Evaluation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Analysis of Glucosylceramide and Galactosylceramide Isoforms in Cerebrospinal Fluid of Parkinson's Disease Patients.

Autor:	Castillo-Ribelles L; Clinical Biochemistry Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain.; Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT) Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain.; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain., Arranz-Amo JA; Clinical Biochemistry Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain.; Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT) Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain., Hernández-Vara J; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain.; Neurology Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain., Samaniego-Toro D; Neurology Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain., Enriquez-Calzada S; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain., Pozo SL; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain.; Neurology Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain.; Department of Clinical and Movement Neurosciences, University College London Queen Square Institute of Neurology, London WC1N 3BG, U.K., Camprodon-Gomez M; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain.; Unit of Hereditary Metabolic Disorders, Internal Medicine Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain., Laguna A; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain.; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain., Gonzalo MA; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain.; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain., Ferrer R; Clinical Biochemistry Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain.; Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT) Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain.; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain., Martinez-Vicente M; Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Bellaterra, Barcelona 08193, Spain.; Neurodegenerative Diseases Research Group- Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED), Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain., Carnicer-Caceres C; Clinical Biochemistry Department, Vall d'Hebron University Hospital, Barcelona 08035, Spain.; Clinical Biochemistry, Drug Delivery & Therapy (CB-DDT) Research Group, Vall d'Hebron Research Institute (VHIR), Vall d'Hebron Barcelona Hospital Campus, Barcelona 08035, Spain.
Jazyk:	angličtina
Zdroj:	Analytical chemistry [Anal Chem] 2024 Aug 06; Vol. 96 (31), pp. 12875-12882. Date of Electronic Publication: 2024 Jul 24.
DOI:	10.1021/acs.analchem.4c02654
Abstrakt:	Mutations in GBA1, encoding glucocerebrosidase beta 1 (GCase), are the most common genetic risk factor for Parkinson's disease (PD). GCase dysfunction leads to an accumulation of glucosylceramide (GluCer) substrates in different organs and fluids. Despite the challenges in quantifying GluCer isoforms in biological samples, their potential clinical interest as PD biomarkers justifies the development of robust assays. An extensively evaluated high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method for quantifying 14 GluCer and galactosylceramide (GalCer) isoforms in human cerebrospinal fluid (CSF) samples is presented. Sample pretreatment, HPLC, and MS/MS parameters were optimized. Evaluation was performed according to the recommendations of the Clinical and Laboratory Standards Institute and European Medicines Agency guidelines. Four 7-point calibration curves were generated, with a linearity interval from 2.5 to 200 nM ( R 2 ≥ 0.995). The limit of quantification was set at 5 nM. Between-run precision and accuracy were up to 12.5 and 9%, respectively. After method validation, we measured the levels of GluCer and GalCer isoforms in CSF human samples, including 6 healthy controls (HC), 22 idiopathic GBA1 wild-type PD (iPD) patients, and 5 GBA1-associated PD (PD-GBA) patients. GluCer/GalCer median ratios were found to be higher in the CSF of PD-GBA patients, particularly in severe GBA1 mutations, than those in iPD and HC. The observed trends in GluCer/GalCer ratios among groups provide novel information for the comprehensive analysis of sphingolipids as potential biomarkers of PD.
Databáze:	MEDLINE
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