title: Characterization and performance of MALDI on a triple quadrupole mass spectrometer for analysis and quantification of small molecules.
abstract: The usefulness of MALDI for small-molecule work has been limited by matrix chemical interference in the mass range of interest, tedious sample preparation, and various crystallization and sample deposition issues. We report instrument characterization and small-molecule quantification performance data from a high repetition rate laser MALDI ion source coupled to a triple quadrupole mass spectrometer. The high repetition rate laser improves sensitivity and precision and allows a proportional increase in sample throughput. Tandem mass spectrometry is used to discriminate the signal from the high chemical background caused by the MALDI matrix. Successful quantification requires use of an internal standard and a means of sample cleanup for typical in vitro sample compositions. This instrument combination and analysis technique is relatively insensitive to sample crystal quality and spot homogeneity. Quantitative performance results are characterized for 53 small-molecule pharmaceutical compounds and compared to those obtained by ESI-MS/MS. Further comparison between MALDI and ESI is examined, and the potential for high-throughput MALDI-MS/MS quantification is demonstrated.
authors.affiliation: Groton/New London Laboratories, Pfizer Global Research and Development, Eastern Point Road, Groton, Connecticut 06340, USA. Jason.s.govey@pfizer.com
authors.forename: Jason
authors.initials: J
authors.lastname: Gobey
authors.forename: Mark
authors.initials: M
authors.lastname: Cole
authors.forename: John
authors.initials: J
authors.lastname: Janiszewski
authors.forename: Thomas
authors.initials: T
authors.lastname: Covey
authors.forename: Tung
authors.initials: T
authors.lastname: Chau
authors.forename: Peter
authors.initials: P
authors.lastname: Kovarik
authors.forename: Jay
authors.initials: J
authors.lastname: Corr
mesh_terms: D003373:Coumaric Acids / Q000737:chemistry; D003460:Crystallization; D006801:Humans; D008861:Microsomes / Q000737:chemistry / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry
chemical_list: D003373:Coumaric Acids; C007175:alpha-cyano-4-hydroxycinnamate