Open AccessA rapid ultra performance liquid chromatography tandem mass spectrometric method for measuring amino acids associated with maple syrup urine disease, tyrosinaemia and phenylketonuria
Author(s) -
Scott M. Freeto,
Donald S. Mason,
Jie Chang,
Robert H Scott,
Srinivas B. Narayan,
Michael J. Bennett
Publication year - 2007
Publication title -
annals of clinical biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.6
H-Index - 80
eISSN - 1758-1001
pISSN - 0004-5632
DOI - 10.1258/000456307781646012
Subject(s) - maple syrup urine disease , chromatography , chemistry , ninhydrin , high performance liquid chromatography , amino acid , tandem mass spectrometry , derivatization , ion chromatography , mass spectrometry , urine , leucine , biochemistry
Background: Patients with inherited disorders of amino acid metabolism including maple syrup urine disease, tyrosinaemia and phenylketonuria on dietary management require frequent monitoring of disease-relevant plasma amino acids in order to optimize therapeutic benefit. Poorly controlled maple syrup urine disease in particular may result in catastrophic metabolic decompensation. Most methods for monitoring amino acid concentrations are time-consuming and have clinically impractical turnaround times, particularly when the required time to run standards and control samples is taken into account. Methods: We have analysed plasma amino acids using standard ion-exchange chromatography with ninhydrin detection in an amino acid analyser and compared the data with that obtained for the same samples using ultra-performance liquid chromatography (UPLC TM ) separation with detection by tandem mass spectrometry. Results: The two methodologies compared very well for the measurement of six important amino acids with correlation coefficients greater than 0.96 for all. The time for sample preparation was longer for the UPLC methodology as batched derivatization and evaporation is required but UPLC-tandem mass spectrometry generated sample results every 8 min while conventional ion-exchange chromatography took almost 1 h per sample. Conclusion: UPLC-tandem mass spectrometry generates data that compares well with existing 'gold standard' methodologies but significantly reduces sample turnaround time. Decreasing the turnaround time for amino acid analyses is very likely to improve clinical care for patients with amino acid disorders as dietary adjustments can be made sooner.