LC-MS/MS assays to quantify sulfatides and lysosulfatide in cerebrospinal fluid of metachromatic leukodystrophy patients

Bioanalysis. 2020 Nov;12(22):1621-1633. doi: 10.4155/bio-2020-0200. Epub 2020 Nov 5.

Abstract

Aim: Two separate LC-MS/MS assays were developed to quantitate sulfatides and lysosulfatide in human cerebrospinal fluid (CSF). Materials & methods: Lysosulfatide and the 15 most abundant sulfatide species were quantitated by LC-MS/MS using artificial CSF as surrogate matrix to prepare calibration curves. Results: Validation criteria were met (linear range: 0.02-1.00 μg/ml sulfatides [0.02-1.00 ng/ml lysosulfatide]); accuracy/precision were within ±15%. CSF from 21 children with metachromatic leukodystrophy had significantly higher sulfatide and lysosulfatide concentrations than CSF from 60 healthy children (p < 0.0001). Worse motor function correlated with higher CSF sulfatide (p = 0.0087) and lysosulfatide (p = 0.0034) levels. Conclusion: These assays, validated in patients with metachromatic leukodystrophy, may aid the clinical assessment of therapeutic responses.

Keywords: LC–MS; assay; biomarkers; clinical; method development; validation.

MeSH terms

  • Cerebrospinal Fluid / cytology
  • Cerebrospinal Fluid / metabolism*
  • Child
  • Chromatography, Liquid / methods*
  • Humans
  • Leukodystrophy, Metachromatic / diagnostic imaging*
  • Psychosine / analogs & derivatives*
  • Psychosine / metabolism
  • Sulfoglycosphingolipids / metabolism*
  • Tandem Mass Spectrometry / methods*

Substances

  • Sulfoglycosphingolipids
  • Psychosine
  • psychosine-3'-sulfate ester