title: A rapid ultra performance liquid chromatography tandem mass spectrometric method for measuring amino acids associated with maple syrup urine disease, tyrosinaemia and phenylketonuria.
abstract: 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) 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Waters Corporation, Milford, MA, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Freeto
authors.forename: Donald
authors.initials: D
authors.lastname: Mason
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
authors.forename: Robert H
authors.initials: RH
authors.lastname: Scott
authors.forename: Srinivas B
authors.initials: SB
authors.lastname: Narayan
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bennett
mesh_terms: D000596:Amino Acids / Q000097:blood*; D001774:Blood Chemical Analysis / Q000379:methods; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002852:Chromatography, Ion Exchange / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D008375:Maple Syrup Urine Disease / Q000097:blood / Q000175:diagnosis*; D009555:Ninhydrin / Q000737:chemistry; D010661:Phenylketonurias / Q000097:blood / Q000175:diagnosis*; D012015:Reference Standards; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors; D020176:Tyrosinemias / Q000097:blood / Q000175:diagnosis*
chemical_list: D000596:Amino Acids; D009555:Ninhydrin