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

Abstract

Abstract2,2-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 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.

Divergent Effectiveness of Multispecies Probiotic Preparations on Intestinal Microbiota Structure Depends on Metabolic Properties

“…SCFAs in fecal samples of mice were measured using liquid chromatography-mass spectrometry as described by [ 16 ] using a LTQ-FT system (Thermo Scientific™) equipped with a Phenomenex Synergi Polar-RP column (Phenomenex, Torrance, CA, USA). The results are calculated in nmol/mg of fecal sample.…”

New method for GC/FID and GC–C-IRMS analysis of plasma free fatty acid concentration and isotopic enrichment

“…Amides are more hydrolytically stable and, due to higher polarity elute at higher temperature (Δ +10 to +20 °C) than their corresponding methyl ester. Both of these properties would be advantageous for assessment of short chain fatty acids [20]. Although amide derivatives such as pyrrolidides, picolinyl esters and dimethyloxazolines (DMOX) of fatty acids have been used for mass spectrometric determination of double bond positions in polyunsaturated fatty acids, these have not been widely adopted due to lack of a simple, mild and efficient derivatization methodology [21], [22], [23], [24], [25] with the exception of picolinyl esters derivatives [26].…”

A Concise Review of Liquid Chromatography-Mass Spectrometry-Based Quantification Methods for Short Chain Fatty Acids as Endogenous Biomarkers

“…In an early study Parise et al quantified 2,2-dimethylbutyrate (DMB) in rat plasma following derivatization to benzylamide [ 70 ]. DMB and other branched SCFAs are promising drug candidates for hemoglobinopathies and have been shown to stimulate fetal globin and erythropoiesis in multiple species [ 79 , 80 , 81 , 82 , 83 ].…”