Liquid chromatography-mass spectrometric assay for quantitation of the short-chain fatty acid, 2,2-dimethylbutyrate (NSC 741804), in rat plasma
Liquid chromatography-mass spectrometric assay for quantitation of the short-chain fatty acid, 2,2-dimethylbutyrate (NSC 741804), in rat plasma
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DOI：
10.1016/j.jchromb.2007.12.002
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发表时间：
2008-02-01
影响因子：
3
通讯作者：
Egorin, Merrill J.
中科院分区：
文献类型：
--
作者：
Parise, Robert A.;Beumer, Jan H.;Egorin, Merrill J.
2，2-二甲基丁酸酯(DNM)是一种潜在的治疗地中海贫血和血红蛋白疾病的药物。为了便于DMB的药动学评价，我们建立了LC-MS分析方法，并测定了大鼠口服DMB 500 mg/kg后血浆中DMB的浓度。样品经乙腈蛋白沉淀后，将DMB和二甲基戊酸(DMV)内标物衍生化为苯甲酰胺类化合物，用乙腈、水和0.1%甲酸在Hydro-RP柱上进行层析，电喷雾正模电离质谱仪进行检测。该方法的准确度为97-107%，精密度为3.4-6.2%，检测范围为100~10,000 ng/m L。血浆回收率为>；62%。血浆冻融和室温稳定性均可接受。(C)2007 Elsevier B.V.保留所有权利。
2,2-Dimethylbutyrate (DNM) is a potential treatment for thalassemia and hemoglobinopathies. To facilitate pharmacokinetic evaluation of DMB, we developed an LC-MS assay and quantitated DMB in plasma of rats after an oral dose of 500 mg/kg. After acetonitrile protein precipitation, DMB and dimethylvaleric acid (DMV) internal standard were derivatized to benzylamides, chromatographed on a Hydro-RP column with acetonitrile, water, and 0.1% formic acid, and detected by electrospray positive-mode ionization mass spectrometry. The assay was accurate (97-107%) and precise (3.4-6.2%) between 100 and 10,000 ng/mL. Recovery from plasma was >62%. Plasma freeze-thaw and room temperature stability were acceptable. (c) 2007 Elsevier B.V. All rights reserved.