一步应用于人和小鼠血浆，以评估该方法对其他种属样品的适用性。(C)2016爱思唯尔B. V.保留所有权利。
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 AUC(inf) (4668 +/- 452 h ng/mL), C-0 (6219 +/- 1068 ng/mL) and t(1/2) (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. (C) 2016 Elsevier B.V. All rights reserved.