Abstract
BACKGROUND: Lysosphingolipids (LysoSLs) are derivatives of sphingolipids which have lost the amide-linked acyl chain. More recently, LysoSLs have been identified as storage compounds in several sphingolipidoses, including Gaucher, Fabry and Niemann-Pick diseases. To date, different methods have been developed to measure each individual lysosphingolipid in plasma. This report describes a rapid liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) assay for simultaneous quantification of several LysoSLs in plasma.
METHODS: We analyzed the following compounds: hexosylsphingosine (HexSph), globotriaosylsphingosine (LysoGb3), lysosphingomyelin (LysoSM) and lysosphingomyelin-509 (LysoSM-509). The sample preparation requires only 100 μL of plasma and consists of an extraction with a mixture of MeOH/acetone/H2O (45:45:10, v/v).
RESULTS: The method validation showed high sensitivity, an excellent accuracy and precision. Reference ranges were determined in healthy adult and pediatric population. The results demonstrate that the LC-MS/MS method can quantify different LysoSLs and can be used to identify patients with Fabry (LysoGb3), Gaucher and Krabbe (HexSph) diseases, prosaposine deficiency (LysoGb3 and HexSph), and Niemann-Pick disease types A/B and C (LysoSM and LysoSM-509).
CONCLUSIONS: This LC-MS/MS method allows a rapid and simultaneous quantification of LysoSLs and is useful as a biochemical diagnostic tool for sphingolipidoses.
Original language | English |
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Pages (from-to) | 403-414 |
Number of pages | 12 |
Journal | Clinical Chemistry and Laboratory Medicine |
Volume | 55 |
Issue number | 3 |
DOIs | |
Publication status | Published - Aug 17 2016 |
Keywords
- Adolescent
- Adult
- Aged
- Biomarkers
- Case-Control Studies
- Child
- Child, Preschool
- Chromatography, Liquid
- Humans
- Infant
- Infant, Newborn
- Middle Aged
- Reference Values
- Reproducibility of Results
- Sphingolipidoses
- Sphingolipids
- Tandem Mass Spectrometry
- Young Adult
- Comparative Study
- Journal Article