title: A new liquid chromatography/tandem mass spectrometry method for quantification of gangliosides in human plasma.
abstract: Gangliosides are a family of glycosphingolipids characterized by mono- or polysialic acid-containing oligosaccharides linked through 1,3- and 1,4-β glycosidic bonds with subtle differences in structure that are abundantly present in the central nervous systems of many living organisms. Their cellular surface expression and physiological malfunction are believed to be pathologically implicated in considerable neurological disorders, including Alzheimer and Parkinson diseases. Recently, studies have tentatively elucidated that mental retardation or physical stagnation deteriorates as the physiological profile of gangliosides becomes progressively and distinctively abnormal during the development of these typical neurodegenerative syndromes. In this work, a reverse-phase liquid chromatography/tandem mass spectrometry (LC/MS/MS) assay using standard addition calibration for determination of GM2, GM3, GD2, and GD3 in human plasma has been developed and validated. The analytes and internal standard were extracted from human plasma using a simple protein precipitation procedure. Then the samples were analyzed by reverse-phase ultra-performance liquid chromatography (UPLC)/MS/MS interfaced to mass spectrometry with electrospray ionization using a multiple reaction monitoring mode to obtain superior sensitivity and specificity. This assay was validated for extraction recovery, calibration linearity, precision, and accuracy. Our quick and sensitive method can be applied to monitor ganglioside levels in plasma from normal people and neurodegenerative patients.
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Qianyang
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA. Electronic address: x.zhou34@csuohio.edu.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA.
authors.forename: Danting
authors.initials: D
authors.lastname: Liu
authors.affiliation: DDC Clinic, Center for Special Needs Children, Middlefield, OH 44062, USA.
authors.forename: Baozhong
authors.initials: B
authors.lastname: Xin
authors.affiliation: DDC Clinic, Center for Special Needs Children, Middlefield, OH 44062, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Cechner
authors.affiliation: DDC Clinic, Center for Special Needs Children, Middlefield, OH 44062, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical Chemistry Program, Department of Chemistry, Cleveland State University, Cleveland, OH 44115, USA; Center for Gene Regulation in Health and Diseases, Cleveland State University, Cleveland, OH 44115, USA. Electronic address: a.zhou@csuohio.edu.
authors.forename: Aimin
authors.initials: A
authors.lastname: Zhou
mesh_terms: D002138:Calibration; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D002853:Chromatography, Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D004827:Epilepsy / Q000097:blood; D005260:Female; D005679:G(M3) Ganglioside / Q000097:blood; D005732:Gangliosides / Q000097:blood*; D020143:Gangliosidoses, GM2 / Q000097:blood; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012799:Sialyltransferases / Q000097:blood / Q000172:deficiency; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D005679:G(M3) Ganglioside; D005732:Gangliosides; C026226:ganglioside, GD3; C019403:ganglioside, GD2; D012799:Sialyltransferases
keywords: GM3 synthase deficiency; Gangliosides; Mass spectrometry; Neurological disorders