{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:56:06Z","timestamp":1790592966670,"version":"4.1.0"},"reference-count":34,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T00:00:00Z","timestamp":1787788800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Separation Science"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The determination of benzodiazepines and opioids in whole blood by gas chromatography (GC) remains challenging due to low analyte concentrations and matrix\u2010related effects that may compromise analytical response. In this study, the use of analyte protectants (APs) was investigated as a means of enhancing detector response in GC\u2013tandem mass spectrometry (GC\u2013MS\/MS) analysis of selected benzodiazepines and opioids following Quick, Easy, Cheap, Effective, Rugged, and Safe\u2010based sample preparation. A series of high\u2010boiling compounds, including linear alcohols, amines, carboxylic acids, and polyethylene glycols (PEGs), were evaluated as APs capable of modulating the chromatographic response. Among the tested compounds, PEG\u2010400 and PEG\u2010600 provided the most consistent signal enhancement, increasing responses of benzodiazepines by 413%\u2013475% and opioids by up to 628% under optimized conditions. Long\u2010chain amines showed the highest enhancement for selected opioids, reaching up to 1080%. The influence of key experimental parameters on APs efficiency was systematically assessed, demonstrating that acetonitrile as the extraction solvent, elevated injector temperatures (up to 325\u00b0C), and low initial oven temperatures favored signal enhancement. The developed GC\u2013MS\/MS procedure exhibited satisfactory analytical performance, including high linearity (\n                    <jats:italic>R<\/jats:italic>\n                    <jats:sup>2<\/jats:sup>\n                    &gt; 0.998), good precision (relative standard deviation &lt;5%), and low limits of quantification. Application of the approach to authentic whole\u2010blood samples confirmed that signal enhancement can also be achieved in complex biological matrices, although its magnitude was reduced by the presence of residual matrix constituents. In particular, bromazepam exhibited a 593% increase in signal following the addition of PEG\u2010400. The results demonstrate that the implementation of APs can serve as a simple means of improving analytical response in GC\u2013MS\/MS analysis of benzodiazepines and opioids without modification of routine sample preparation procedures. The findings further contribute to the understanding of protectant\u2010mediated signal enhancement mechanisms in the analysis of biological samples.\n                  <\/jats:p>","DOI":"10.1002\/jssc.70517","type":"journal-article","created":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T17:44:35Z","timestamp":1787852675000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigation and Implementation of Analyte Protectants in the Gas Chromatography\u2013Tandem Mass Spectrometry Analysis of Benzodiazepines and Opioids in Whole Blood Extracts"],"prefix":"10.1002","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1028-759X","authenticated-orcid":false,"given":"Michal P.","family":"Dybowski","sequence":"first","affiliation":[{"name":"Department of Chromatography, Institute of Chemical Sciences, Faculty of Chemistry Maria Curie\u2010Sk\u0142odowska University  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-9263-7745","authenticated-orcid":false,"given":"Krystian J.","family":"Siwek","sequence":"additional","affiliation":[{"name":"Department of Chromatography, Institute of Chemical Sciences, Faculty of Chemistry Maria Curie\u2010Sk\u0142odowska University  Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,27]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378\u20104347(97)00573\u20102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/s22041592"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2009.24.1.1"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/03602532.2019.1697283"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088\u2010199733050\u201000003"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228\u2010015\u20101832\u20100"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/healthcare10081392"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neubiorev.2015.06.012"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/neurolint13040059"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1159\/000524400"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.23247"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8836983"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/1556\u20104029.70151"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201200921"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201000921"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2010.12.113"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00414\u2010016\u20101485\u20102"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/jat\/bky017"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/ftox.2025.1639890"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200700142"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.200800447"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1360\u20100443.2007.02009.x"},{"key":"e_1_2_11_24_1","first-page":"862","article-title":"A Look at Matrix Effects","volume":"35","author":"Delaney M. 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