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Purpose: The risk of traffic accident involvement is increased among patients prescribed the z-hypnotic drug zopiclone. Clinical test observations able to indicate drug impairment are therefore essential. This study compared the findings of a simplified clinical test of impairment (SCTI) with those of a battery of computerized psychomotor tests of impairment (CPTI)., Methods: 16 healthy young male volunteers attended a research unit on four different study days, receiving in randomized order either placebo, zopiclone 5mg, zopiclone 10mg, or alcohol 50g. The SCTI was performed twice and the CPTI was performed three times on each study day, with blood samples being collected for drug analysis., Results: The SCTI (and the CPTI) was able to demonstrate impairment at 1.5h, but no major impairment was found at 7h with the SCTI, after intake of both zopiclone and ethanol. The CPTI detected a significantly higher proportion of impaired observations than the SCTI, both for zopiclone and for ethanol, at all concentration levels. The sensitivity of the clinical tests in detecting blood drug concentrations often associated with impairment, due to zopiclone (above 23ng/ml) and alcohol (above 0.5g/l), was low, revealing 27 per cent and 18 per cent, respectively. The specificity, however, was higher, both for zopiclone (88 per cent) and for alcohol (96 per cent)., Discussion: The SCTI may be a useful tool, especially during roadside investigation, when the police are in doubt as to whether the apprehended driver is impaired or not. A subject, who has consumed zopiclone or alcohol, tested with the SCTI, with one or more subtests diverging from a habitual result, is likely to have a blood zopiclone concentration above 23ng/ml or a BAC above 0.5g/l. A negative result, however, is less helpful., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The concentrations of zolpidem and zopiclone were determined in peripheral blood samples in two forensic materials collected over a 10-year period (2001-2010). The z-hypnotics were determined in venous blood from living subjects (impaired drivers) and in femoral blood from deceased persons (forensic autopsies), with the latter classified as intoxication or other causes of death. The z-hypnotics were determined in blood by capillary column gas chromatography (GC) with a nitrogen-phosphorous (N-P) detector after solvent extraction with n-butyl acetate. The analytical limit of quantitation (LOQ) was 0.02 mg/L for zopiclone and 0.05 mg/L for zolpidem and these have remained unchanged throughout the study. When death was attributed to drug intoxication (N=918), the median concentration of zopiclone in blood was 0.20 mg/L compared with 0.06 mg/L for other causes of death (N=1215) and 0.07 mg/L in traffic offenders (N=691) (p<0.001). Likewise, a higher median concentration (0.30 mg/L) was found in intoxication deaths involving zolpidem (N=357) compared with 0.13 mg/L for other causes of death (N=397) or 0.19 mg/L in impaired drivers (N=837) (p<0.001). Median concentration in blood of both z-hypnotics were appreciably higher in intoxication deaths when no other substances were identified; 0 70 mg/L (N=12) for zopiclone and 1.35 mg/L (N=12) for zolpidem. The median concentrations of z-hypnotics in blood decreased as the number of co-ingested substances increased for intoxication deaths but not other causes of death. The most prevalent co-ingested substances were ethanol in autopsy cases and diazepam in the motorists. This large compilation of forensic cases should prove useful when toxicologists are required to interpret concentrations of z-hypnotics in blood samples in relation to cause of death., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Zopiclone is a short-acting hypnotic drug used for treatment of insomnia and its stability has been described in some detail. However, data especially on short-term pre-analytical stability is missing. This study investigated zopiclone stability differences between spiked and authentic whole blood from subjects dosed with zopiclone. In this way influence from physiological factors such as drug interactions, matrix composition and plasma protein levels were minimized. Nine volunteers participated in the study. Whole blood was obtained before and after oral administration of 10mg Imovane(®). Aliquots of 1g of authentic and spiked blood were after initial measuring, stored at 20°C during 5 days, 5 or -20°C during 3 months, and zopiclone was measured by gas chromatography with nitrogen phosphorus detection. The results showed no stability differences between authentic and spiked blood but confirmed the very short stability in whole blood at ambient temperature. In summary, the stability was less than 1 day at 20°C, less than 2 weeks at 5°C but stable for 3 months at -20°C. This study demonstrates the importance of controlling pre-analytical conditions from sampling to analysis to avoid misinterpretation of toxicological results., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Zopiclone is a common drug in forensic cases and it is frequently analyzed in biological materials using different analytical methods. Zopiclone is unstable in certain solvents and depending on storage conditions unstable in biological fluids; however its stability in human whole blood has not yet been established in detail. Therefore, the following investigation was performed to study the stability of zopiclone in both spiked and authentic human blood. First, spiked blood samples were stored at -20 degrees C, 5 degrees C and 20 degrees C and the degradation of zopiclone was investigated. Second, authentic and spiked blood samples were stored at 5 degrees C and differences in zopiclone stability were studied. Third, processed sample stability and effect of freeze/thaw cycles were evaluated. Analyses were performed by GC-NPD and zopiclone concentrations were measured at selected time intervals. The study showed that zopiclone degrades in human blood depending on time and temperature and may not be detected after long-term storage. 2-amino-5-chloropyridine was identified as the primary degradation product from zopiclone. At refrigerator temperature zopiclone was stable less than 1 month in both spiked and authentic human blood samples. The best storage condition was at -20 degrees C even at short storage times, as freeze-thaw had no influence on the results. In butyl acetate extracts, zopiclone was stable at least 2 days when kept in the autosampler at ambient temperature. We conclude that preanalytical factors have great impact on analytical results and should be addressed when interpreting whole blood zopiclone concentrations., ((c) 2010 Elsevier Ireland Ltd. All rights reserved.)