Multiplex detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients
•A simple quantitative LC–MS/MS method for fentanyl analogs in urine and whole blood.•Consumption of fentanyl analogs may be underestimated by immunoassay screening.•Importance of urine monitoring of the patients treated with fentanyl and analogs. Synthetic opioids (SO) associated with the recent al...
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| Veröffentlicht in: | Forensic science international 2020-12, Vol.317, p.110437, Article 110437 |
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| creator | Jung, Jean Kolodziej, Allan Pape, Elise Bisch, Michael Javot, Lucie Gibaja, Valérie Jouzeau, Jean-Yves Scala-Bertola, Julien Gambier, Nicolas |
| description | •A simple quantitative LC–MS/MS method for fentanyl analogs in urine and whole blood.•Consumption of fentanyl analogs may be underestimated by immunoassay screening.•Importance of urine monitoring of the patients treated with fentanyl and analogs.
Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5–50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region. |
| doi_str_mv | 10.1016/j.forsciint.2020.110437 |
| format | Article |
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Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5–50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.</description><identifier>ISSN: 0379-0738</identifier><identifier>EISSN: 1872-6283</identifier><identifier>DOI: 10.1016/j.forsciint.2020.110437</identifier><identifier>PMID: 33007729</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>Accuracy ; Addictions ; Adolescent ; Adult ; Aged ; Alfentanil - blood ; Alfentanil - urine ; Analgesics ; Analgesics, Opioid - blood ; Analgesics, Opioid - urine ; Benzamides - blood ; Benzamides - urine ; Biological properties ; Biological samples ; Blood ; Calibration ; Child ; Child, Preschool ; Chromatography ; Chromatography, Liquid ; Drug abuse ; Drug screening ; Female ; Fentanyl ; Fentanyl - analogs & derivatives ; Fentanyl - blood ; Fentanyl - urine ; Fentanyl analogues ; Forensic sciences ; France ; Furans - blood ; Furans - urine ; Heroin ; HPLC-MS/MS ; Humanities and Social Sciences ; Humans ; Infant ; Infant, Newborn ; Limit of Detection ; Liquid chromatography ; Liquid-liquid extraction ; Male ; Mass spectrometry ; Mass spectroscopy ; Middle Aged ; Misuse ; Multiplexing ; Narcotics ; Neonatal Abstinence Syndrome - diagnosis ; Nitrogen ; Opioids ; Piperidines - blood ; Piperidines - urine ; Remifentanil ; Remifentanil - blood ; Remifentanil - urine ; Retrospective Studies ; Scientific imaging ; Substance Abuse Detection ; Substance-Related Disorders - diagnosis ; Sufentanil ; Sufentanil - blood ; Sufentanil - urine ; Synthetic opioids ; Tandem Mass Spectrometry ; U-47700 ; Urine ; Young Adult</subject><ispartof>Forensic science international, 2020-12, Vol.317, p.110437, Article 110437</ispartof><rights>2020</rights><rights>Copyright © 2020. Published by Elsevier B.V.</rights><rights>Copyright Elsevier Limited Dec 2020</rights><rights>Attribution - NonCommercial</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-cbd89f8ff54c07b05f2c3cad25a0ea778e34d8f350d96d8130cdbf65db02b6b3</citedby><cites>FETCH-LOGICAL-c482t-cbd89f8ff54c07b05f2c3cad25a0ea778e34d8f350d96d8130cdbf65db02b6b3</cites><orcidid>0000-0003-2429-945X ; 0000-0003-3731-3433 ; 0000-0002-9863-9739</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0379073820302991$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33007729$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03492148$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Jung, Jean</creatorcontrib><creatorcontrib>Kolodziej, Allan</creatorcontrib><creatorcontrib>Pape, Elise</creatorcontrib><creatorcontrib>Bisch, Michael</creatorcontrib><creatorcontrib>Javot, Lucie</creatorcontrib><creatorcontrib>Gibaja, Valérie</creatorcontrib><creatorcontrib>Jouzeau, Jean-Yves</creatorcontrib><creatorcontrib>Scala-Bertola, Julien</creatorcontrib><creatorcontrib>Gambier, Nicolas</creatorcontrib><title>Multiplex detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients</title><title>Forensic science international</title><addtitle>Forensic Sci Int</addtitle><description>•A simple quantitative LC–MS/MS method for fentanyl analogs in urine and whole blood.•Consumption of fentanyl analogs may be underestimated by immunoassay screening.•Importance of urine monitoring of the patients treated with fentanyl and analogs.
Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5–50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.</description><subject>Accuracy</subject><subject>Addictions</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Alfentanil - blood</subject><subject>Alfentanil - urine</subject><subject>Analgesics</subject><subject>Analgesics, Opioid - blood</subject><subject>Analgesics, Opioid - urine</subject><subject>Benzamides - blood</subject><subject>Benzamides - urine</subject><subject>Biological properties</subject><subject>Biological samples</subject><subject>Blood</subject><subject>Calibration</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Chromatography</subject><subject>Chromatography, Liquid</subject><subject>Drug abuse</subject><subject>Drug screening</subject><subject>Female</subject><subject>Fentanyl</subject><subject>Fentanyl - analogs & derivatives</subject><subject>Fentanyl - blood</subject><subject>Fentanyl - urine</subject><subject>Fentanyl analogues</subject><subject>Forensic sciences</subject><subject>France</subject><subject>Furans - blood</subject><subject>Furans - urine</subject><subject>Heroin</subject><subject>HPLC-MS/MS</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Limit of Detection</subject><subject>Liquid chromatography</subject><subject>Liquid-liquid extraction</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Middle Aged</subject><subject>Misuse</subject><subject>Multiplexing</subject><subject>Narcotics</subject><subject>Neonatal Abstinence Syndrome - diagnosis</subject><subject>Nitrogen</subject><subject>Opioids</subject><subject>Piperidines - blood</subject><subject>Piperidines - urine</subject><subject>Remifentanil</subject><subject>Remifentanil - blood</subject><subject>Remifentanil - urine</subject><subject>Retrospective Studies</subject><subject>Scientific imaging</subject><subject>Substance Abuse Detection</subject><subject>Substance-Related Disorders - diagnosis</subject><subject>Sufentanil</subject><subject>Sufentanil - blood</subject><subject>Sufentanil - urine</subject><subject>Synthetic opioids</subject><subject>Tandem Mass Spectrometry</subject><subject>U-47700</subject><subject>Urine</subject><subject>Young 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detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients</title><author>Jung, Jean ; Kolodziej, Allan ; Pape, Elise ; Bisch, Michael ; Javot, Lucie ; Gibaja, Valérie ; Jouzeau, Jean-Yves ; Scala-Bertola, Julien ; Gambier, Nicolas</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-cbd89f8ff54c07b05f2c3cad25a0ea778e34d8f350d96d8130cdbf65db02b6b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Accuracy</topic><topic>Addictions</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Alfentanil - blood</topic><topic>Alfentanil - urine</topic><topic>Analgesics</topic><topic>Analgesics, Opioid - blood</topic><topic>Analgesics, Opioid - urine</topic><topic>Benzamides - blood</topic><topic>Benzamides - urine</topic><topic>Biological properties</topic><topic>Biological 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fentanyl analogs in urine and whole blood.•Consumption of fentanyl analogs may be underestimated by immunoassay screening.•Importance of urine monitoring of the patients treated with fentanyl and analogs.
Synthetic opioids (SO) associated with the recent alarming increase of deaths and intoxications in United States of America and Europe are not detected by the usual first-line opiates drug screening assays. We developed a liquid chromatography tandem mass spectrometry analytical method for the multiplex detection of 14 fentanyl analogues (2-furanylfentanyl, 4-ANPP, 4-methoxybutyrylfentanyl, acrylfentanyl, alfentanil, carfentanil, despropionyl-2-fluorofentanyl, fentanyl, methoxyacetylfentanyl, norfentanyl, ocfentanil, remifentanil, sufentanil and valerylfentanyl) and U-47700 in whole blood and urine samples. The method was validated according to the requirements of ISO 15189. A simple and fast liquid-liquid extraction (LLE) with De-Tox Tube-A was performed leading to better recovery of molecules in urine than in blood samples. Depending on the compound, the limits of detection (LODs) ranged from 0.01 to 0.10 ng/mL and from 0.02 to 0.05 ng/mL in whole blood and urine, respectively. Calibration curves were linear in the range 0.5–50.0 ng/mL and the limit of quantification (LOQ) ranged from 0.10 to 0.40 ng/mL in blood. Internal quality controls at 1 and 40 ng/mL showed intra-day and between-day precision and accuracy bias below 10% in urine and 15% in blood. The method was applied to the screening of 211 urine samples from patients admitted in emergency or addiction departments. The presence of legal fentanyl analogues in 5 urine samples was justified by their therapeutic use as analgesics. Only one patient was concerned by fentanyl misuse and addiction whereas no illegal SO was detected. This study is not in favor of a huge misuse of SO in the Lorraine region.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>33007729</pmid><doi>10.1016/j.forsciint.2020.110437</doi><orcidid>https://orcid.org/0000-0003-2429-945X</orcidid><orcidid>https://orcid.org/0000-0003-3731-3433</orcidid><orcidid>https://orcid.org/0000-0002-9863-9739</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Forensic science international, 2020-12, Vol.317, p.110437, Article 110437 |
| issn | 0379-0738 1872-6283 |
| language | eng |
| recordid | cdi_hal_primary_oai_HAL_hal_03492148v1 |
| source | MEDLINE; Elsevier ScienceDirect Journals Complete |
| subjects | Accuracy Addictions Adolescent Adult Aged Alfentanil - blood Alfentanil - urine Analgesics Analgesics, Opioid - blood Analgesics, Opioid - urine Benzamides - blood Benzamides - urine Biological properties Biological samples Blood Calibration Child Child, Preschool Chromatography Chromatography, Liquid Drug abuse Drug screening Female Fentanyl Fentanyl - analogs & derivatives Fentanyl - blood Fentanyl - urine Fentanyl analogues Forensic sciences France Furans - blood Furans - urine Heroin HPLC-MS/MS Humanities and Social Sciences Humans Infant Infant, Newborn Limit of Detection Liquid chromatography Liquid-liquid extraction Male Mass spectrometry Mass spectroscopy Middle Aged Misuse Multiplexing Narcotics Neonatal Abstinence Syndrome - diagnosis Nitrogen Opioids Piperidines - blood Piperidines - urine Remifentanil Remifentanil - blood Remifentanil - urine Retrospective Studies Scientific imaging Substance Abuse Detection Substance-Related Disorders - diagnosis Sufentanil Sufentanil - blood Sufentanil - urine Synthetic opioids Tandem Mass Spectrometry U-47700 Urine Young Adult |
| title | Multiplex detection of 14 fentanyl analogues and U-47700 in biological samples: Application to a panel of French hospitalized patients |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-13T11%3A18%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_hal_p&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Multiplex%20detection%20of%2014%20fentanyl%20analogues%20and%20U-47700%20in%20biological%20samples:%20Application%20to%20a%20panel%20of%20French%20hospitalized%20patients&rft.jtitle=Forensic%20science%20international&rft.au=Jung,%20Jean&rft.date=2020-12-01&rft.volume=317&rft.spage=110437&rft.pages=110437-&rft.artnum=110437&rft.issn=0379-0738&rft.eissn=1872-6283&rft_id=info:doi/10.1016/j.forsciint.2020.110437&rft_dat=%3Cproquest_hal_p%3E2479446383%3C/proquest_hal_p%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2479446383&rft_id=info:pmid/33007729&rft_els_id=S0379073820302991&rfr_iscdi=true |