Development and validation of a combined selected ion monitoring‐scan GC ‐ EI ‐ MS method for nitazene analogs
Abstract
Novel synthetic opioids (NSOs) emerged during the third wave of the opioid epidemic, which has resulted in countless overdose deaths. Although fentanyl and fentanyl analogs are the most common NSOs, changing legislation in China and the United States led to the emergence of another class of NSOs, known as nitazene analogs. Nitazene analogs are very potent, and given their increasing prevalence in seized drug casework, it is imperative that seized drug laboratories have sufficient methods to identify nitazene analogs. This study developed a combined selected ion monitoring (SIM)-scan method to identify 20 nitazene analogs using gas chromatography-electron ionization-mass spectrometry (GC-EI-MS). The method was evaluated in terms of the limit of detection (LOD), carryover, selectivity, repeatability, reproducibility, and processed sample stability. The LOD for the targeted nitazene analogs ranged from 5 to 10 ppm due to increased sensitivity through SIM acquisition. No carryover was observed, and all nitazene analogs could be differentiated from other analogs and common interferences. The repeatability and reproducibility of the method were demonstrated qualitatively. All nitazene analogs were stable at room temperature for at least 24 hours. When applied to the analysis of blind simulant samples, 33 out of 35 samples were correctly identified, with the two misidentifications being due to ion ratios outside of tolerance. Likewise, two authentic nitazene analog casework samples were also correctly identified. The validated SIM-scan method provides a potential solution to identify low concentration nitazene analogs in seized drug casework that might otherwise be missed using routine GC-MS full scan acquisition.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Older gas chromatography-mass spectrometry methods frequently lack the necessary sensitivity for nitazenes, often missing them in casework.
“Furthermore, older gas chromatography–mass spectrometry methods also frequently lack the necessary sensitivity for nitazenes, often missing them in casework [50,51,52].”
From Nitazenes: The Emergence of a Potent Synthetic Opioid Threat (2025) · cites this paper as [51]
Cites
Drug Overdose Deaths in the United States, 1999–2020
Hedegaard, H., Miniño, A., Spencer, M. R., & Warner, M. (2021) · doi:10.15620/cdc:112340 · Cited by 1,283 · see citing works
The triple wave epidemic: Supply and demand drivers of the US opioid overdose crisis
Ciccarone, D. (2019) · International Journal of Drug Policy · doi:10.1016/j.drugpo.2019.01.010 · Cited by 677 · see citing works
Gladden, R. M., Martínez, P. D., & Seth, P. (2016) · MMWR Morbidity and Mortality Weekly Report · doi:10.15585/mmwr.mm6533a2 · Cited by 426 · see citing works
Mass Spectrometry, Review of the Basics: Electrospray, MALDI, and Commonly Used Mass Analyzers
El‐Aneed, A., Cohen, A., & Banoub, J. H. (2009) · Applied Spectroscopy Reviews · doi:10.1080/05704920902717872 · Cited by 398 · see citing works
Gillis, A., Gondin, A. B., Kliewer, A., Sanchez, J., Lim, H. D., Alamein, C., Manandhar, P., Santiago, M., Fritzwanker, S., Schmiedel, F., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aaz3140 · Cited by 365 · see citing works
Raman spectroscopy in forensic analysis: identification of cocaine and other illegal drugs of abuse
Penido, C. A. F. D. O., Pacheco, M. T. T., Lednev, I. K., & Silveira, L. (2016) · Journal of Raman Spectroscopy · doi:10.1002/jrs.4864 · Cited by 202 · see citing works
Vandeputte, M. M., Van Uytfanghe, K., Layle, N. K., St. Germaine, D. M., Iula, D. M., & Stove, C. P. (2021) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.1c00064 · Cited by 161 · see citing works
Isotonitazene Quantitation and Metabolite Discovery in Authentic Forensic Casework
Krotulski, A. J., Papsun, D. M., Kacinko, S. L., & Logan, B. K. (2020) · Journal of Analytical Toxicology · doi:10.1093/jat/bkaa016 · Cited by 146 · see citing works
Jenkins, R. A. (2021) · Preventive Medicine · doi:10.1016/j.ypmed.2021.106541 · Cited by 129 · see citing works
Blanckaert, P., Cannaert, A., Van Uytfanghe, K., Hulpia, F., Deconinck, E., Van Calenbergh, S., & Stove, C. (2020) · Drug Testing and Analysis · doi:10.1002/dta.2738 · Cited by 116 · see citing works
Walton, S. E., Krotulski, A. J., & Logan, B. K. (2022) · Journal of Analytical Toxicology · doi:10.1093/jat/bkab117 · Cited by 92 · see citing works
Mueller, F., Bogdal, C., Pfeiffer, B., Andrello, L., Ceschi, A., Thomas, A., & Grata, E. (2021) · Forensic Science International · doi:10.1016/j.forsciint.2021.110686 · Cited by 82 · see citing works
Old Drugs and New Challenges: A Narrative Review of Nitazenes
Pergolizzi Jr, J., Raffa, R., LeQuang, J. A. K., Breve, F., & Varrassi, G. (2023) · Cureus · doi:10.7759/cureus.40736 · Cited by 81 · see citing works
Vandeputte, M. M., Krotulski, A. J., Walther, D., Glatfelter, G. C., Papsun, D., Walton, S. E., Logan, B. K., Baumann, M. H., & Stove, C. P. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03276-4 · Cited by 80 · see citing works
The Rise and Fall of Isotonitazene and Brorphine: Two Recent Stars in the Synthetic Opioid Firmament
Vandeputte, M. M., Krotulski, A. J., Papsun, D. M., Logan, B. K., & Stove, C. P. (2022) · Journal of Analytical Toxicology · doi:10.1093/jat/bkab082 · Cited by 71 · see citing works
Creation and Release of an Updated NIST DART-MS Forensics Database
Sisco, E., Moorthy, A. S., & Watt, L. M. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.0c00416 · Cited by 60 · see citing works
The use of presumptive color tests for new psychoactive substances
Cuypers, E., Bonneure, A., & Tytgat, J. (2015) · Drug Testing and Analysis · doi:10.1002/dta.1847 · Cited by 56 · see citing works
Rossi, S. S., Bermejo, A. M., de la Torre, X., & Botrè, F. (2010) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-010-4471-4 · Cited by 48 · see citing works
Penido, C. A. F. D. O., Pacheco, M. T. T., Novotny, E. H., Lednev, I. K., & Silveira, L. (2017) · Journal of Raman Spectroscopy · doi:10.1002/jrs.5231 · Cited by 46 · see citing works
Vandeputte, M. M., Verougstraete, N., Walther, D., Glatfelter, G. C., Malfliet, J., Baumann, M. H., Verstraete, A. G., & Stove, C. P. (2022) · Archives of Toxicology · doi:10.1007/s00204-022-03294-2 · Cited by 44 · see citing works
Control of fentanyl-related substances in China
Bao, Y., Meng, S., Shi, J., & Lü, L. (2019) · The Lancet Psychiatry · doi:10.1016/s2215-0366(19)30218-4 · Cited by 42 · see citing works
National Forensic Laboratory Information System
Pressley, D., Moore, K., Weimer, B., McDonald, H. S., & Ropero‐Miller, J. D. (2018) · Forensic science review · Cited by 38 · see citing works
Ververi, C., Galletto, M., Massano, M., Alladio, E., Vincenti, M., & Salomone, A. (2024) · Journal of Pharmaceutical and Biomedical Analysis · doi:10.1016/j.jpba.2024.115975 · Cited by 34 · see citing works
Wallace, M. A. G., Pleil, J. D., Menteşe, S., Oliver, K. D., Whitaker, D. A., & Fent, K. W. (2017) · Journal of Chromatography A · doi:10.1016/j.chroma.2017.07.082 · Cited by 32 · see citing works
Kelly, K., & Bell, S. (2017) · Forensic Chemistry · doi:10.1016/j.forc.2017.11.002 · Cited by 31 · see citing works
A New Library-Search Algorithm for Mixture Analysis Using DART-MS
Moorthy, A. S., & Sisco, E. (2021) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.1c00097 · Cited by 31 · see citing works
Vandeputte, M. M., Persson, M., Walther, D. M., Vikingsson, S., Kronstrand, R., Baumann, M. H., Gréen, H., & Stove, C. P. (2022) · Archives of Toxicology · doi:10.1007/s00204-021-03207-9 · Cited by 25 · see citing works
Feeney, W., Moorthy, A. S., & Sisco, E. (2022) · Forensic Chemistry · doi:10.1016/j.forc.2022.100459 · Cited by 24 · see citing works
Forensic seized drug analysis: Current challenges and emerging analytical solutions
Joshi, M., & Sisco, E. (2023) · Wiley Interdisciplinary Reviews Forensic Science · doi:10.1002/wfs2.1486 · Cited by 24 · see citing works
Updates to the Inverted Library Search Algorithm for Mixture Analysis
Moorthy, A. S., Tennyson, S. S., & Sisco, E. (2022) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.2c00090 · Cited by 23 · see citing works
Presumptive and Confirmatory Drug Tests
Anderson, C. M. (2005) · Journal of Chemical Education · doi:10.1021/ed082p1809 · Cited by 20 · see citing works
Structural Characterization of Nitazene Analogs Using Electron Ionization-Mass Spectrometry (EI-MS)
Hardwick, E. K., & Tyler Davidson, J. (2024) · Forensic Chemistry · doi:10.1016/j.forc.2024.100605 · Cited by 20 · see citing works
Self-citationSisco, E., Burns, A., & Moorthy, A. S. (2021) · Journal of Forensic Sciences · doi:10.1111/1556-4029.14877 · Cited by 18 · see citing works
Differentiation of hemp from marijuana using a qualitative decision-point assay
Cheng, Y., & Kerrigan, S. (2023) · Forensic Chemistry · doi:10.1016/j.forc.2023.100541 · Cited by 13 · see citing works
Practice for Validation of Seized-Drug Analytical Methods
E30 Committee (2013) · doi:10.1520/e2549 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nitazenes: The Emergence of a Potent Synthetic Opioid Threat
Pereira, J. R. P., Quintas, A., & Neng, N. R. (2025) · Molecules · doi:10.3390/molecules30193890 · Cited by 21 · see citing works
Analytical approaches for the identification and quantitation of nitazenes: a review
Mandrioli, R., Protti, M., Lecce, R. D., & Mercolini, L. (2025) · Journal of Chromatography Open · doi:10.1016/j.jcoa.2025.100305 · Cited by 7 · see citing works
Zhang, M., Chen, H., Tang, Y., Lin, M., Xiang, P., Yan, H. F., & Zhao, J. (2025) · Journal of the American Society for Mass Spectrometry · doi:10.1021/jasms.5c00081 · Cited by 3 · see citing works
The Nitazene Era: A Critical Turning Point in the Synthetic Opioid Crisis Beyond Fentanyl
Dow, L. F., Abisogun, A. A., Berida, T. I., Krishnan, S. C., Rathnayake, U., & Lindsley, C. W. (2026) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6c00696 · Cited by 2 · see citing works
Opioid-like designer drugs: A practical review of detection, confirmation and interpretation
Protti, M., Iattoni, C. P., Santos, H. M., Lodeiro, C., Capelo, J. L., Lecce, R. D., Mandrioli, R., & Mercolini, L. (2026) · Journal of Pharmaceutical and Biomedical Analysis Open · doi:10.1016/j.jpbao.2026.100112
Determination of nitazenes in postmortem casework and their prevalence in the State of Maryland
Fagiola, M., & Phipps, R. (2026) · Journal of Analytical Toxicology · doi:10.1093/jat/bkag031
- Authors
- Phelps, C., Hardwick, E. K., Couch, A. N., & Davidson, J. T.
- Affiliations
- Sam Houston State University (US)
- Corresponding author
- Davidson, J. Tyler
- Venue
- Journal of Forensic Sciences
- Publisher
- Wiley
- Published
- 2025-05-19
- Volume
- 70
- Issue
- 5
- Pages
- 1949-1962
- ISSN
- 0022-1198 (ISSN-L)
- 1556-4029
- OpenAlex
- W4410523062
- Cited by
- 6
- References
- 35
- Citations by year
- 2026: 3 · 2025: 3
- FWCI
- 3.08
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Journal of Forensic Sciences (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Commerce (60NANB23D092)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Forensic Toxicology and Drug Analysis
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Opioid Use Disorder Treatment
- Keywords
- synthetic opioids, selected ion monitoring, carryover, sample stability
- MeSH terms
- Analgesics, Opioid, Humans, Gas Chromatography-Mass Spectrometry, Thiazoles, Designer Drugs, Reproducibility of Results, Forensic Toxicology, Limit of Detection
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
