Regular paperDetermination of valproic acid and its metabolites using gas chromatography with mass-selective detection: application to serum and urine samples from sheep

Add time:09/26/2019    Source:sciencedirect.com

An improved method for the quantitative determination of valproic acid (VPA) and sixteen of its metabolites has been developed using gas chromatography-mass spectrometry with selected-ion monitoring. The method is applicable to serum or urine and all metabolites are measured in a single chromatographic run of 29.5 min. Ions selected for quantitative purposes were the characteristic [M-57]+ ions of the tert.-butyldimethylsilyl (tBDMS) derivatives. The method utilizes heptadeuterated VPA as well as six heptadeuterated metabolites as internal standards [i.e. 2-[2H7]propyl-2-pentenoic acid (2-ene[2H7]VPA), 2-[2H7]propyl-4-pentenoic acid (4-ene[2H7]VPA), 2-[2H7]propyl-3-oxopentanoic acid (3-keto[2H7]VPA), 2-[2H7]propyl-4-oxopentanoic acid (4-keto[2H7]VPA), 2-[2H7]propyl-3-hydroxypentanoic acid (3-OH[2H7]VPA), 2-[2H7]propyl-5-hydroxypentanoic acid (5-OH[2H7]VPA)]. The method demonstrates very good accuracy and precision over a large range of concentrations for VPA and all metabolites measured in both human and sheep biological fluids. The assay was applied to the analysis of VPA and metabolites in serum and urine samples collected from three non-pregnant ewes following intravenous bolus administration of a mixture of VPA and [13C4]VPA. Sheep were observed to produce measurable quantities of the majority of metabolites found in humans, with the notable exception of the di-unsaturated compounds (i.e. 2,3′-diene VPA and 2,4-diene VPA). The pharmacokinetics and metabolism of VPA and [13C4]VPA appear to be equivalent in the sheep model. The elimination half-life of VPA and [13C4] VPA in the ewe were estimated to be approximately 3.5 ± 0.4 and 3.2 ± 0.4 h, respectively.

We also recommend Trading Suppliers and Manufacturers of 4-propyl-4-pentenoic acid (cas 13722-70-8). Pls Click Website Link as below: cas 13722-70-8 suppliers

Prev:Pyruvate uptake is inhibited by valproic acid and metabolites in mitochondrial membranes
Next:ArticlesStereoselective Synthesis of the Diunsaturated Metabolites of Valproic Acid)