Journal of Chromatography B 2008-02-01

Liquid chromatography-mass spectrometric assay for quantitation of the short-chain fatty acid, 2,2-dimethylbutyrate (NSC 741804), in rat plasma.

Robert A Parise, Jan H Beumer, Cyrous O Kangani, Julianne L Holleran, Julie L Eiseman, Nicola F Smith, Joseph M Covey, Susan P Perrine, Merrill J Egorin

Index: J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 862(1-2) , 168-74, (2008)

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Abstract

2,2-Dimethylbutyrate (DMB) 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 500mg/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 10,000ng/mL. Recovery from plasma was >62%. Plasma freeze-thaw and room temperature stability were acceptable.