Method comparison of HPLC-ninhydrin-photometry and UHPLC-PITC-tandem mass spectrometry for serum amino acid analyses in patients with complex congenital heart disease and controls

Metabolomics. 2020 Dec 15;16(12):128. doi: 10.1007/s11306-020-01741-8.

Abstract

Introduction: Metabolomics studies are not routine when quantifying amino acids (AA) in congenital heart disease (CHD).

Objectives: Comparative analysis of 24 AA in serum by traditional high-performance liquid chromatography (HPLC) based on ion exchange and ninhydrin derivatisation followed by photometry (PM) with ultra-high-performance liquid chromatography and phenylisothiocyanate derivatisation followed by tandem mass spectrometry (TMS); interpretation of findings in CHD patients and controls.

Methods: PM: Sample analysis as above (total run time, ~ 119 min). TMS: Sample analysis by AbsoluteIDQ® p180 kit assay (BIOCRATES Life Sciences AG, Innsbruck, Austria), which employs PITC derivatisation; separation of analytes on a Waters Acquity UHPLC BEH18 C18 reversed-phase column, using water and acetonitrile with 0.1% formic acid as the mobile phases; and quantification on a Triple-Stage Quadrupole tandem mass spectrometer (Thermo Fisher Scientific, Waltham, MA) with electrospray ionisation in the presence of internal standards (total run time, ~ 8 min). Calculation of coefficients of variation (CV) (for precision), intra- and interday accuracies, limits of detection (LOD), limits of quantification (LOQ), and mean concentrations.

Results: Both methods yielded acceptable results with regard to precision (CV < 10% PM, < 20% TMS), accuracies (< 10% PM, < 34% TMS), LOD, and LOQ. For both Fontan patients and controls AA concentrations differed significantly between methods, but patterns yielded overall were parallel.

Conclusion: Serum AA concentrations differ with analytical methods but both methods are suitable for AA pattern recognition. TMS is a time-saving alternative to traditional PM under physiological conditions as well as in patients with CHD.

Trial registration number: ClinicalTrials.gov Identifier NCT03886935, date of registration March 27th, 2019 (retrospectively registered).

Keywords: Amino acid metabolism; Congenital heart disease; Fontan; Metabolomics; Pattern recognition; Tandem mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / blood*
  • Biomarkers
  • Case-Control Studies
  • Chromatography, High Pressure Liquid* / methods
  • Heart Defects, Congenital / blood*
  • Heart Defects, Congenital / diagnosis*
  • Humans
  • Metabolomics / methods
  • Ninhydrin*
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry* / methods

Substances

  • Amino Acids
  • Biomarkers
  • Ninhydrin

Associated data

  • ClinicalTrials.gov/NCT03886935