Brorphine—Investigation and quantitation of a new potent synthetic opioid in forensic toxicology casework using liquid chromatography‐mass spectrometr y
Abstract
New synthetic opioids continue to appear as novel psychoactive substances (NPS) on illicit drug markets. Isotonitazene emerged in mid‐2019, becoming the most prevalent NPS opioid in the United States within a few months. Notification by the Drug Enforcement Administration of its intent to schedule isotonitazene in mid‐2020 led to its decline in popularity and replacement with a new NPS opioid: brorphine. Brorphine is a potent synthetic opioid, but little information was previously available regarding its toxicity or involvement in impairment and death. Our laboratory developed an assay for the identification and quantitative confirmation of brorphine using standard addition. Quantitative analysis was performed using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). In vitro and in vivo metabolism studies were performed using pooled human liver microsomes and authentic biological specimens, respectively, with analysis by liquid chromatography quadrupole time‐of‐flight mass spectrometry (LC‐QTOF‐MS). Brorphine was confirmed in 20 authentic forensic cases, commonly found in combination with fentanyl (100%) and flualprazolam (80%). The average concentration of brorphine in blood was 2.5 ± 3.1 ng/mL (median: 1.1 ng/mL, range: 0.1–10 ng/mL). The average concentration of brorphine in urine was 4.6 ± 7.6 ng/mL (median: 1.6 ng/mL, range: 0.2–23 ng/mL). The majority of cases originated from Midwestern states. Metabolism was verified to included N‐dealkylation and hydroxylation. Detailed case histories and autopsy findings are presented herein. The prevalence of brorphine continues to increase in the United States. Forensic scientists should remain aware of the ongoing emergence of new opioids, especially those outside a standard scope of toxicology testing.
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Brorphine appeared on recreational drug markets around the globe from 2019 onwards and was also identified in (postmortem) toxicology samples.
“Notably, brorphine appeared on recreational drug markets around the globe from 2019 onwards (Krotulski et al., 2020b; Ujváry et al., 2021; Vandeputte et al., 2022a; Verougstraete et al., 2020) and was also identified in (postmortem) toxicology samples (Krotulski et al., 2020a; Verougstraete et al., 2020; Vohra et al., 2021).”
From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Krotulski et al., 2020b
More than 60 fatal and non-fatal case reports involving brorphine have been described.
“More than 60 fatal and non-fatal case reports involving brorphine have been described (Grafinger et al., 2021; Krotulski et al., 2020a; Razinger et al., 2021; Verougstraete et al., 2020; Vohra et al., 2021; World Health Organization, 2021), underscoring the risks associated with its use.”
From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Krotulski et al., 2020a
Brorphine is known to undergo N-dealkylation and hydroxylation in humans, with the N-dealkylated metabolite expected to be a common metabolite for the different analogues studied here.
“Brorphine is known to undergo N -dealkylation and hydroxylation in humans (Grafinger et al., 2021; Krotulski et al., 2020a), with the N -dealkylated metabolite expected to be a common metabolite for the different analogues studied here (Krotulski et al., 2020a).”
From Elucidating the harm potential of brorphine analogues as new synthetic opioids: Synthesis, in vitro, and in vivo characterization (2024) · cites this paper as Krotulski et al., 2020a
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Self-citationThe Rise and Fall of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Firmament
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- Authors
- Krotulski, A. J., Papsun, D. M., Noble, C., Kacinko, S. L., & Logan, B. K.
- Affiliations
- Fredric Rieders Family Foundation (US)
- NMS Labs Horsham PA 19044 USA
- Corresponding author
- Krotulski, Alex J.
- Venue
- Journal of Forensic Sciences
- Publisher
- Wiley
- Published
- 2020-11-17
- Volume
- 66
- Issue
- 2
- Pages
- 664-676
- ISSN
- 0022-1198 (ISSN-L)
- 1556-4029
- OpenAlex
- W3100180555
- Cited by
- 47
- References
- 2
- Citations by year
- 2026: 6 · 2025: 5 · 2024: 5 · 2023: 9 · 2022: 10 · 2021: 12
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Forensic Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Health Sciences › Medicine › Emergency Medicine › Poisoning and overdose treatments
- Keywords
- synthetic opioids, new psychoactive substances, isotonitazene, forensic toxicology, drug metabolism, N-dealkylation, hydroxylation, fentanyl, postmortem toxicology
- MeSH terms
- Synthetic Drugs, Adult, Analgesics, Opioid, Biotransformation, Chromatography, Liquid, Female, Humans, Imidazoles, Male, Middle Aged, Piperidines, Illicit Drugs, Molecular Structure, Forensic Toxicology, Tandem Mass Spectrometry
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