{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:02:58Z","timestamp":1784289778701,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:00:00Z","timestamp":1784246400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Vet Pharm &amp; Therapeutics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Diazepam (DZP), a benzodiazepine sedative, has been increasingly detected in various aquatic products including fish, shrimp, and crab in recent surveillance studies, raising public health concerns. This study systematically investigates the residue behavior, metabolite profile, and dietary risk of DZP in grass carp (\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Ctenopharyngodon idella<\/jats:italic>\n                    <\/jats:styled-content>\n                    ) following oral administration at a dose of 500\u2009\u03bcg\/kg body weight. Concentrations of DZP and its metabolites in plasma and tissues were determined using ultra\u2010high performance liquid chromatography\u2013tandem mass spectrometry (UPLC\u2013MS\/MS), and the drug concentration\u2010time data were fitted using a non\u2010compartmental model embedded in WinNonLin 6.1 pharmacokinetic software. The results indicate that DZP exhibits prolonged elimination kinetics, with tissue elimination half\u2010lives (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>\n                      1\/2\n                      <jats:italic>\u03bbz<\/jats:italic>\n                    <\/jats:sub>\n                    ) ranging from 309.44 to 509.75\u2009h, and residues in skin\u2010on muscle did not fall below the limit of quantification until 98\u2009days. Metabolite analysis identified nordiazepam as the primary metabolite, with its concentration surpassing that of the parent compound by Day 21 post\u2010administration, establishing it as a reliable residue marker for DZP in grass carp. The peak human health risk index (HRI) value was 0.392 on Day 4, remaining above the alert threshold (HRI \u2265\u20090.1) for 21\u2009days, though all values remained below the safety limit (HRI &lt;\u20091). These findings provide critical data to support the regulation of aquaculture practices and the assessment of dietary exposure risks associated with DZP\u2010contaminated aquatic products.\n                  <\/jats:p>","DOI":"10.1111\/jvp.70097","type":"journal-article","created":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:04:46Z","timestamp":1784286286000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Residue Kinetics and Dietary Risk Assessment of Diazepam and Its Metabolites in Grass Carp (\n                    <i>Ctenopharyngodon idella<\/i>\n                    ): Implications for Aquaculture Safety"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6095-3602","authenticated-orcid":false,"given":"Qi","family":"Shan","sequence":"first","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Xu","sequence":"additional","affiliation":[{"name":"Chongqing Fisheries Technical Extension Center  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyuan","family":"Wu","sequence":"additional","affiliation":[{"name":"Guangxi Academy of Fishery Sciences  Nanning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiqing","family":"Mei","sequence":"additional","affiliation":[{"name":"Chongqing Fisheries Technical Extension Center  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawei","family":"Lin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisha","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichun","family":"Li","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shugui","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuliang","family":"Zhai","sequence":"additional","affiliation":[{"name":"Chongqing Fisheries Technical Extension Center  Chongqing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6259-6194","authenticated-orcid":false,"given":"Yi","family":"Yin","sequence":"additional","affiliation":[{"name":"Key Laboratory of Prevention and Control for Aquatic Invasive Alien Species, Ministry of Agriculture and Rural Affairs, Guangdong Provincial Key Laboratory of Aquatic Animal Immunology and Sustainable Aquaculture, Pearl River Fisheries Research Institute Chinese Academy of Fishery Sciences  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,17]]},"reference":[{"key":"e_1_2_10_2_1","first-page":"37","article-title":"Acute Exposure to Waterborne Psychoactive Drugs Attract 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S.","year":"2016","journal-title":"Comparative Biochemistry and Physiology, Part C: Toxicology & Pharmacology"},{"key":"e_1_2_10_3_1","first-page":"453","article-title":"Pharmacological Mechanisms of Diazepam in Fish I. Effect on Growth","volume":"5","author":"Belal I.","year":"2011","journal-title":"Journal of Environmental Science & Engineering"},{"issue":"19","key":"e_1_2_10_4_1","doi-asserted-by":"crossref","first-page":"7390","DOI":"10.1080\/03067319.2024.2445748","article-title":"Determination and Risk Assessment of Diazepam Residues in Aquatic Products From China","volume":"105","author":"Chen X.","year":"2025","journal-title":"International Journal of Environmental Analytical Chemistry"},{"issue":"1","key":"e_1_2_10_5_1","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/YCO.0b013e32831a473d","article-title":"Current Use of Benzodiazepines in Anxiety Disorders","volume":"22","author":"Cloos J.\u2010M.","year":"2009","journal-title":"Current Opinion in Psychiatry"},{"key":"e_1_2_10_6_1","unstructured":"CMARA.2019.\u201cNational Food Safety Standard\u2010Maximum Residue Limits for Veterinary Drugs in Foods.\u201dhttp:\/\/down.foodmate.net\/standard\/sort\/3\/64074.html."},{"key":"e_1_2_10_7_1","volume-title":"China Fishery Statistical Yearbook","author":"CMARA","year":"2024"},{"key":"e_1_2_10_8_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.envpol.2025.127038","article-title":"Study on the Residual Dynamics of Diazepam in Freshwater Fish of Zhejiang, China and Its Implications for Human Health","volume":"384","author":"Cui J.","year":"2025","journal-title":"Environmental Pollution"},{"issue":"31","key":"e_1_2_10_9_1","doi-asserted-by":"crossref","first-page":"24076","DOI":"10.1007\/s11356-017-0170-4","article-title":"Psychoactive Drugs: Occurrence in Aquatic Environment, Analytical Methods, and Ecotoxicity\u2014A Review","volume":"24","author":"Cunha D. L.","year":"2017","journal-title":"Environmental Science and Pollution Research"},{"issue":"1","key":"e_1_2_10_10_1","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/s13311-019-00827-z","article-title":"The Long and the Short of Benzodiazepines and Sleep Medications: Short\u2010Term Benefits, Long\u2010Term Harms?","volume":"17","author":"DeKosky S. T.","year":"2020","journal-title":"Neurotherapeutics"},{"issue":"1","key":"e_1_2_10_11_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0165-1110(96)90004-4","article-title":"Review of the Genotoxic Properties of Chlorpromazine and Related Phenothiazines","volume":"366","author":"Gocke E.","year":"1996","journal-title":"Mutation Research, Reviews in Genetic Toxicology"},{"issue":"2","key":"e_1_2_10_12_1","first-page":"214","article-title":"Benzodiazepine Pharmacology and Central Nervous System\u2010Mediated Effects","volume":"13","author":"Griffin C. E.","year":"2013","journal-title":"Ochsner Journal"},{"issue":"24","key":"e_1_2_10_13_1","doi-asserted-by":"crossref","DOI":"10.3390\/app10249083","article-title":"Assessment of Dietary Exposure and Risk of DDT Concerning Freshwater Fish Aquaculture","volume":"10","author":"Kasza G.","year":"2020","journal-title":"Applied Sciences"},{"key":"e_1_2_10_14_1","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/j.aquaculture.2017.07.034","article-title":"Residual Levels and Risk Assessment of Eugenol and Its Isomers in Fish From China Markets","volume":"484","author":"Ke C.","year":"2018","journal-title":"Aquaculture (Amsterdam, Netherlands)"},{"key":"e_1_2_10_15_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.chemosphere.2022.135657","article-title":"Residue, Biotransformation, Risk Assessment and Withdrawal Time of Enrofloxacin in Red Swamp Crayfish (\n                     Procambarus clarkii\n                  )","volume":"307","author":"Liu Y.","year":"2022","journal-title":"Chemosphere"},{"key":"e_1_2_10_16_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2021.114515","article-title":"Diazepam Effects on Local Cortical Neural Activity During Sleep in Mice","volume":"191","author":"McKillop L. E.","year":"2021","journal-title":"Biochemical Pharmacology"},{"issue":"19","key":"e_1_2_10_17_1","doi-asserted-by":"crossref","first-page":"18226","DOI":"10.1007\/s11356-017-8902-z","article-title":"Pharmaceuticals and Illicit Drugs in Wastewater Samples in North\u2010Eastern Tunisia","volume":"25","author":"Moslah B.","year":"2018","journal-title":"Environmental Science and Pollution Research"},{"key":"e_1_2_10_18_1","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.cbpc.2016.02.001","article-title":"Bioconcentration and Endocrine Disruption Effects of Diazepam in Channel Catfish, \n                     Ictalurus punctatus","volume":"183","author":"Overturf C. L.","year":"2016","journal-title":"Comparative Biochemistry and Physiology. Toxicology & Pharmacology"},{"issue":"3","key":"e_1_2_10_19_1","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/jvp.13505","article-title":"Residue Behavior and Risk Assessment of Diazepam and Its Metabolites in Crucian Carp (\n                     Carassius auratus\n                  ) After Oral Administration","volume":"48","author":"Shan Q.","year":"2025","journal-title":"Journal of Veterinary Pharmacology and Therapeutics"},{"issue":"1","key":"e_1_2_10_20_1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1080\/01919510701799278","article-title":"Occurrence, Treatment, and Toxicological Relevance of EDCs and Pharmaceuticals in Water","volume":"30","author":"Snyder S. A.","year":"2008","journal-title":"Ozone: Science & Engineering"},{"issue":"11","key":"e_1_2_10_21_1","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1002\/etc.3876","article-title":"Occurrence and Human Dietary Assessment of Fluoroquinolones Antibiotics in Cultured Fish Around Tai Lake, China","volume":"36","author":"Song C.","year":"2017","journal-title":"Environmental Toxicology and Chemistry"},{"issue":"3","key":"e_1_2_10_22_1","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.bja.2021.10.029","article-title":"Mechanisms of Respiratory Depression Induced by the Combination of Buprenorphine and Diazepam in Rats","volume":"128","author":"Vodovar D.","year":"2022","journal-title":"British Journal of Anaesthesia"},{"issue":"1","key":"e_1_2_10_23_1","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1007\/s40268-021-00375-y","article-title":"Pharmacokinetics of Diazepam and Its Metabolites in Urine of Chinese Participants","volume":"22","author":"Wang L. L.","year":"2022","journal-title":"Drugs in R&D"},{"key":"e_1_2_10_24_1","first-page":"31","article-title":"Diazepam and Nordiazepam Residue in the Aquatic Product From Market in Shanghai","volume":"03","author":"Wang s.","year":"2020","journal-title":"Agricultural Product Quality and Safety"},{"issue":"6","key":"e_1_2_10_25_1","first-page":"38","article-title":"Effects of Diazepam in Water on Residues of Diazepam and Its Metabolites in Grass Carp Muscle and Assessment of Consumption Related Health Risks","volume":"14","author":"Xu X.","year":"2024","journal-title":"Chinese Fishery Quality and Standards"},{"issue":"4","key":"e_1_2_10_26_1","first-page":"1","article-title":"Investigation of Diazepam Content in Fish Bait and Analysis of Its Impact on Aquaculture","volume":"12","author":"Yang G.","year":"2022","journal-title":"China Fishery Quality and Standards"},{"issue":"8","key":"e_1_2_10_27_1","first-page":"3300","article-title":"Screening of Diazepam Content in Aquaculture Water Based on High Resolution Mass Spectrometry","volume":"12","author":"Yang\u2010Feng L.","year":"2021","journal-title":"Journal of Food Safety and Quality"},{"issue":"1","key":"e_1_2_10_28_1","first-page":"54","article-title":"Determination of Diazepam and Its Residue in Turbot and Mandarinfish by High Performance Liquid Chromatography\u2010Tandem Mass Spectrometry","volume":"1","author":"Yu H.","year":"2011","journal-title":"Chinese Fishery Quality and Standards"},{"issue":"12","key":"e_1_2_10_29_1","first-page":"198","article-title":"Determination of Diazepam in Aquatic Products by Dispersive Solid Phase Extraction\u2010Ultra Performance Liquid Chromatography Tandem Mass Spectrometry","volume":"49","author":"Zeng J.","year":"2021","journal-title":"Anhui Agricultural Science"}],"container-title":["Journal of Veterinary Pharmacology and Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.70097","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvp.70097","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvp.70097","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T11:04:52Z","timestamp":1784286292000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvp.70097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,17]]},"references-count":28,"alternative-id":["10.1111\/jvp.70097"],"URL":"https:\/\/doi.org\/10.1111\/jvp.70097","archive":["Portico"],"relation":{},"ISSN":["0140-7783","1365-2885"],"issn-type":[{"value":"0140-7783","type":"print"},{"value":"1365-2885","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,17]]},"assertion":[{"value":"2026-03-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"jvp.70097"}}