{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T04:59:41Z","timestamp":1776229181658,"version":"3.50.1"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"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":[[2026,4,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The SIGNIFY\u2122 ER test for diphenhydramine (DPH) overdose yields false-positive results for tricyclic antidepressants (TCA) in multiple cases, complicating the identification of the causative substance of poisoning. We investigated the causes of TCA false positives in DPH overdose cases. From March 2021 to September 2023, 11 cases of DPH overdose with no concomitant TCA use were identified and categorized into two groups: four with false-positive TCA results (FPG) and seven with negative results (NG) in SIGNIFY\u2122 ER. The blood and urinary DPH concentrations and the urinary concentrations of its three major metabolites (diphenhydramine N-oxide, DPH-NO; N-desmethyl diphenhydramine, DM-DPH; and diphenhydramine N-glucuronide, DPHG) were measured using liquid chromatography quadrupole time-of-flight mass spectrometry, and differences between the groups were examined. Standard substances of DPH, DPH-NO, DM-DPH, DPHG, and mixtures of DPH-NO and DPHG at ratios of 50:50, 25:75, and 75:25 were added to blank urine samples, and TCA was measured using the SIGNIFY\u2122 ER. The concentrations of the substances in the FPG and NG, respectively, were: blood DPH, 0.9\u20139 and 0.33\u201349\u2009\u00b5g\/mL; urinary DPH, 10\u2013110 and 2.3\u201336\u2009\u00b5g\/mL; urinary DPH-NO, 110\u2013170 and 0.05\u201310\u2009\u00b5g\/mL; urinary DM-DPH, 5.3\u201347 and 0.13\u20133.4\u2009\u00b5g\/mL; and urinary DPHG, 28\u2013370 and 0.24\u201367\u2009\u00b5g\/mL. When using spiked urine samples, false positives were obtained for DPH, DPH-NO, DM-DPH, and DPHG at 500, 110, 200, and 70\u2009\u00b5g\/mL, respectively. In the mixtures of DPH-NO and DPHG, false positives were obtained at all three ratios. TCA false positives in the SIGNIFY\u2122 ER test for DPH overdose cases are suggested to be yielded by DPH-NO and DPHG. For a positive test result without information on TCA use, DPH overdose should be considered.<\/jats:p>","DOI":"10.1093\/jat\/bkaf077","type":"journal-article","created":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T11:52:41Z","timestamp":1755085961000},"source":"Crossref","is-referenced-by-count":2,"title":["SIGNIFY\u2122 ER tricyclic antidepressant false positives in diphenhydramine overdose cases"],"prefix":"10.1093","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5972-1046","authenticated-orcid":false,"given":"Noriko","family":"Nishimura","sequence":"first","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0977-5043","authenticated-orcid":false,"given":"Sayaka","family":"Nagasawa","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]},{"name":"Laboratory of Forensic Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University , Chiba, 260-8675,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Go","family":"Inokuchi","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]},{"name":"Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo , Tokyo, 113-0033,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fumiko","family":"Chiba","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]},{"name":"Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo , Tokyo, 113-0033,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yumi","family":"Hoshioka","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoki","family":"Saito","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maiko","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , Chiba, 260-8670,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeki","family":"Tsuneya","sequence":"additional","affiliation":[{"name":"Department of Legal Medicine, Graduate School of Medicine, Chiba University , 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