Method Development for Mass Spectrometric Detection of Neurosteroids in Cerebrospinal Fluid as Potential Biomarkers of Cognitive Disorders [thesis]

Juliane Teubel, Universitätsbibliothek Der FU Berlin
Neurosteroids (NS) are a special of group of endogenous steroids, which are synthesized in the central (CNS) or peripheral nervous system (PNS), which is not only a source but also a target for NS. As they are discussed as potential biomarkers for various cognitive disorders, research interest in this topic remarkably increases. In this context CSF becomes an interesting specimen for NS analysis, as it is the only accessible matrix which most likely reflects brain metabolism in living human
more » ... gs. Analysis of NS is truly challenging for different reasons, such as low amounts of available matrix, ultra-trace-levels of expected steroids, and high structural similarity of endogenous steroids. Therefore, the aim of this work was the development of a comprehensive and sensitive method for profiling of an as large as possible set of NS in one aliquot of human CSF. For method development and evaluation, a set of fifty-one steroids, including (pro-)gestagens, androgens, corticoids, estrogens and steroid sulfates was selected, based on comprehensive literature research of neurosteroids already determined in human CSF and expanded with steroids covering major peripheral pathways of biosynthesis and metabolism. Profiling of endogenous steroids is well-established with gas chromatography (tandem) mass spectrometry (GC-MS(/MS)), (ultra) high performance liquid chromatography (tandem) mass spectrometry ((U)HPLC-MS(/MS)), or immunoassays (IA) – each method offering different advantages or disadvantages. As IA, HPLC and GC based methods were reported for ascending number of analytes that were detected, GC-MS was initially selected within this project regarding the selected large set of analytes. Analysis with GC-MS requires derivatization of analytes, therefore several well-established derivatization procedures were examined. Overall, none of the derivatization procedures provided acceptable results for further method development and analyte quantification, due to formation of multiple derivatives of some steroids and occurrenc [...]
doi:10.17169/refubium-29479 fatcat:oxn3res6dfc4rnrmhengggq73u