title: Bioconcentration of two basic pharmaceuticals, verapamil and clozapine, in fish.
abstract: The present study examined the bioconcentration of 2 basic pharmaceuticals: verapamil (a calcium channel blocker) and clozapine (an antipsychotic compound) in 2 fresh water fishes, fathead minnow and channel catfish. In 4 separate bioconcentration factor (BCF) experiments (2 chemicals × 1 exposure concentration × 2 fishes), fathead minnow and channel catfish were exposed to 190 μg/L and 419 μg/L of verapamil (500 μg/L nominal) or 28.5 μg/L and 40 μg/L of clozapine (50 μg/L nominal), respectively. Bioconcentration factor experiments with fathead consisted of 28 d uptake and 14 d depuration, whereas tests conducted on catfish involved a minimized test design, with 7 d each of uptake and depuration. Fish (n = 4-5) were sampled during exposure and depuration to collect different tissues: muscle, liver, gills, kidneys, heart (verapamil tests only), brain (clozapine tests only), and blood plasma (catfish tests only). Verapamil and clozapine concentrations in various tissues of fathead and catfish were analyzed using liquid chromatography-mass spectrometry. In general, higher accumulation rates of the test compounds were observed in tissues with higher perfusion rates. Accumulation was also high in tissues relevant to pharmacological targets in mammals (i.e. heart in verapamil test and brain in the clozapine test). Tissue-specific BCFs (wet wt basis) for verapamil and clozapine ranged from 0.7 to 75 and from 31 to 1226, respectively. Tissue-specific concentration data were used to examine tissue-blood partition coefficients.
authors.affiliation: Institute of Applied Sciences, Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
authors.forename: Gopinath C
authors.initials: GC
authors.lastname: Nallani
authors.affiliation: Institute of Applied Sciences, Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
authors.forename: Regina E
authors.initials: RE
authors.lastname: Edziyie
authors.affiliation: Institute of Applied Sciences, Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Paulos
authors.affiliation: Institute of Applied Sciences, Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
authors.forename: Barney J
authors.initials: BJ
authors.lastname: Venables
authors.affiliation: Pfizer Global Research and Development, Groton, Connecticut, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Constantine
authors.affiliation: Institute of Applied Sciences, Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
authors.forename: Duane B
authors.initials: DB
authors.lastname: Huggett
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003024:Clozapine / Q000032:analysis* / Q000302:isolation & purification; D003530:Cyprinidae / Q000378:metabolism*; D005260:Female; D005880:Gills / Q000737:chemistry / Q000378:metabolism; D007059:Ictaluridae / Q000378:metabolism*; D007668:Kidney / Q000737:chemistry / Q000378:metabolism; D059625:Liquid-Liquid Extraction; D008099:Liver / Q000737:chemistry / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D009132:Muscles / Q000737:chemistry / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism; D014700:Verapamil / Q000032:analysis* / Q000302:isolation & purification; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000302:isolation & purification
chemical_list: D014874:Water Pollutants, Chemical; D014700:Verapamil; D003024:Clozapine
keywords: Bioconcentration; Bioconcentration factor (BCF); Channel catfish; Fathead minnow; Pharmaceuticals