title: A screening UHPLC-MS/MS method for the analysis of amyloid peptides in cerebrospinal fluid of preclinical species.
abstract: BACKGROUND
  Amyloid peptides are established biomarkers for Alzheimer's disease but their analysis presents major challenges.
  
  
  RESULTS
  In this article, we describe the use of ultra high-performance LC and API4000 triple quadrupole instrumentation for the quantification of amyloid peptides (Aβ(1-38) and Aβ(1-42)) in cerebrospinal fluid (CSF), using electrospray ionization with negative ion multiple reaction monitoring transitions. Sample preparation was simplified by the addition of acetonitrile and ammonium hydroxide. Although excellent sensitivity and precision was demonstrated, we observed differences in matrix suppression effects when using artificial CSF versus canine CSF for calibration curves and quality control samples.
  
  
  CONCLUSIONS
  A case study shows that the method can be used to determine the relative levels of two key peptides (Aβ(1-38) and Aβ(1-42)) compared with their predose values (a screening assay) in support of preclinical studies.
authors.affiliation: Bioanalysis Department, Janssen Research & Development, Division of Janssen Pharmaceutica N.V., Turnhoutseweg 30, 2340 Beerse, Belgium. ldillen@its.jnj.com
authors.forename: Lieve
authors.initials: L
authors.lastname: Dillen
authors.forename: Willy
authors.initials: W
authors.lastname: Cools
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Vereyken
authors.forename: Philip
authors.initials: P
authors.lastname: Timmerman
mesh_terms: D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000175:diagnosis; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D002417:Cattle; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D023421:Models, Animal; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D010446:Peptide Fragments; C078639:amyloid beta-protein (1-38); C075222:amyloid beta-protein (1-42)