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Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high resolution mass spectrometry and findings in forensic toxicology casework.
Drug Test Anal. 2018 Sep; 10(9):1474-1482.DT

Abstract

3-methylfentanyl (3-MF), N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide, has reappeared on the US illicit drug market since its disappearance after a series of overdose deaths in 1988. 3-MF presents an analytical challenge, due to presence of cis and trans stereoisomers, each with different potencies, and ultimately very low concentrations in the blood after use. A method was developed using liquid chromatography-time-of-flight-mass spectrometry for the analysis of (±)-cis-3-MF and (±)-trans-3-MF in blood specimens after solid phase extraction. The linear dynamic range of this method was 0.1-10 ng/mL. Blood samples from 25 postmortem cases and 2 human performance case involving 3-MF were submitted for quantitative analysis. The mean and median concentration for the (±)-cis-3-MF were 0.84 ng/mL (±0.81) and 0.67 ng/mL, respectively, range 0.14-3.43 ng/mL. The resulting (±)-trans-3-MF mean concentration was 0.46 ng/mL (±0.38) and the median concentration was 0.37 ng/mL with a range of 0.11-1.90 ng/mL. The resulting (±)-cis-3-MF and (±)-trans-3-MF concentrations were summed to give the total amount of 3-MF present in the case with the resulting average concentration at 1.28 ng/mL (±1.16), median at 1.01 ng/mL and range 0.18-5.18. As the estimated dose of this compound is approximately 0.1 mg-0.5 mg with the resulting concentrations in the sub-nanogram range, it is necessary for forensic toxicology laboratories to obtain instruments sensitive enough to detect these substances in driving under the influence of drugs and postmortem cases. Quantitation of 3-MF with separation of (±)-cis and (±)-trans-3-MF provides additional detail for more specific toxicological interpretation.

Authors+Show Affiliations

The Center for Forensic Science Research and Education (CFSRE) at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania.NMS Labs, Willow Grove, 19090, Pennsylvania.The Center for Forensic Science Research and Education (CFSRE) at the Fredric Rieders Family Foundation, Willow Grove, Pennsylvania. NMS Labs, Willow Grove, 19090, Pennsylvania.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29801193

Citation

Fogarty, Melissa F., et al. "Analysis of Cis and Trans 3-methylfentanyl By Liquid Chromatography-high Resolution Mass Spectrometry and Findings in Forensic Toxicology Casework." Drug Testing and Analysis, vol. 10, no. 9, 2018, pp. 1474-1482.
Fogarty MF, Papsun DM, Logan BK. Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high resolution mass spectrometry and findings in forensic toxicology casework. Drug Test Anal. 2018;10(9):1474-1482.
Fogarty, M. F., Papsun, D. M., & Logan, B. K. (2018). Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high resolution mass spectrometry and findings in forensic toxicology casework. Drug Testing and Analysis, 10(9), 1474-1482. https://doi.org/10.1002/dta.2414
Fogarty MF, Papsun DM, Logan BK. Analysis of Cis and Trans 3-methylfentanyl By Liquid Chromatography-high Resolution Mass Spectrometry and Findings in Forensic Toxicology Casework. Drug Test Anal. 2018;10(9):1474-1482. PubMed PMID: 29801193.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Analysis of cis and trans 3-methylfentanyl by liquid chromatography-high resolution mass spectrometry and findings in forensic toxicology casework. AU - Fogarty,Melissa F, AU - Papsun,Donna M, AU - Logan,Barry K, Y1 - 2018/06/29/ PY - 2018/02/22/received PY - 2018/05/16/revised PY - 2018/05/18/accepted PY - 2018/5/26/pubmed PY - 2019/3/21/medline PY - 2018/5/26/entrez KW - 3-methylfentanyl KW - LC-QToF KW - high resolution mass spectrometry KW - toxicology SP - 1474 EP - 1482 JF - Drug testing and analysis JO - Drug Test Anal VL - 10 IS - 9 N2 - 3-methylfentanyl (3-MF), N-(3-methyl-1-phenethyl-4-piperidyl)-N-phenyl-propanamide, has reappeared on the US illicit drug market since its disappearance after a series of overdose deaths in 1988. 3-MF presents an analytical challenge, due to presence of cis and trans stereoisomers, each with different potencies, and ultimately very low concentrations in the blood after use. A method was developed using liquid chromatography-time-of-flight-mass spectrometry for the analysis of (±)-cis-3-MF and (±)-trans-3-MF in blood specimens after solid phase extraction. The linear dynamic range of this method was 0.1-10 ng/mL. Blood samples from 25 postmortem cases and 2 human performance case involving 3-MF were submitted for quantitative analysis. The mean and median concentration for the (±)-cis-3-MF were 0.84 ng/mL (±0.81) and 0.67 ng/mL, respectively, range 0.14-3.43 ng/mL. The resulting (±)-trans-3-MF mean concentration was 0.46 ng/mL (±0.38) and the median concentration was 0.37 ng/mL with a range of 0.11-1.90 ng/mL. The resulting (±)-cis-3-MF and (±)-trans-3-MF concentrations were summed to give the total amount of 3-MF present in the case with the resulting average concentration at 1.28 ng/mL (±1.16), median at 1.01 ng/mL and range 0.18-5.18. As the estimated dose of this compound is approximately 0.1 mg-0.5 mg with the resulting concentrations in the sub-nanogram range, it is necessary for forensic toxicology laboratories to obtain instruments sensitive enough to detect these substances in driving under the influence of drugs and postmortem cases. Quantitation of 3-MF with separation of (±)-cis and (±)-trans-3-MF provides additional detail for more specific toxicological interpretation. SN - 1942-7611 UR - https://www.unboundmedicine.com/medline/citation/29801193/Analysis_of_cis_and_trans_3_methylfentanyl_by_liquid_chromatography_high_resolution_mass_spectrometry_and_findings_in_forensic_toxicology_casework_ L2 - https://doi.org/10.1002/dta.2414 DB - PRIME DP - Unbound Medicine ER -