Quantification of Monosialogangliosides in Human Plasma Through Chemical Derivatization for Signal Enhancement in LC–ESI-MS
Document Type
Article
Publication Date
7-27-2016
Publication Title
Analytica Chimica Acta
Abstract
Gangliosides are found in abundance in the central nervous system of vertebrates. Their metabolic disruption and dysfunction are associated with various neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. In order to improve our understanding of the etiology of these diseases, analytical ganglioside assays with sufficient specificity and sensitivity in relevant biological matrices are required. In the present work we have developed and validated a reverse-phase ultra-performance liquid chromatography (UPLC)/tandem mass spectrometry (MS) method for determining monosialogangliosides GM1, GM2, and GM3 present in human plasma. Compared with our previous method, this method enhanced, by 15 fold, MS responses of the analytes by employing 2-(2-Pyridilamino)-ethylamine (PAEA) & 4-(4, 6-Dimethoxy-1, 3, 5-triazin-2-yl)-4-methylmorpholinium chloride (DMTMM)-based derivatization. The analytes and internal standards were derivatized with PAEA&DMTMM after extraction from plasma using a protein precipitation procedure. They were then purified using liquid–liquid partitioning. When the samples were then analyzed by UPLC-MS/MS with a multiple reaction monitoring (MRM) mode, we achieved superior sensitivity and specificity. This method was evaluated for extraction recovery, calibration linearity, precision, accuracy, and lower limit of quantification (LLOQ). The validated method was successfully applied to monitor monosialoganglioside levels in the plasma from patients with GM3 synthase deficiency. With significantly increased sensitivity, we have, for the first time, detected a significant amount of GM3 in the affected patients.
Recommended Citation
Huang, Qianyang; Liu, Danting; Xin, Baozhong; Cechner, Karen; Zhou, Xiang; Wang, Heng; and Zhou, Aimin, "Quantification of Monosialogangliosides in Human Plasma Through Chemical Derivatization for Signal Enhancement in LC–ESI-MS" (2016). Chemistry Faculty Publications. 442.
https://engagedscholarship.csuohio.edu/scichem_facpub/442
DOI
10.1016/j.aca.2016.04.043
Volume
929
Comments
The UPLC-MS/MS system used for this study was purchased by a grant from the Major Research Instrumentation Program (MRI) of the National Science Foundation (NSF) under grant number CHE-0923308.