title: Investigation of diltiazem metabolism in fish using a hybrid quadrupole/orbital trap mass spectrometer.
abstract: BACKGROUND
  Diltiazem, a calcium channel blocker drug, is widespread in the environment because of its incomplete elimination during water treatment. It can cause negative effects on aquatic organisms; thus, a rapid and sensitive liquid chromatography/mass spectrometry (LC/MS) method to detect its presence was developed. Our approach is based on accurate mass measurements using a hybrid quadrupole-orbital trap mass spectrometer that was used to measure diltiazem and its metabolites in fish tissue.
  
  
  METHODS
  Blood plasma, muscle, liver, and kidney tissues of rainbow trout (Oncorhynchus mykiss), exposed for 42 days to 30 μg L(-1) diltiazem, were used for the method development. No metabolite standards were required to identify the diltiazem biotransformation products in the fish tissue.
  
  
  RESULTS
  Overall, 17 phase I diltiazem metabolites (including isomeric forms) were detected and tentatively identified using the MassFrontier spectral interpretation software. A semi-quantitative approach was used for organ-dependent comparison of the metabolite concentrations.
  
  
  CONCLUSIONS
  These data increase our understanding about diltiazem and its metabolites in aquatic organisms, such as fish. These encompass desmethylation, desacetylation and hydroxylation as well as their combinations. This study represents the first report of the complex diltiazem phase I metabolic pathways in fish.
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Koba
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Christoph
authors.initials: C
authors.lastname: Steinbach
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Hana Kocour
authors.initials: HK
authors.lastname: Kroupová
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Kateřina
authors.initials: K
authors.lastname: Grabicová
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Randák
authors.affiliation: University of South Bohemia in Ceske Budejovice, Faculty of Fisheries and Protection of Waters, South Bohemian Research Center of Aquaculture and Biodiversity of Hydrocenoses, Research Institute of Fish Culture and Hydrobiology, Zatisi 728/II, 389 25, Vodnany, Czech Republic.
authors.forename: Roman
authors.initials: R
authors.lastname: Grabic
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000737:chemistry* / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D004110:Diltiazem / Q000737:chemistry* / Q000378:metabolism*; D005399:Fishes / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D009132:Muscles / Q000737:chemistry / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D014874:Water Pollutants, Chemical; D004110:Diltiazem