{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T12:32:09Z","timestamp":1782736329216,"version":"3.54.5"},"reference-count":39,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T00:00:00Z","timestamp":1764288000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Zhejiang Provincial Natural Science Foundation of China","award":["LTGN23C200003"],"award-info":[{"award-number":["LTGN23C200003"]}]},{"DOI":"10.13039\/501100008990","name":"Department of Science and Technology of Zhejiang Province","doi-asserted-by":"crossref","award":["HYS-CZ-202503"],"award-info":[{"award-number":["HYS-CZ-202503"]}],"id":[{"id":"10.13039\/501100008990","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>A method combining magnetic solid-phase extraction (MSPE) with ultra-high performance liquid chromatography\u2013tandem mass spectrometry (UPLC-MS\/MS) was developed for the determination of diazepam residues in aquatic products. A novel magnetic nanoparticle material, Fe3O4@SiO2@DVB-NVP, was synthesized and applied as an adsorbent for sample cleanup. The sample preparation procedure involved extraction with 1% ammonia\u2013acetonitrile, followed by purification using the MSPE technique to efficiently remove matrix interferents. Chromatographic separation was achieved on an ACQUITY UPLC BEH C18 column with a gradient elution program using a mobile phase composed of 0.1% formic acid\u20132 mM ammonium acetate solution and methanol. Detection was performed under multiple-reaction monitoring (MRM) mode with positive electrospray ionization (ESI+). Quantification was carried out using the external standard method. The synthesized magnetic material was characterized using SEM, TEM, FTIR, XRD, BET, and VSM, confirming its mesoporous structure, strong adsorption capacity, and excellent magnetic responsiveness. The method demonstrated good linearity over the concentration range of 0.25\u201350 \u03bcg\/L (r2 = 0.997). The limits of detection and quantification were 0.20 \u03bcg\/kg and 0.50 \u03bcg\/kg, respectively. Average recoveries from spiked blank matrices at three levels (0.5, 2.5, and 5.0 \u03bcg\/kg) ranged from 89.3% to 119.7%, with relative standard deviations (RSDs) between 0.8% and 10.2%. The proposed method is highly selective, exhibits minimal matrix interference, and provides reliable quantitative performance, making it suitable for the qualitative and quantitative analysis of diazepam residues in aquatic products.<\/jats:p>","DOI":"10.3390\/foods14234087","type":"journal-article","created":{"date-parts":[[2025,11,28]],"date-time":"2025-11-28T12:14:16Z","timestamp":1764332056000},"page":"4087","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Quantitative Analysis of Diazepam Residues in Aquatic Products Using Magnetic Solid-Phase Extraction Combined with Ultra-High-Performance Liquid Chromatography\u2013Tandem Mass Spectrometry"],"prefix":"10.3390","volume":"14","author":[{"given":"Mengqiong","family":"Yang","sequence":"first","affiliation":[{"name":"College of Food and Pharmaceutical Science, Zhejiang Ocean University, Zhoushan 316022, China"},{"name":"Zhejiang Marine Fisheries Research Institute, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9267-8112","authenticated-orcid":false,"given":"Guangming","family":"Mei","sequence":"additional","affiliation":[{"name":"Zhejiang Marine Fisheries Research Institute, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daoxiang","family":"Huang","sequence":"additional","affiliation":[{"name":"College of Food and Pharmaceutical Science, Zhejiang Ocean University, Zhoushan 316022, China"},{"name":"Zhejiang Marine Fisheries Research Institute, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Zhejiang Marine Fisheries Research Institute, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"He","sequence":"additional","affiliation":[{"name":"Zhejiang Marine Fisheries Research Institute, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,28]]},"reference":[{"key":"ref_1","first-page":"86","article-title":"Effects of Phenobarbital sodium combined with Diazepam in treatment of children with febrile convulsion","volume":"36","author":"Ma","year":"2024","journal-title":"Med. J. Chin. People\u2019s Health"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"109987","DOI":"10.1016\/j.yebeh.2024.109987","article-title":"Treatment of prolonged seizure with diazepam nasal spray: An exploratory post hoc cohort analysis","volume":"159","author":"Jarrar","year":"2024","journal-title":"Epilepsy Behav."},{"key":"ref_3","first-page":"106","article-title":"Analysis of the sedative effects of midazolam and diazepam on patients with severe tetanus","volume":"18","author":"Wang","year":"2024","journal-title":"Mod. Drug Appl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"100644","DOI":"10.1016\/j.ebr.2024.100644","article-title":"Analyses of Patients Who Self-Administered Diazepam Nasal Spray for Acute Treatment of Seizure Clusters","volume":"25","author":"Misra","year":"2024","journal-title":"Epilepsy Behav. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Hsu, W., Chen, C., Liang, H., Chiang, T., Lin, H., and Lin, Y. (2024). Innovative Analysis of Diazepam, Zolpidem and Their Main Metabolites in Human Urine by Micelle-to-Solvent Stacking in Capillary Electrophoresis. J. Pharm. Biomed. Anal., 239.","DOI":"10.1016\/j.jpba.2023.115898"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8878143","DOI":"10.1155\/2020\/8878143","article-title":"Diazepam and its disinfection byproduct promote the early development of nervous system in zebrafish embryos","volume":"2020","author":"Zhao","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.vaa.2024.12.007","article-title":"Pharmacokinetics of remimazolam, midazolam and diazepam in sheep","volume":"52","author":"Burbery","year":"2025","journal-title":"Vet. Anaesth. Analg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"123216","DOI":"10.1016\/j.lfs.2024.123216","article-title":"Does concomitant diazepam and ethanol use modulate age-related cognitive decline in mice?","volume":"359","author":"Carton","year":"2024","journal-title":"Life Sci."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.chemosphere.2018.11.076","article-title":"Determination of emerging chlorinated byproducts of diazepam in drinking water","volume":"218","author":"Zhang","year":"2019","journal-title":"Chemosphere"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"127038","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","year":"2025","journal-title":"Environ. Pollut."},{"key":"ref_11","unstructured":"(2019). National Health Commission of the People\u2019s Republic of China, State Administration for Market Regulation. National Food Safety Standard on Maximum Residue Limits for Veterinary Drugs in Foods (Standard No. GB31650-2019)."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"138493","DOI":"10.1016\/j.foodchem.2024.138493","article-title":"One Step Cleanup of 160 Pesticides and Veterinary Drugs in Aquatic Products Using Melamine-Based Automatic Pressure Filtration Purification Method Combined with HPLC-MS\/MS","volume":"443","author":"Zhou","year":"2024","journal-title":"Food Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/0009-8981(86)90059-8","article-title":"Enzyme-Linked Immunosorbent Assay for Amitriptyline and Other Antidepressants Using a Monoclonal Antibody","volume":"159","author":"Denis","year":"1986","journal-title":"Clin. Chim. Acta"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3487","DOI":"10.1021\/acschemneuro.3c00346","article-title":"Adinazolam, a Benzodiazepine-Type New Psychoactive Substance, Has Abuse Potential and Induces Withdrawal Symptoms in Rodents","volume":"14","author":"Hwang","year":"2023","journal-title":"ACS Chem. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Tok, K.C., Ozkan-Kotiloglu, S., Bozmaoglu, C.H., Danisman, M., Ozgur-Ilhan, I., Kaya-Akyuzlu, D., Suzen, H.S., and Gumustas, M. (2025). Development of a sample preparation and analysis method for therapeutic monitoring of diazepam and major metabolite in alcohol withdrawal syndrome treatment. J. Pharm. Biomed. Anal., 260.","DOI":"10.1016\/j.jpba.2025.116805"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"137191","DOI":"10.1016\/j.foodchem.2023.137191","article-title":"Exploiting the potential of fabric phase sorptive extraction for forensic food safety: Analysis of food samples in cases of drug facilitated crimes","volume":"432","author":"Jain","year":"2024","journal-title":"Food Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jchromb.2008.08.027","article-title":"High-Performance Liquid Chromatography Coupled with Electrospray Tandem Mass Spectrometry (LC\/MS\/MS) Method for the Simultaneous Determination of Diazepam, Atropine and Pralidoxime in Human Plasma","volume":"874","author":"Abbara","year":"2008","journal-title":"J. Chromatogr. B"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xiao, N., Li, X., Li, W., Zhao, J., Li, Y., and Wang, L. (2024). Pharmacokinetic study of Q808 in rhesus monkey using liquid chromatography-tandem mass spectrometry. Front. Pharmacol., 15.","DOI":"10.3389\/fphar.2024.1433043"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"112354","DOI":"10.1016\/j.microc.2024.112354","article-title":"A comparative study of SPE- and DLLME-based methods for the determination of opioids and benzodiazepines in urine samples using LC-MS\/MS","volume":"208","author":"Rosendo","year":"2025","journal-title":"Microchem. J."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s12247-016-9246-9","article-title":"Preparation and evaluation of long-circulating deoxypodophyllotoxin-loaded liposomes using poly(ethylene glycol)-distearoylphosphatidylethanolamine","volume":"11","author":"Wang","year":"2016","journal-title":"J. Pharm. Innovation"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Tejedor, A.M.G., Yague, J.C.B., Gonzalez, G.P., Martinez, R.M.G., and Hernando, P.F. (2024). Selective extraction of diazepam and its metabolites from urine samples by a molecularly imprinted solid-phase extraction (MISPE) method. Polymers, 16.","DOI":"10.3390\/polym16050635"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1080\/00032719.2015.1076830","article-title":"Determination of Benzodiazepines in Beef by Magnetic Solid Phase Extraction and High-Performance Liquid Chromatography-Tandem Mass Spectrometry","volume":"49","author":"Kuang","year":"2016","journal-title":"Anal. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"135221","DOI":"10.1016\/j.scitotenv.2019.135221","article-title":"Development, Validation, Comparison, and Implementation of a Highly Efficient and Effective Method Using Magnetic Solid-Phase Extraction with Hydrophilic-Lipophilic-Balanced Materials for LC-MS\/MS Analysis of Pesticides in Seawater","volume":"708","author":"Liu","year":"2020","journal-title":"Sci. Total Environ."},{"key":"ref_24","unstructured":"Zhang, Z. (2022). Research on Preparation and Electromagnetic Properties of Rare Earth Composite Metal Nanoparticles. [Master\u2019s Thesis, Northeastern University]."},{"key":"ref_25","unstructured":"(2014). General Administration of Quality Supervision, Inspection and Quarantine of the People\u2019s Republic of China, Standardization Administration of the People\u2019s Republic of China. Sampling Specification for Aquatic Products (Standard No. GB\/T 30891-2014)."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"113459","DOI":"10.1016\/j.microc.2025.113459","article-title":"Evaluation of Matrix Effects on Automated Nutrient Determination in Seawater Using Segmented Flow Analysis","volume":"212","author":"Zhu","year":"2025","journal-title":"Microchem. J."},{"key":"ref_27","first-page":"2425","article-title":"Preparation of magnetic Fe3O4@ZrP composites and its La3+ adsorption performance","volume":"42","author":"Liu","year":"2025","journal-title":"Fine Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"28839","DOI":"10.1021\/acsami.8b08040","article-title":"Optimizing the Electromagnetic Wave Absorption Performances of Designed Co3Fe7@C Yolk-Shell Structures. ACS Appl","volume":"10","author":"Li","year":"2018","journal-title":"Mater. Interfaces"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Li, P., Chen, Y., Bai, J., Yang, H., He, P., and Zeng, J. (2025). The determination of eight biogenic amines using MSPE-UHPLC-MS\/MS and their application in regard to changes in these biogenic amines in traditional Chinese dish-pickled swimming crabs. Molecules, 30.","DOI":"10.3390\/molecules30061353"},{"key":"ref_30","unstructured":"(2012). Industry Standard of the People\u2019s Republic of China for Entry-Exit Inspection and Quarantine. Determination of Multi-Groups of Banned Drug Residues in Foodstuffs of Animal Origin for Export-LC-MS\/MS Method (Standard No. SN\/T 3235-2012)."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Chen, X., Fang, H., Li, J., Shi, S., Pu, Y., He, Y., Liu, Z., Cheng, L., Liu, H., and Lin, T. (2025). Determination and risk assessment of diazepam residues in aquatic products from China. Int. J. Environ. Anal. Chem., 1\u201318.","DOI":"10.1080\/03067319.2024.2445748"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1080\/19440049.2022.2032381","article-title":"Simultaneous Determination of the Four Key Fluoroquinolones and Two Antipsychotics in Fish and Shrimp by LC-MS\/MS","volume":"39","author":"Shen","year":"2022","journal-title":"Food Addit. Contam. A"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Sebihi, S., Monperrus, M., Coste, P., Huchet, E., Lingrand, M., Glise, S., Bouchard, C., Ortiz-Zarragoitia, M., and Bolliet, V. (2025). An Optimized Whole-Body Corticosteroid Hormones Quantification Method by LC-MS\/MS for Assessing Stress Levels in European Glass Eels (Anguilla anguilla). J. Steroid Biochem. Mol. Biol., 245.","DOI":"10.1016\/j.jsbmb.2024.106627"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1002\/jsfa.7123","article-title":"A Comparative Study of Primary Secondary Amino (PSA) and Multi-Walled Carbon Nanotubes (MWCNTs) as QuEChERS Absorbents for the Rapid Determination of Diazepam and Its Major Metabolites in Fish Samples by High-Performance Liquid Chromatography-Electrospray Ionisation-Tandem Mass Spectrometry","volume":"96","author":"Li","year":"2016","journal-title":"J. Sci. Food Agric."},{"key":"ref_35","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 (Carassius auratus) after oral administration","volume":"48","author":"Shan","year":"2025","journal-title":"J. Vet. Pharmacol. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"101268","DOI":"10.1016\/j.fochx.2024.101268","article-title":"A Modified QuEChERS-Based UPLC-MS\/MS Method for Rapid Determination of Multiple Antibiotics and Sedative Residues in Freshwater Fish","volume":"22","author":"Yang","year":"2024","journal-title":"Food Chem. X"},{"key":"ref_37","first-page":"195","article-title":"Determination of diazepam and eugenol residues in aquatic products based on ultra performance liquid chromatography-electrostatic field orbital high resolution mass spectrometry","volume":"15","author":"Yin","year":"2024","journal-title":"J. Food Saf. Qual."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1039\/D4AY02144D","article-title":"Determination of diazepam and its active metabolites in aquatic products and aquaculture environments using modified QuEChERS-based UPLC-MS\/MS","volume":"17","author":"Zhou","year":"2025","journal-title":"Anal. Methods"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Yang, M., Mei, G., Huang, D., Zhang, X., He, P., and Chen, S. (2025). Matrix interference removal using Fe3O4@SiO2-PSA-based magnetic dispersive solid-phase extraction for UPLC-MS\/MS analysis of diazepam in aquatic products. Foods, 14.","DOI":"10.3390\/foods14142421"}],"container-title":["Foods"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/23\/4087\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,30]],"date-time":"2025-11-30T05:12:26Z","timestamp":1764479546000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2304-8158\/14\/23\/4087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,28]]},"references-count":39,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["foods14234087"],"URL":"https:\/\/doi.org\/10.3390\/foods14234087","relation":{},"ISSN":["2304-8158"],"issn-type":[{"value":"2304-8158","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,28]]}}}