Andrew R. Forero, , , Samuel A. Miller, , , Lilian Valadares Tose, , , Matthew Willetts, , , Mark E. Ridgeway, , , Melvin A. Park, , , Elisa N. Shoff, , and , Francisco Fernandez-Lima*,
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In this study, we present a high-throughput mass spectrometry based method for effective screening of fentanyl analogues with focus on the isomeric separation using commercially available platforms combining liquid chromatography, trapped ion mobility spectrometry, and tandem mass spectrometry (LC-TIMS-q-TOF MS/MS). The proposed analysis allows for effective separation and identification of 250 synthetic opioids based on the isotopic pattern, retention time, mobility profile, and MS/MS pattern. Our approach capitalizes on the advancements incorporating parallel accumulation in the mobility trap followed by sequential fragmentation (PASEF) using collision-induced dissociation on the liquid chromatography time scale. While a single chromatography band is commonly observed for single isomeric analogues, a dual mobility band profile attributed to two protonation sites is commonly observed for most fentanyl analogues. Reference mobility values are reported from single standards with 0.2% RSD collected at high resolution (R<sub>IMS</sub> ≈ 80–120). The added mobility separation resulted in the separation of isomeric compounds without compromising the sensitivity of the LC-q-TOF MS/MS analysis; that is, a good linear dynamic and (R<sup>2</sup> > 0.98) and low limits of detection (LOD) in the 0.08–4 ng/mL range were observed for all synthetic analogues (∼100 analogues can be observed with LOD < 1 ng/mL).</p>","PeriodicalId":672,"journal":{"name":"Journal of the American Society for Mass Spectrometry","volume":"36 10","pages":"2206–2212"},"PeriodicalIF":2.7000,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Complementary Separation of Novel Synthetic Opioids\",\"authors\":\"Andrew R. Forero, , , Samuel A. Miller, , , Lilian Valadares Tose, , , Matthew Willetts, , , Mark E. 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The proposed analysis allows for effective separation and identification of 250 synthetic opioids based on the isotopic pattern, retention time, mobility profile, and MS/MS pattern. Our approach capitalizes on the advancements incorporating parallel accumulation in the mobility trap followed by sequential fragmentation (PASEF) using collision-induced dissociation on the liquid chromatography time scale. While a single chromatography band is commonly observed for single isomeric analogues, a dual mobility band profile attributed to two protonation sites is commonly observed for most fentanyl analogues. Reference mobility values are reported from single standards with 0.2% RSD collected at high resolution (R<sub>IMS</sub> ≈ 80–120). 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Complementary Separation of Novel Synthetic Opioids
The escalating prevalence and diversity of fentanyl analogues poses an immediate concern for the global community. Fentanyl and its analogues are the primary contributors to both fatal and nonfatal overdoses in the United States. The most recent instances of fentanyl-related overdoses have been attributed to the illicit production of fentanyl, characterized by its exceptionally potent nature. In this study, we present a high-throughput mass spectrometry based method for effective screening of fentanyl analogues with focus on the isomeric separation using commercially available platforms combining liquid chromatography, trapped ion mobility spectrometry, and tandem mass spectrometry (LC-TIMS-q-TOF MS/MS). The proposed analysis allows for effective separation and identification of 250 synthetic opioids based on the isotopic pattern, retention time, mobility profile, and MS/MS pattern. Our approach capitalizes on the advancements incorporating parallel accumulation in the mobility trap followed by sequential fragmentation (PASEF) using collision-induced dissociation on the liquid chromatography time scale. While a single chromatography band is commonly observed for single isomeric analogues, a dual mobility band profile attributed to two protonation sites is commonly observed for most fentanyl analogues. Reference mobility values are reported from single standards with 0.2% RSD collected at high resolution (RIMS ≈ 80–120). The added mobility separation resulted in the separation of isomeric compounds without compromising the sensitivity of the LC-q-TOF MS/MS analysis; that is, a good linear dynamic and (R2 > 0.98) and low limits of detection (LOD) in the 0.08–4 ng/mL range were observed for all synthetic analogues (∼100 analogues can be observed with LOD < 1 ng/mL).
期刊介绍:
The Journal of the American Society for Mass Spectrometry presents research papers covering all aspects of mass spectrometry, incorporating coverage of fields of scientific inquiry in which mass spectrometry can play a role.
Comprehensive in scope, the journal publishes papers on both fundamentals and applications of mass spectrometry. Fundamental subjects include instrumentation principles, design, and demonstration, structures and chemical properties of gas-phase ions, studies of thermodynamic properties, ion spectroscopy, chemical kinetics, mechanisms of ionization, theories of ion fragmentation, cluster ions, and potential energy surfaces. In addition to full papers, the journal offers Communications, Application Notes, and Accounts and Perspectives