{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T06:50:24Z","timestamp":1782370224051,"version":"3.54.5"},"reference-count":16,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,6,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Zopiclone (ZOP) is a sedative-hypnotic drug that is featured commonly in impaired driving, drug-facilitated crimes, accidental overdose, or suicidal intoxications. Further understanding of its blood pharmacokinetics would support its interpretation in forensic toxicology casework. This study characterizes the concentration-time pharmacokinetic profiles of ZOP and its metabolite N-desmethylzopiclone (N-DMZOP) in blood following controlled administration and evaluates the use of metabolite-to-parent ratios in estimating time of last ZOP intake. Sixteen subjects received a single oral dose of either 5\u2009mg or 10\u2009mg Imovane\u00ae, and blood samples were collected pre-dosing, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 7, 8, 9, 10, 24, and 48 hours post-dose. A paired plasma sample was also provided at the 2-hour time point. A previously validated LC\u2013MS\/MS method was used to quantify ZOP, N-DMZOP, and the degradation product 2-amino-5-chloropyridine (ACP). The aggregate regression model developed from this younger subject population was applied to independently dosed subjects and a separate group of elderly patients to determine the validity of this model in an older cohort of differing pharmacokinetic characteristics. Comparison between the 5\u2009mg and 10\u2009mg dosing groups supported a linear dose-concentration relationship. While the ratio of N-DMZOP\/ZOP can be a predictive indicator for time of ZOP intake, inter-individual differences in ZOP disposition may influence such predictions. Furthermore, age-related pharmacokinetic changes may contribute to a general underestimation of predicted time with the current model, but a larger sample size of a broader demographic spectrum and dosing regimen would help improve the general applicability of this ratio-based modeling. Finally, we show that the mean blood-to-plasma ratio for ZOP and N-DMZOP were 0.79 and 0.92, respectively, suggesting a preferential partitioning of ZOP into the plasma fraction, which would be a useful reference when interpreting plasma concentrations from clinical studies against the more routinely sampled whole blood concentrations found in forensic toxicological casework.<\/jats:p>","DOI":"10.1093\/jat\/bkag032","type":"journal-article","created":{"date-parts":[[2026,5,28]],"date-time":"2026-05-28T11:46:22Z","timestamp":1779968782000},"source":"Crossref","is-referenced-by-count":0,"title":["Blood pharmacokinetics and use of metabolite-to-parent ratios to predict time of last zopiclone intake"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8873-8993","authenticated-orcid":false,"given":"Munchelou M","family":"Gomonit","sequence":"first","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine Forensic Toxicology Laboratory, , Gainesville, FL 32607,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnel H","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]},{"name":"Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Link\u00f6ping University , 581 83, Link\u00f6ping,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Nystr\u00f6m","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liselotte","family":"Berglund","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7886-631X","authenticated-orcid":false,"given":"Fredrik C","family":"Kugelberg","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]},{"name":"Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Link\u00f6ping University , 581 83, Link\u00f6ping,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0209-9967","authenticated-orcid":false,"given":"Maria D","family":"Cherm\u00e1","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1677-0056","authenticated-orcid":false,"given":"Johan","family":"Ahlner","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]},{"name":"Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Link\u00f6ping University , 581 83, Link\u00f6ping,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3747-5379","authenticated-orcid":false,"given":"Michael T","family":"Truver","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine Forensic Toxicology Laboratory, , Gainesville, FL 32607,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4222-9597","authenticated-orcid":false,"given":"Robert","family":"Kronstrand","sequence":"additional","affiliation":[{"name":"Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine , Artillerigatan 12, 587 58, Link\u00f6ping,","place":["Sweden"]},{"name":"Department of Biomedical and Clinical Sciences, Division of Clinical Chemistry and Pharmacology, Link\u00f6ping University , 581 83, 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