title: Elucidation of the presence and location of t-Boc protecting groups in amines and dipeptides using on-column H/D exchange HPLC/ESI/MS.
abstract: High performance liquid chromatography/mass spectrometry (HPLC/MS) has become a widely used technique for routine analysis of pharmaceutical compounds. The constant search for new drugs requires the development of time-efficient methods that can be employed in high-throughput screening of combinatorial libraries of a variety of compounds, including amines and peptides. Conventional HPLC/MS is a powerful technique that can easily be automated and is suitable for comprehensive screening purposes. However, the unequivocal determination of the presence and location of important carbamoyl protecting groups of amines is often elusive because of their inherent instability under MS conditions. In this study, the use of on-column H/D exchange HPLC/ESI/MS for structure elucidation of t-Boc protecting groups which can often not be detected by MS because of facile McLafferty rearrangement has been examined. We demonstrate that employing a deuterated mobile phase in HPLC/MS analysis provides a convenient tool for the determination of the absence or presence of t-Boc protecting groups in amines and peptides.
authors.affiliation: Chemistry Department, Georgetown University, Washington, District of Columbia 20057, USA. cw27@georgetown.edu
authors.forename: Christian
authors.initials: C
authors.lastname: Wolf
authors.forename: Cristina N
authors.initials: CN
authors.lastname: Villalobos
authors.forename: Paul G
authors.initials: PG
authors.lastname: Cummings
authors.forename: Sonya
authors.initials: S
authors.lastname: Kennedy-Gabb
authors.forename: Mark A
authors.initials: MA
authors.lastname: Olsen
authors.forename: Gudrun
authors.initials: G
authors.lastname: Trescher
mesh_terms: D000588:Amines / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D004151:Dipeptides / Q000737:chemistry*; D007202:Indicators and Reagents; D019151:Peptide Library; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D000588:Amines; D004151:Dipeptides; D007202:Indicators and Reagents; D019151:Peptide Library