Analysis of cis and trans 3‐methylfentanyl by liquid chromatography–high resolution mass spectrometry and findings in forensic toxicology casework. Issue 9 (29th June 2018)

• Record Type: Journal Article
• Authors: Fogarty, Melissa F.; Papsun, Donna M.; Logan, Barry K.
• Is Part Of: Drug testing and analysis. Volume 10:Issue 9(2018)
• Page Start: 1474
• Page End: 1482
• Publication Date: 2018-06-29
• Subjects: 3‐methylfentanyl -- high resolution mass spectrometry -- LC–QToF -- toxicology; Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.2414
• Languages: English
• ISSNs: 1942-7603

Abstract

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. Abstract : A method was developed and validated for the detection of cis and trans 3‐methylfentanyl in post‐mortem and human performance toxicological cases using liquid chromatography–quadrupole time of flight instrumentation.