UPLC-MS/MS analysis of C5-acylcarnitines in dried blood spots

Clin Chim Acta. 2013 Jun 5:421:41-5. doi: 10.1016/j.cca.2013.03.001. Epub 2013 Mar 13.

Abstract

Background: Metabolic screening including newborn screening requires further differentiation of C5-acylcarnitines in order to separate different metabolic disorders and to detect interferents like pivalic acid originating from antibiotics.

Methods: For individual quantification of C5-acylcarnitine isoforms in dried blood spots we combined UPLC using a C18 column and gradient elution with tandem mass spectrometry in ESI+mode.

Results: Results were linear, coefficients of determination (R(2))>0.9977, intra- and inter-assay coefficients of variations <5.2%, recovery 96.8-105.2%, limits of detection and quantitation <0.2 μmol/L. Out of 29.309 blood samples of the isolated population of the Faroe Islands 56 exceeded the cut-off of 0.5 μmol/L for C5-acylcarnitine; 45 of which could be retested using the method described. Pivaloylcarnitine was identified in 43 samples, isovalerylcarnitine was found in two samples.

Conclusions: The method was developed to allow direct re-analysis of samples showing elevated concentrations of C5-acylcarnitines in a metabolic screening program based on quantification of acylcarnitines after butylation. The technique should be especially useful in newborn screening for exclusion of false positives and for differentiation between isovaleric acidemia and 2-methylbutyryl-CoA dehydrogenase deficiency.

MeSH terms

  • Amino Acid Metabolism, Inborn Errors / blood
  • Amino Acid Metabolism, Inborn Errors / diagnosis*
  • Carnitine / analogs & derivatives*
  • Carnitine / blood
  • Chromatography, High Pressure Liquid / methods
  • Diagnosis, Differential
  • Dried Blood Spot Testing
  • Humans
  • Infant, Newborn
  • Isovaleryl-CoA Dehydrogenase / blood
  • Isovaleryl-CoA Dehydrogenase / deficiency*
  • Limit of Detection
  • Neonatal Screening
  • Reproducibility of Results
  • Tandem Mass Spectrometry

Substances

  • acylcarnitine
  • 3-methylbutyrylcarnitine
  • pivaloylcarnitine
  • Isovaleryl-CoA Dehydrogenase
  • Carnitine

Supplementary concepts

  • 2-Methylbutyryl-CoA Dehydrogenase Deficiency
  • Acidemia, isovaleric