{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T11:35:17Z","timestamp":1780054517098,"version":"3.54.0"},"reference-count":19,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2019,8,22]],"date-time":"2019-08-22T00:00:00Z","timestamp":1566432000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"National Institute of Justice, Research and Development in Forensic Science for Criminal Justice Purposes","award":["2016-DN-BX-0148"],"award-info":[{"award-number":["2016-DN-BX-0148"]}]},{"name":"National Institute of Justice, Research and Development in Forensic Science for Criminal Justice Purposes","award":["2017-R2-CX-0029"],"award-info":[{"award-number":["2017-R2-CX-0029"]}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DA03393"],"award-info":[{"award-number":["P30DA03393"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Virginia Commonwealth University Undergraduate Research Opportunities Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Opioid usage in the USA has increased over the past decade, with prescriptions increasing from 76\u00a0million in 1991 to 207\u00a0million in 2013. New regulations have curbed the number of prescriptions, leading to an increase in heroin use. Heroin-related overdoses have quadrupled between 2000 and 2015. The traditional urinary biomarkers for indicating heroin use are a combination of morphine and 6-acetyl morphine (6-AM). Morphine is detectable in urine for several days. 6-AM is detected in urine for 2\u20138\u00a0hours. Papaverine has been proposed as an alternative heroin biomarker. It has been reported to have a 1\u20132\u00a0day detection window. Papaverine metabolites have been reported to have up to a 3-day detection window. Presented is a method for the detection of papaverine and its metabolites, 6-desmethyl papaverine (6-DMP) and 4\u2032, 6-didesmethyl papaverine (4,6-DDMP), in urine using a modified Waters\u00ae MCX\u2122 microelution method. An ultra-performance liquid chromatography and tandem mass spectrometry (UPLC\u2013MS-MS), with a Waters\u2019 BEH C18 column, and 20\u00a0mM ammonium formate water: 20\u00a0mM ammonium formate methanol mobile phase was employed. Calibration curves were linear from 0.1 to 50\u00a0ng\/mL. No interferences were observed from the analysis of multicomponent therapeutic drug or drugs of abuse control materials; intra- and inter-run precision tests were acceptable. A total of 428 genuine urine specimens where heroin use was suspected were analyzed. These included 101 6-AM and 179 morphine only positive samples as well as 6 morphine-negative samples where papaverine and\/or metabolites were detected. The determined concentrations in these samples for papaverine, 6-DMP and 4,6-DDMP ranged from 0.10 to 994, 0.10 to 462 and 0.12 to 218\u00a0ng\/mL, respectively. The method was rugged and robust for the analysis of papaverine and metabolites, 6-DMP and 4,6-DDMP. The use papaverine and metabolites, 6-DMP and 4,6-DDMP has the potential to increase the detection window of heroin use.<\/jats:p>","DOI":"10.1093\/jat\/bkz069","type":"journal-article","created":{"date-parts":[[2019,7,15]],"date-time":"2019-07-15T15:09:25Z","timestamp":1563203365000},"page":"600-606","source":"Crossref","is-referenced-by-count":8,"title":["Using Papaverine and Its Metabolites, 6-Desmethyl Papaverine and 4\u2032,6-Didesmethyl Papaverine as Biomarkers to Improve the Detection Time of Heroin Use"],"prefix":"10.1093","volume":"43","author":[{"given":"Carl E","family":"Wolf","sequence":"first","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlin L","family":"Pierce","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brett L","family":"Goldfine","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrol R","family":"Nanco","sequence":"additional","affiliation":[{"name":"Pathology"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin L","family":"Poklis","sequence":"additional","affiliation":[{"name":"Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William J","family":"Korzun","sequence":"additional","affiliation":[{"name":"Clinical Laboratory Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,8,21]]},"reference":[{"key":"2019121714372739700_ref1","volume-title":"Overdose Death Rates","author":"National Institute on Drug Abuse (NIDA)","year":"2017"},{"key":"2019121714372739700_ref2","first-page":"1","article-title":"Prevalence of chronic pain and high-impact chronic pain among adults = United States, 2016","volume":"67","author":"Dahlhamer","journal-title":"Morbidity and Mortality Weekly Report"},{"key":"2019121714372739700_ref3","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.forsciint.2014.04.037","article-title":"Prevalence of heroin markers in urine for pain management patients","volume":"243","author":"Knight","year":"2014","journal-title":"Forensic Science International"},{"key":"2019121714372739700_ref4","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1007\/s12024-016-9780-2","article-title":"Identifying cases of heroin toxicity where 6-acetylmorphine (6-AM) is not detected by toxicological analyses","volume":"12","author":"Ellis","year":"2016","journal-title":"Forensic Science, Medicine, and Pathology"},{"key":"2019121714372739700_ref5","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1097\/00007691-200608000-00011","article-title":"The significance of putative urinary markers of illicit heroin use after consumption of poppy seed 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indicators of heroin ingestion","volume":"30","author":"Paterson","year":"2006","journal-title":"Journal of Analytical Toxicology"},{"key":"2019121714372739700_ref12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1080\/14659890802581628","article-title":"Validity of noscapine and papaverine metabolites as markers of heroin misuse in the context of diamorphine treatment. A survey of urine samples from nonsubstance misusing patients prescribed diamorphine","volume":"14","author":"Trathen","year":"2009","journal-title":"Journal of Substance Use"},{"key":"2019121714372739700_ref13","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/jat\/bks099","article-title":"Biomarkers for illicit heroin: A previously unrecognized origin of papaverine","volume":"37","author":"Nitin Seetohul","year":"2013","journal-title":"Journal of Analytical Toxicology"},{"key":"2019121714372739700_ref14","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.jflm.2018.12.005","article-title":"Metabolism and metabolomics of opiates: A long way of forensic implications to unravel","volume":"61","author":"Dinis-Oliveiraa","year":"2019","journal-title":"Journal of Forensic and Legal Medicine"},{"key":"2019121714372739700_ref15","doi-asserted-by":"crossref","first-page":"297","DOI":"10.3109\/00498257809060953","article-title":"Metabolism of Papaverine IV. 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