title: Quantitation of repaglinide and metabolites in mouse whole-body thin tissue sections using droplet-based liquid microjunction surface sampling-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry.
abstract: Herein, quantitation aspects of a fully automated autosampler/HPLC-MS/MS system applied for unattended droplet-based surface sampling of repaglinide dosed thin tissue sections with subsequent HPLC separation and mass spectrometric analysis of parent drug and various drug metabolites were studied. Major organs (brain, lung, liver, kidney and muscle) from whole-body thin tissue sections and corresponding organ homogenates prepared from repaglinide dosed mice were sampled by surface sampling and by bulk extraction, respectively, and analyzed by HPLC-MS/MS. A semi-quantitative agreement between data obtained by surface sampling and that by employing organ homogenate extraction was observed. Drug concentrations obtained by the two methods followed the same patterns for post-dose time points (0.25, 0.5, 1 and 2 h). Drug amounts determined in the specific tissues was typically higher when analyzing extracts from the organ homogenates. In addition, relative comparison of the levels of individual metabolites between the two analytical methods also revealed good semi-quantitative agreement.
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA.
authors.forename: Weiqi
authors.initials: W
authors.lastname: Chen
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA.
authors.forename: Lifei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA.
authors.forename: Gary J
authors.initials: GJ
authors.lastname: Van Berkel
authors.affiliation: Organic and Biological Mass Spectrometry Group, Chemical Sciences Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831, USA. Electronic address: kerteszv@ornl.gov.
authors.forename: Vilmos
authors.initials: V
authors.lastname: Kertesz
authors.affiliation: Pharmaceutical Candidate Optimization, Bristol-Myers Squibb Research and Development, Princeton, NJ 08543, USA. Electronic address: jinping.gan@bms.com.
authors.forename: Jinping
authors.initials: J
authors.lastname: Gan
mesh_terms: D000818:Animals; D002219:Carbamates / Q000032:analysis* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D007004:Hypoglycemic Agents / Q000032:analysis* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008845:Microinjections; D008867:Microtomy; D010880:Piperidines / Q000032:analysis* / Q000378:metabolism; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods; D014018:Tissue Distribution
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide
keywords: Autosampler; Droplet-based liquid extraction; Liquid microjunction; Quantitation; Repaglinide; Spatial distribution