title: Fused-core silica column high-performance liquid chromatography/tandem mass spectrometric determination of rimonabant in mouse plasma.
abstract: A high-performance liquid chromatography (HPLC) method using a fused-core silica particle packing was evaluated to allow fast and efficient separation for the analysis of pharmaceutical compounds. Fused-core particles are produced by "fusing" a porous silica layer onto a solid silica particle. The efficiencies of columns packed with 2.7 microm "fused-core" particles (a 0.5 microm porous shell fused to a solid 1.7 microm silica core particle) and 1.7 microm porous particles were compared in reversed-phase HPLC using rimonabant as an analyte. The fused-core silica materials providing the shorter diffusional mass transfer path for solutes are less affected in resolving power by increases in mobile-phase velocity than the sub-2 microm porous silica packings resulting in faster separations and higher sample throughput. This fast HPLC technology is comparable with ultrahigh-pressure liquid chromatography (UHPLC) in terms of chromatographic performance but demands neither expensive ultra-high-pressure instrumentation nor new laboratory protocols. The column effluent was directly connected to the atmospheric pressure chemical ionization (APCI) source prior to tandem mass spectrometric detection. In this work, the described fast HPLC-MS/MS and UHPLC-MS/MS approaches requiring approximately 1.5 min per sample were applied and compared for the determination of the rimonabant in mouse plasma samples at the low nanograms per milliliter region in support of a pharmacodynamic study.
authors.affiliation: Drug Metabolism and Pharmacokinetics Department, Schering-Plough Research Institute, Kenilworth, New Jersey 07033, USA. yunsheng.hsieh@scorp.com
authors.forename: Yunsheng
authors.initials: Y
authors.lastname: Hsieh
authors.forename: Christine J G
authors.initials: CJ
authors.lastname: Duncan
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Brisson
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D051379:Mice; D010880:Piperidines / Q000097:blood*; D011720:Pyrazoles / Q000097:blood*; D015203:Reproducibility of Results; D000077285:Rimonabant; D012680:Sensitivity and Specificity; D012822:Silicon Dioxide / Q000737:chemistry*; D053719:Tandem Mass Spectrometry / Q000379:methods; D013997:Time Factors
chemical_list: D010880:Piperidines; D011720:Pyrazoles; D012822:Silicon Dioxide; D000077285:Rimonabant