Gas chromatographic–mass spectrometric determination of brain levels of α-cholest-8-en-3β-ol (lathosterol)

Abstract: A gas chromatographic–mass spectrometric (GC–MS) method is proposed for the detection and quantification of lathosterol in rabbit brain. This compound is one of the most important precursors of the cholesterol synthesis. The interest in brain cholesterol metabolism is growing nowadays since it was described to play an important role in some neurodegerative disorders such as Alzheimer''s disease and Multiple Sclerosis. The analytical methodology proposed involves a liquid–liquid extraction procedure (LLE) followed by a silylation step previous to the GC–MS analysis. The chromatographic separation was performed by using a low bleed HP5-MS fused silica capillary column. A clean up is not necessary when using single-ion monitoring (SIM) mode. The molecular ion appears at 458 m/z; being as well the base peak. α-Naphtol was used as an internal standard. The detection limit obtained was 0.09μgmL−1. The method was applied to the determination of brain lathosterol levels in rabbits fed with different types of diets (control and atherogenic, supplemented or not with natural polyphenolic antioxidants). The quantification of the compound in samples showed a reduction, after 1 month, of this precursor of cholesterol synthesis in groups fed with antioxidant supplemented diets. [Copyright &y& Elsevier]