Investigation of Isoprostanes as Potential Biomarkers for Alzheimer's Disease Using Chiral LC-MS/MS and SFC-MS/MS

Victoria      Goss; Amaury      Cazenave-Gassiot; Ashley      Pringle; Anthony      Postle

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that must be diagnosed early to increase drug therapy efficacy. No early definitive diagnostic tool, however, is currently available, thus prompting for the identification of biomarkers of the disease. Isoprostanes (iPs) are prostaglandin-related free radical oxidation products of polyunsaturated fatty acids (PUFA) that are produced under oxidative stress conditions that occur, for instance, in the brain of AD sufferers. iPs are stable lipids known to partition in bodily fluids and are thus interesting potential biomarkers of AD. However, resolution of iPs by reverse phase HPLC is complicated by the existence of multiple regioisomers and enantiomers. Consequently, we have developed two normal phase chiral approaches for the detailed analysis of the F₂-iP class of isoprostanes. First, normal phase chiral LC-MS/MS permitted the identification and quantification of four types of F₂- iPs in urine samples from control, mild cognitive impairment (MCI) patients and severe AD sufferers. Second, given its suitability for non-polar compounds analysis and chiral separations, supercritical fluid chromatography (SFC) was investigated as an alternative approach. SFC-MS/MS enabled the identification of regioisomers and enantiomers of F₂-iPs. Identification of analytes was undertaken by MRM monitoring of diagnostic transitions while the chiral chromatography allowed for the resolution of enantiomers within types. F-iPs could be reproducibly identified and quantified.

Keywords: Supercritical fluid chromatography, SFC, mass spectrometry, chiral separation, isoprostanes, Alzheimer’s disease.

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