ABSTRACT
Data from previous experimental studies on the detection time of oxazepam and zopiclone in biological matrices are limited. The aim of this study was to examine the detection time in urine and oral fluid after single oral doses of oxazepam and zopiclone. Ten healthy volunteers received 25 mg of oxazepam in the evening of Day 1 and 7.5 mg of zopiclone in the evening of Day 3. Urine and oral fluid samples were collected twice daily for 9 days, with an additional sampling the day after ingestion of zopiclone. A total of 19 samples of both urine and oral fluid from each participant were analyzed using fully validated chromatographic methods. The median detection time for oxazepam was 91 h (range 73-108) in urine and 67 h (range 50-98) in oral fluid. The median detection time for zopiclone in urine was 49 h (range 25-98) and 59 h (range 48-146) in oral fluid. The metabolite zopiclone N-oxide showed a detection time of 36 h (range 25-84) in urine. The area under the concentration-time curve (AUCTotal) in urine corrected for creatinine was 150 µmol/L/mmol/L*h (range 105-216) for oxazepam and 1.60 µmol/L/mmol/L*h (range 0.79-4.53) for zopiclone. In oral fluid, the AUCtotal was 673 nmol/L*h (range 339-1,316) for oxazepam and 2,150 nmol/L*h (range 493-4,240) for zopiclone. In conclusion, oxazepam can be detected longer in urine than in oral fluid, while zopiclone can be detected longer in oral fluid than in urine. The high AUCTotal for zopiclone in oral fluid shows that the transfer into oral fluid is significant. In certain individuals the detection time of zopiclone in oral fluid is long. These results can be helpful when interpreting drug testing analyzes.
Subject(s)
Azabicyclo Compounds/urine , Models, Theoretical , Oxazepam/urine , Piperazines/urine , Saliva/chemistry , Substance Abuse Detection/methods , Adolescent , Adult , Area Under Curve , Azabicyclo Compounds/administration & dosage , Azabicyclo Compounds/analysis , Drug Administration Schedule , Female , Healthy Volunteers , Humans , Limit of Detection , Male , Oxazepam/administration & dosage , Oxazepam/analysis , Piperazines/administration & dosage , Piperazines/analysis , Substance Abuse Detection/standards , Time Factors , Young AdultABSTRACT
Benzodiazepines are commonly seen in samples submitted for drug testing of patients, people involved in child welfare cases, work-place drug testing, as well as in drug-facilitated assaults. Limited previous experimental studies are available regarding the excretion of benzodiazepines in urine and oral fluid. The aim of this study was to investigate the concentrations of diazepam and alprazolam in oral fluid and urine for up to 2 weeks after ingestion of a single oral dose in healthy volunteers. A total of 11 healthy volunteers ingested 10 mg diazepam at the start of the study and 0.5 mg alprazolam on Day 3 of the study. A total number of 10 oral fluid samples and 17 urine samples were collected from each participant. The samples were analyzed by liquid chromatography with tandem mass spectroscopy and ultra-high performance liquid chromatography tandem mass spectrometry methods. The median detection time was 252 h for the longest detected diazepam metabolite in urine (oxazepam, range 203-322) and 132 h in oral fluid (N-desmethyldiazepam, range 109-136). For alprazolam, the median detection time was 36 h (metabolite α-OH-alprazolam, range 26-61) in urine and 26 h (alprazolam, range 4-37) in oral fluid. These results show that detection times are only 36 h for alprazolam in urine after intake of a single therapeutic oral dose. For diazepam in urine, detection times were 11 days. Detection times were generally shorter in oral fluid compared to urine. The results could be helpful in the interpretation of diazepam or alprazolam findings in drug testing cases involving urine or oral fluid.
