Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum
Introduction: The use of illicitly manufactured synthetic opioids, specifically fentanyl and its analogs, has escalated exponentially in the United States over the last decade. Due to the targeted nature of drug detection methods in clinical laboratories and the ever-evolving list of synthetic opioi...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-11-01
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| Series: | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2667145X22000232 |
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| author | Yu Zhang John C. Halifax Christina Tangsombatvisit Cassandra Yun Shaokun Pang Shirin Hooshfar Alan H.B. Wu Kara L. Lynch |
| author_facet | Yu Zhang John C. Halifax Christina Tangsombatvisit Cassandra Yun Shaokun Pang Shirin Hooshfar Alan H.B. Wu Kara L. Lynch |
| author_sort | Yu Zhang |
| collection | DOAJ |
| description | Introduction: The use of illicitly manufactured synthetic opioids, specifically fentanyl and its analogs, has escalated exponentially in the United States over the last decade. Due to the targeted nature of drug detection methods in clinical laboratories and the ever-evolving list of synthetic opioids of concern, alternative analytical approaches are needed. Methods: Using the fentanyl analog screening (FAS) kit produced by the Centers for Disease Control and Prevention (CDC), we developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) synthetic opioid spectral library and data acquisition method using information dependent acquisition of product ion spectra. Chromatographic retention times, limits of detection and matrix effects, in urine and serum, for the synthetic opioids in the FAS kit (n = 150) were established. All urine and serum specimens sent to a clinical toxicology laboratory for comprehensive drug testing in 2019 (n = 856) and 2021 (n = 878) were analyzed with the FAS LC-HRMS library to determine the prevalence of fentanyl analogs and other synthetic opioids, retrospectively (2019) and prospectively (2021). Results: The limit of detection (LOD) of each opioid ranged from 1 to 10 ng/mL (median, 2.5 ng/mL) in urine and 0.25–2.5 ng/mL (median, 0.5 ng/mL) in serum. Matrix effects ranged from −79 % to 86 % (median, −37 %) for urine, following dilution and direct analysis, and −80 % to 400 % (median, 0 %) for serum, following protein precipitation. The prevalence of fentanyl/fentanyl analogs in serum samples increased slightly from 2019 to 2021 while it remained the same in urine. There were only 2 samples identified that contained a fentanyl analog without the co-occurrence of fentanyl or fentanyl metabolites. Analysis of the established MS/MS spectral library revealed characteristic fragmentation patterns in most fentanyl analogs, which can be used for structure elucidation and drug identification of future analogs. Conclusions: The LC-HRMS method was capable of detecting fentanyl analogs in routine samples sent for comprehensive drug testing. The method can be adapted to accommodate testing needs for the evolving opioid epidemic. |
| first_indexed | 2024-04-11T14:10:58Z |
| format | Article |
| id | doaj.art-129079c7464c4d5dae0fab03b15dd874 |
| institution | Directory Open Access Journal |
| issn | 2667-145X |
| language | English |
| last_indexed | 2024-04-11T14:10:58Z |
| publishDate | 2022-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Mass Spectrometry and Advances in the Clinical Lab |
| spelling | doaj.art-129079c7464c4d5dae0fab03b15dd8742022-12-22T04:19:42ZengElsevierJournal of Mass Spectrometry and Advances in the Clinical Lab2667-145X2022-11-012616Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serumYu Zhang0John C. Halifax1Christina Tangsombatvisit2Cassandra Yun3Shaokun Pang4Shirin Hooshfar5Alan H.B. Wu6Kara L. Lynch7Department of Laboratory Medicine, University of California, San Francisco, and Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, ZSFG Bldg. 5, 2M16 San Francisco, CA 94110, USADepartment of Laboratory Medicine, University of California, San Francisco, and Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, ZSFG Bldg. 5, 2M16 San Francisco, CA 94110, USAUniversity of California, Berkeley, San Francisco, CA 94720, USADepartment of Laboratory Medicine, University of California, San Francisco, and Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, ZSFG Bldg. 5, 2M16 San Francisco, CA 94110, USASCIEX, 1201 Radio Rd, Redwood City, CA 94065, USADepartment of Laboratory Medicine, University of California, San Francisco, and Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, ZSFG Bldg. 5, 2M16 San Francisco, CA 94110, USADepartment of Laboratory Medicine, University of California, San Francisco, and Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, ZSFG Bldg. 5, 2M16 San Francisco, CA 94110, USADepartment of Laboratory Medicine, University of California, San Francisco, and Zuckerberg San Francisco General Hospital, 1001 Potrero Ave, ZSFG Bldg. 5, 2M16 San Francisco, CA 94110, USA; Corresponding author.Introduction: The use of illicitly manufactured synthetic opioids, specifically fentanyl and its analogs, has escalated exponentially in the United States over the last decade. Due to the targeted nature of drug detection methods in clinical laboratories and the ever-evolving list of synthetic opioids of concern, alternative analytical approaches are needed. Methods: Using the fentanyl analog screening (FAS) kit produced by the Centers for Disease Control and Prevention (CDC), we developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) synthetic opioid spectral library and data acquisition method using information dependent acquisition of product ion spectra. Chromatographic retention times, limits of detection and matrix effects, in urine and serum, for the synthetic opioids in the FAS kit (n = 150) were established. All urine and serum specimens sent to a clinical toxicology laboratory for comprehensive drug testing in 2019 (n = 856) and 2021 (n = 878) were analyzed with the FAS LC-HRMS library to determine the prevalence of fentanyl analogs and other synthetic opioids, retrospectively (2019) and prospectively (2021). Results: The limit of detection (LOD) of each opioid ranged from 1 to 10 ng/mL (median, 2.5 ng/mL) in urine and 0.25–2.5 ng/mL (median, 0.5 ng/mL) in serum. Matrix effects ranged from −79 % to 86 % (median, −37 %) for urine, following dilution and direct analysis, and −80 % to 400 % (median, 0 %) for serum, following protein precipitation. The prevalence of fentanyl/fentanyl analogs in serum samples increased slightly from 2019 to 2021 while it remained the same in urine. There were only 2 samples identified that contained a fentanyl analog without the co-occurrence of fentanyl or fentanyl metabolites. Analysis of the established MS/MS spectral library revealed characteristic fragmentation patterns in most fentanyl analogs, which can be used for structure elucidation and drug identification of future analogs. Conclusions: The LC-HRMS method was capable of detecting fentanyl analogs in routine samples sent for comprehensive drug testing. The method can be adapted to accommodate testing needs for the evolving opioid epidemic.http://www.sciencedirect.com/science/article/pii/S2667145X22000232Synthetic opioidsFentanyl analogsLiquid chromatographyHigh resolution mass spectrometry |
| spellingShingle | Yu Zhang John C. Halifax Christina Tangsombatvisit Cassandra Yun Shaokun Pang Shirin Hooshfar Alan H.B. Wu Kara L. Lynch Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum Journal of Mass Spectrometry and Advances in the Clinical Lab Synthetic opioids Fentanyl analogs Liquid chromatography High resolution mass spectrometry |
| title | Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum |
| title_full | Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum |
| title_fullStr | Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum |
| title_full_unstemmed | Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum |
| title_short | Development and application of a High-Resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum |
| title_sort | development and application of a high resolution mass spectrometry method for the detection of fentanyl analogs in urine and serum |
| topic | Synthetic opioids Fentanyl analogs Liquid chromatography High resolution mass spectrometry |
| url | http://www.sciencedirect.com/science/article/pii/S2667145X22000232 |
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