Zopiclone concentrations in oral fluid and blood after, administration of therapeutic doses of zopiclone

• Published in: Forensic science international 2017-09, Vol.278, p.177-183
• Main Authors: Hjelmeland, Knut, Gustavsen, Ingebjørg, Øiestad, Elisabeth Leere, Øiestad, Åse Marit Leere, Høiseth, Gudrun, Mørland, Jørg
• Format: Article
• Language: English
• Subjects: Alcohol; Blood; Blood levels; Chromatography; Correlation analysis; Detection time; Dilution; Drug dosages; Drunk driving; Forensic sciences; Intercept oral fluid collection device; Ions; Mass spectrometry; Methamphetamine; Oral fluid; Oral fluid to whole blood ratio; Saliva; Scientific imaging; Urine; Zopiclone
• ISSN: 0379-0738; 1872-6283
• DOI: 10.1016/j.forsciint.2017.07.004

•Oral fluid zopiclone concentration is unsuitable to estimate blood concentration.•Intake of a meal reduces the oral fluid to blood concentration ratio.•Intake of 10mg zopiclone can be detected in oral fluid up to 14 days. Little is known about the relationship between concentrations in oral fluid (OF) and blood for the widely prescribed hypnotic drug zopiclone. The purpose of this study was to investigate the usefulness of OF zopiclone concentrations to predict blood zopiclone concentrations in order to introduce OF testing as an alternative to more cumbersome blood testing. 16 healthy young male volunteers received capsules of either 5 or 10mg zopiclone on two different study days separated by at least one week. Blood and OF were collected simultaneously at baseline and 9 times after intake of zopiclone on each study day. In addition an OF sample was collected 24–81h after intake. Lunch was served between samples taken 2.5 and 3.5h after intake. All samples were analysed for zopiclone, and the cut-off was 10ng/ml in blood and 0.2ng/ml in OF–buffer mixture. Zopiclone was detected in all OF samples during the study day. After 24–81h, all subjects were also positive for zopiclone in OF, except from three subjects ingesting the 5mg dose. In a single case zopiclone was detected in a baseline OF sample 14days after intake on an earlier study day. Zopiclone was detected in both OF and blood in 231 OF/blood pairs, and a significant but weak correlation between OF and blood concentration was seen (R2 of 0.30). The median (range) zopiclone OF/blood concentration ratio (ZOBCR) for all samples were 3.3 (0.8–18). The ZOBCR decreased when the OF volume increased. After 30 of 31 given doses of zopiclone, the ZOBCR was higher in samples collected before lunch than samples collected after lunch. Vast intra- and interindividual differences in ZOBCR were found, and the correlation between OF and blood concentration was less pronounced than reported in former studies. In accordance with earlier studies we found a negative correlation between ZOBCR and OF volume. The ZOBCR decreases in relation to recent intake of a meal, probably because stimulated saliva production causes “dilution” of saliva. OF zopiclone concentration appeared unsuitable for estimation of blood zopiclone concentration. Due to long detection time, analysis of zopiclone in OF might be useful to detect non-recent, previous intake.