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

  • J Chromatogr B Analyt Technol Biomed Life Sci. 2008 Feb 1;862(1-2):168-74. doi: 10.1016/j.jchromb.2007.12.002.
Robert A Parise  1 ,  Jan H Beumer ,  Cyrous O Kangani ,  Julianne L Holleran ,  Julie L Eiseman ,  Nicola F Smith ,  Joseph M Covey ,  Susan P Perrine ,  Merrill J Egorin
Affiliations
  • 1. Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
PMID: 18155649 DOI: 10.1016/j.jchromb.2007.12.002
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.

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