title: Investigation of the effects of 24 bio-matrices on the LC-MS/MS analysis of morinidazole.
abstract: This study compares and evaluates the effect of various matrices on liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) analysis. Permanent post-column infusion (PCI) was used to quantify matrix effects. In this way, the suppressed or enhanced signal of the target material resulting from different co-eluting matrix components could be assessed. Twenty-four biological samples from in vivo and in vitro experiments were selected for this study. In addition, 7 sample components were further analyzed after sample preparation by protein precipitation. Multiple regression analysis was used to investigate the collinear relationship between matrix effects and co-eluted components at different time intervals. We found that salt was the dominant factor which impacted changes in signal detection. In order to eliminate it, we used ammonium formate as a modifier of the mobile phase which resulted in charge-state redistribution profiles so that a homogeneous matrix formed. By employing pulse gradient chromatography in the presence of 5mM ammonium formate, favorable improvements of enhanced signal intensity and reduced matrix effects were obtained. These experiments also indicated the feasibility of using analogue IS during bio-analysis which contributed to an overall faster assay that would be suitable for drug discovery and development purposes.
authors.affiliation: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 646 SongTao Road, Shanghai 201203, PR China. lvwenxu@hotmail.com
authors.forename: Wenxu
authors.initials: W
authors.lastname: Lv
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid; D019295:Computational Biology; D005240:Feasibility Studies; D005561:Formates / Q000737:chemistry; D006801:Humans; D016014:Linear Models; D008795:Metronidazole / Q000031:analogs & derivatives / Q000032:analysis; D051379:Mice; D009593:Nitroimidazoles / Q000032:analysis* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D000900:Anti-Bacterial Agents; D005561:Formates; D009593:Nitroimidazoles; C030544:formic acid; D008795:Metronidazole; C547405:morinidazole