title: Liquid chromatography-mass spectrometric assay for quantitation of the short-chain fatty acid, 2,2-dimethylbutyrate (NSC 741804), in rat plasma.
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.
authors.affiliation: Molecular Therapeutics/Drug Discovery Program, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Parise
authors.forename: Jan H
authors.initials: JH
authors.lastname: Beumer
authors.forename: Cyrous O
authors.initials: CO
authors.lastname: Kangani
authors.forename: Julianne L
authors.initials: JL
authors.lastname: Holleran
authors.forename: Julie L
authors.initials: JL
authors.lastname: Eiseman
authors.forename: Nicola F
authors.initials: NF
authors.lastname: Smith
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Covey
authors.forename: Susan P
authors.initials: SP
authors.lastname: Perrine
authors.forename: Merrill J
authors.initials: MJ
authors.lastname: Egorin
mesh_terms: D000818:Animals; D002087:Butyrates / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D051381:Rats; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D002087:Butyrates; C074677:2,2-dimethylbutyric acid