title: Detection of Nitrobenzodiazepines and Their 7-Amino Metabolites in Oral Fluid.
abstract: Clonazepam, nitrazepam and flunitrazepam are frequently used benzodiazepines, both as prescribed medication and as drugs of abuse. Little is, however, known about how these drugs are excreted in oral fluid. It has been claimed that the parent drugs are more likely to be detected in oral fluid than the 7-amino metabolites. The aim of this study was to investigate whether the parent drugs or the 7-amino metabolites of the nitrobenzodiazepines were most frequently detected in authentic oral fluid samples. Oral fluid samples were collected from patients undergoing opioid maintenance treatment. Cases where clonazepam, nitrazepam, flunitrazepam and/or their metabolites were detected were included. The samples were collected using the Intercept Oral Specimen Collection Device. A cutoff concentration of 1 nM (∼0.3 ng/mL) in oral fluid-buffer mixture was applied for all the substances. A total of 1,001 oral fluid samples were positive for clonazepam and/or 7-aminoclonazepam; both substances were detected in 707 samples, only the parent drug in 64 cases and only the metabolite in 230 cases. For nitrazepam, both substances were detected in 139 samples; only the parent drug in 16 cases and only the metabolite in 56 cases. Flunitrazepam only was not detected in any sample; both substances were detected in one of these cases, and only the metabolite in three cases. This study revealed that 7-amino metabolites were more likely to be detected in oral fluid than the parent drugs.
authors.affiliation: Division of Forensic Sciences, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403 Oslo, Norway Norwegian Centre for Addiction Research (SERAF), University of Oslo, PO Box 1039, Blindern, NO-0315 Oslo, Norway vigdis.vindenes@fhi.no.
authors.forename: Vigdis
authors.initials: V
authors.lastname: Vindenes
authors.affiliation: Division of Forensic Sciences, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Dag Helge
authors.initials: DH
authors.lastname: Strand
authors.affiliation: Division of Forensic Sciences, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Paul
authors.initials: P
authors.lastname: Koksæter
authors.affiliation: Division of Forensic Sciences, Norwegian Institute of Public Health, PO Box 4404 Nydalen, NO-0403 Oslo, Norway.
authors.forename: Hallvard
authors.initials: H
authors.lastname: Gjerde
mesh_terms: D001569:Benzodiazepines / Q000032:analysis* / Q000378:metabolism; D002998:Clonazepam / Q000031:analogs & derivatives / Q000032:analysis; D005445:Flunitrazepam / Q000032:analysis; D006801:Humans; D009567:Nitrazepam / Q000032:analysis; D058850:Opiate Substitution Treatment; D012463:Saliva / Q000737:chemistry*; D015813:Substance Abuse Detection / Q000379:methods; D053719:Tandem Mass Spectrometry
chemical_list: D001569:Benzodiazepines; C020860:7-aminoclonazepam; D002998:Clonazepam; D005445:Flunitrazepam; D009567:Nitrazepam