Influence of pre-analytical conditions on the interpretation of zopiclone concentrations in whole blood

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 10 mg Imovane®. Aliquots of 1 g 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.