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Forensic Toxicology

Published in:

01-01-2019 | Original Article

Quantification of seven novel synthetic opioids in blood using LC–MS/MS

Authors: Janna Lowry, Michael T. Truver, Madeleine J. Swortwood

Published in: Forensic Toxicology | Issue 1/2019

Abstract

Purpose

The objective of this study was to develop, optimize, and validate a method for the simultaneous quantification of U-47700, AH-7921, U-49900, U-50488, MT-45, W-18, and W-15 in whole blood using liquid chromatography–tandem mass spectrometry (LC–MS/MS).

Methods

Blood samples (500 µL) were fortified with mixed calibrator or quality control (25 µL) and internal standard (10 µL) solutions. Analytes were isolated via a solid-phase extraction procedure. Analysis was performed using an Agilent 1290 Infinity II liquid chromatograph coupled to an Agilent 6470 triple quadrupole mass spectrometer. The method was validated in accordance with Scientific Working Group for Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology and applied to the analysis of postmortem blood specimens.

Results

Lower limits of quantification were 0.25–1 ng/mL and the upper limits of quantification were 100 ng/mL. The coefficients of determination (R²) for the calibration curves were > 0.99. Analytical bias, within-run imprecision, and between-run imprecision were within ± 15%, ≤ 16%, and ≤ 17%, respectively. All analytes were found to be stable at room temperature for 24 h, refrigerated (4 °C) for 72 h, and in the autosampler (4 °C) for 72 h. Authentic blood samples (n = 30) were analyzed using the validated method. Mean (range) U-47700 concentrations were 214 (3.2–1448) ng/mL in 15 cases.

Conclusions

A quantification method for seven synthetic opioids (U-47700, AH-7921, U-49900, U-50488, MT-45, W-18, and W-15) in whole blood was developed, optimized, and validated in accordance with SWGTOX standard practices for method validation in forensic toxicology. This sensitive method was successfully applied to postmortem casework.

O’Donnell JK (2017) Trends in deaths involving heroin and synthetic opioids excluding methadone, and law enforcement drug product reports, by census region—United States, 2006–2015. MMWR Morb Mortal Wkly Rep 66:897–903. https://doi.org/10.15585/mmwr.mm6634a2 CrossRefPubMedPubMedCentral

Seth P (2018) Overdose deaths involving opioids, cocaine, and psychostimulants—United States, 2015–2016. MMWR Morb Mortal Wkly Rep 67:349–358. https://doi.org/10.15585/mmwr.mm6712a1 CrossRefPubMedPubMedCentral

Coopman V, Blanckaert P, Van Parys G, Van Calenbergh S, Cordonnier J (2016) A case of acute intoxication due to combined use of fentanyl and 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700). Forensic Sci Int 266:68–72. https://doi.org/10.1016/j.forsciint.2016.05.001 CrossRefPubMed

Nikolaou P, Katselou M, Papoutsis I, Spiliopoulou C, Athanaselis S (2017) U-47700. An old opioid becomes a recent danger. Forensic Toxicol 35:11–19. https://doi.org/10.1007/s11419-016-0347-4 CrossRef

Dosaka-Akita K, Tortella FC, Holaday JW, Long JB (1993) The kappa opioid agonist U-50,488 H antagonizes respiratory effects of mu opioid receptor agonists in conscious rats. J Pharmacol Exp Ther 264:631–637PubMed

Zawilska JB, Andrzejczak D (2015) Next generation of novel psychoactive substances on the horizon—a complex problem to face. Drug Alcohol Depend 157:1–17. https://doi.org/10.1016/j.drugalcdep.2015.09.030 CrossRefPubMed

Papsun D, Krywanczyk A, Vose JC, Bundock EA, Logan BK (2016) Analysis of MT-45, a novel synthetic opioid, in human whole blood by LC–MS–MS and its identification in a drug-related death. J Anal Toxicol 40:313–317. https://doi.org/10.1093/jat/bkw012 CrossRefPubMed

Lucyk SN, Nelson LS (2017) Novel synthetic opioids: an opioid epidemic within an opioid epidemic. Ann Emerg Med 69:91–93. https://doi.org/10.1016/j.annemergmed.2016.08.445 CrossRefPubMed

Armenian P, Olson A, Anaya A, Kurtz A, Ruegner R, Gerona RR (2017) Fentanyl and a novel synthetic opioid U-47700 masquerading as street “Norco” in Central California: a case report. Ann Emerg Med 69:87–90. https://doi.org/10.1016/j.annemergmed.2016.06.014 CrossRefPubMed

10.

Schneir A, Metushi IG, Sloane C, Benaron DJ, Fitzgerald RL (2016) Near death from a novel synthetic opioid labeled U-47700: emergence of a new opioid class. Clin Toxicol 55:51–54. https://doi.org/10.1080/15563650.2016.1209764 CrossRef

11.

Elliott SP, Brandt SD, Smith C (2016) The first reported fatality associated with the synthetic opioid 3,4-dichloro-N-[2-(dimethylamino)cyclohexyl]-N-methylbenzamide (U-47700) and implications for forensic analysis. Drug Test Anal 8:875–879. https://doi.org/10.1002/dta.1984 CrossRefPubMed

12.

Domanski K, Kleinschmidt KC, Schulte JM, Fleming S, Frazee C, Menendez A, Tavakoli K (2017) Two cases of intoxication with new synthetic opioid, U-47700. Clin Toxicol 55:46–50. https://doi.org/10.1080/15563650.2016.1209763 CrossRef

13.

Jones MJ, Hernandez BS, Janis GC, Stellpflug SJ (2017) A case of U-47700 overdose with laboratory confirmation and metabolite identification. Clin Toxicol 55:55–59. https://doi.org/10.1080/15563650.2016.1209767 CrossRef

14.

Rohrig TP, Miller SA, Baird TR (2017) U-47700: a not so new opioid. J Anal Toxicol 42:e12–e14. https://doi.org/10.1093/jat/bkx081 CrossRef

15.

McIntyre IM, Gary RD, Joseph S, Stabley R (2017) A fatality related to the synthetic opioid U-47700: postmortem concentration distribution. J Anal Toxicol 41:158–160. https://doi.org/10.1093/jat/bkw124 CrossRefPubMed

16.

Ellefsen KN, Taylor EA, Simmons P, Willoughby V, Hall BJ (2017) Multiple drug-toxicity involving novel psychoactive substances, 3-fluorophenmetrazine and U-47700. J Anal Toxicol 41:765–770. https://doi.org/10.1093/jat/bkx060 CrossRefPubMed

17.

Mohr ALA, Friscia M, Papsun D, Kacinko SL, Buzby D, Logan BK (2016) Analysis of novel synthetic opioids U-47700, U-50488 and furanyl fentanyl by LC–MS/MS in postmortem casework. J Anal Toxicol 40:709–717. https://doi.org/10.1093/jat/bkw086 CrossRefPubMed

18.

Karinen R, Tuv SS, Rogde S, Peres MD, Johansen U, Frost J, Vindenes V, Ǿiestad AML (2014) Lethal poisonings with AH-7921 in combination with other substances. Forensic Sci Int 244:e21–e24. https://doi.org/10.1016/j.forsciint.2014.08.013 CrossRefPubMed

19.

Kronstrand R, Thelander G, Lindstedt D, Roman M, Kugelberg FC (2014) Fatal intoxications associated with the designer opioid AH-7921. J Anal Toxicol 38:599–604. https://doi.org/10.1093/jat/bku057 CrossRefPubMed

20.

Vorce SP, Knittel JL, Holler JM, Magluilo J, Levine B, Berran P, Bosy TZ (2014) A fatality involving AH-7921. J Anal Toxicol 38:226–230. https://doi.org/10.1093/jat/bku011 CrossRefPubMed

21.

Fels H, Krueger J, Sachs H, Musshoff F, Graw M, Roider G, Stoever A (2017) Two fatalities associated with synthetic opioids: AH-7921 and MT-45. Forensic Sci Int 277:e30–e35. https://doi.org/10.1016/j.forsciint.2017.04.003 CrossRefPubMed

22.

Morrow JB, Ropero-Miller JD, Catlin ML, Winokur AD, Cadwallader AB, Staymates JL, Williams SR, McGrath JG, Logan BK, McCormick MM, Nolte KB, Gilson TP, Menendez MJ, Goldberger BA (2018) The opioid epidemic: moving toward an integrated, holistic analytical response. J Anal Toxicol. https://doi.org/10.1093/jat/bky049

23.

Shoff EN, Zaney ME, Kahl JH, Hime GW, Boland DM (2017) Qualitative identification of fentanyl analogs and other opioids in postmortem cases by UHPLC-ion trap-MS_n. J Anal Toxicol 41:484–492. https://doi.org/10.1093/jat/bkx041 CrossRefPubMed

24.

Seither J, Reidy L (2017) Confirmation of carfentanil, U-47700 and other synthetic opioids in a human performance case by LC–MS–MS. J Anal Toxicol 41:493–497. https://doi.org/10.1093/jat/bkx049 CrossRefPubMed

25.

Scientific Working Group for Forensic Toxicology (SWGTOX) (2013) Standard practices for method validation in forensic toxicology. J Anal Toxicol 37:452–474. https://doi.org/10.1093/jat/bkt054 CrossRef

26.

Matuszewski B, Constanzer M, Chavez-Eng C (2003) Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC−MS/MS. Anal Chem 75:3019–3030. https://doi.org/10.1021/ac020361s CrossRefPubMed

27.

Truver MT, Swortwood MJ (2018) Quantitative analysis of novel synthetic opioids, morphine and buprenorphine in oral fluid by LC–MS–MS. J Anal Toxicol. https://doi.org/10.1093/jat/bky053

28.

Zaney ME, Shoff EN, Hime GW, Boland DM (2017) Detection of U-47700 in blood and drug paraphernalia from postmortem cases. Society of Forensic Toxicologists Annual Meeting, Boca Raton

29.

Hartman RL, Salamone ME, Nemeth DJ, Gallagher TM, Fellows JS, Kadlec LM, Beno JM (2017) Furanyl fentanyl, butyryl fentanyl, and U-47700 in blood and urine of drivers arrested for driving under the influence of drugs (DUID). Society of Forensic Toxicologists Annual Meeting, Boca Raton

Title: Quantification of seven novel synthetic opioids in blood using LC–MS/MS
Authors: Janna Lowry
Michael T. Truver
Madeleine J. Swortwood
Publication date: 01-01-2019
Publisher: Springer Japan
Published in: Forensic Toxicology / Issue 1/2019
Print ISSN: 1860-8965
Electronic ISSN: 1860-8973
DOI: https://doi.org/10.1007/s11419-018-0458-1

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Quantification of seven novel synthetic opioids in blood using LC–MS/MS

Abstract

Purpose

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

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