title: Acquired and congenital fast albumin bands; insights from electrospray TOF analysis of whole plasma into drug binding and albumin recycling.
abstract: OBJECTIVE
  To define the underlying cause of unusual fast albumin bands detected on plasma protein electrophoresis of two patients.
  
  
  METHODS
  Plasma was examined by electrospray time-of-flight mass spectrometry (TOF MS) to assess the possibility of congenital or acquired structural modifications.
  
  
  RESULTS
  In one patient whole protein MS indicated a drop of 486Da in the mass of 5.1% of the albumin molecules. This and the presence of an additional minor product (65,806Da) lacking a C-terminal phenylalanine (-147Da) indicated that this was albumin Rugby Park; an electrophoretically fast albumin variant caused by a splice site mutation (GT>CT) in intron 13 of the albumin gene. The second patient had an acquired alteration with a drift of albumin mobility to the anode. This severely ill patient was on intra venous antibiotics and electrospray TOF MS showed a stuttered repetition of the 66,439/66,558Da albumin isoforms at multiples of 455-459Da corresponding to the covalent attachment of 1, 2, 3 and 4 molecules of flucloxacillin. This modification of +455Da was also detected in a control on a 1g/day oral dose of flucloxacillin.
  
  
  CONCLUSIONS
  Both aberrations were associated with diminished albumin concentrations. The C-terminal truncation of Rugby Park (albumin, 29g/l) likely interferes with receptor binding and albumin scavenging, while the 20g/l albumin in the second patient was mostly due to renal disease. In both cases electrospray TOF MS proved a rapid (5min) sensitive (0.2μl plasma) and highly informative way of analysing whole plasma or serum.
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand; University of Otago, Christchurch School of Medicine, Christchurch, New Zealand. Electronic address: steve.brennan@otago.ac.nz.
authors.forename: Stephen O
authors.initials: SO
authors.lastname: Brennan
authors.affiliation: Canterbury Health Laboratories, Christchurch, New Zealand.
authors.forename: Richard
authors.initials: R
authors.lastname: Mackay
mesh_terms: D006801:Humans; D007438:Introns; D008297:Male; D008875:Middle Aged; D009154:Mutation; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010949:Plasma; D011485:Protein Binding; D012709:Serum Albumin / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D004364:Pharmaceutical Preparations; D012709:Serum Albumin
keywords: Acquired and genetic modifications; Albumin; Albumin recycling; Electrophoresis; Flucloxacillin; Serum mass spectrometry