Rapid identification of cyclopropyl fentanyl/crotonyl fentanyl in clinical urine specimens: A case study of clinical laboratory collaboration in Canada

Palaty, Jan; Konforte, Danijela; Karakosta, Theano D.; Wong, Ernest; Stefan, Cristiana

doi:10.1016/j.clinbiochem.2018.01.013

Cited by 19 publications

(19 citation statements)

References 3 publications

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“…Prior to shipment, 10 μL of a 10% ( w / v ) aqueous solution of mannitol was added to the cartridges and dried prior to the addition of 10 μL of an internal standard cocktail, allowing the cartridge to dry at room temperature (Indianapolis, IN, USA). Following air shipment of the cartridges to the remote testing laboratory (Vancouver Island, BC, Canada), 10 μL anonymous urine samples (previously analyzed by HPLC/MS for NPS, procedures used published elsewhere) were deposited on the preloaded cartridges, which were then returned by air shipment for PS‐MS measurements. For clarity, the anonymous urine samples were originally submitted to LifeLabs for standard drug testing, including fentanyl and its analogs.…”

Section: Methodssupporting

confidence: 87%

“…Methamphetamine, 3,4‐methylenedioxymethamphetamine, 3,4‐methylenedioxy‐ N ‐ethylamphetamine and cocaine were the most common DOA identified in these urine samples, in addition to fentanyl and norfentanyl. Cyclopropylfentanyl, a “new” IMF, was detected in several samples, with only one sample testing positive for norcarfentanil. Based upon comparison with signals observed for neat analytical standards, acetylfentanyl, acrylfentanyl, carfentanil, desmethyl U‐47700, and sufentanil were not detected in any of the urine samples analyzed.…”

Section: Resultsmentioning

confidence: 99%

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Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry

Kennedy

Palaty²,

Gill

et al. 2018

Rapid Comm Mass Spectrometry

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Section: Methodssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 99%

Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry

Kennedy

Palaty²,

Gill

et al. 2018

Rapid Comm Mass Spectrometry

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“…CycP‐F presents the same empirical formula (C 23 H 28 N 2 O) as another fentanyl analogue, crotonylfentanyl (Cro‐F) . Analytical differentiation of these compounds has proven difficult .…”

Section: Introductionmentioning

confidence: 99%

“…As such, it has been recommended that findings be reported as CycP‐F/Cro‐F . The same approach will be taken in this study as has been reported previously; while the CycP‐F notation will be utilised, identification in biological samples will represent CycP‐F/Cro‐F. The metabolism of Cro‐F has not been reported.…”

Section: Introductionmentioning

confidence: 99%

“…CycP-F presents the same empirical formula (C 23 H 28 N 2 O) as another fentanyl analogue, crotonylfentanyl (Cro-F). 16,17 Analytical differentiation of these compounds has proven difficult. 17 One group has reported the differention of CycP-F and two isomers of Cro-F utilising GC-MS. 18 However, spectrally only minor differences in ion ratios were observed between CycP-F and the two Cro-F isomers, and additional analysis with FTIR or NMR was recommended to support identification.…”

Section: Introductionmentioning

confidence: 99%

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In vitro metabolism of the novel synthetic opioid agonist cyclopropylfentanyl and subsequent confirmation in authentic human samples using liquid chromatography‐high resolution mass spectrometry

Cutler¹,

Hudson²

2019

Drug Testing and Analysis

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Novel synthetic opioids (NSOs) are a class of novel psychoactive substances (NPS) that are growing in popularity and presenting a significant public health risk. Included in this class are derivatives of the highly potent analgesic, fentanyl. Cyclopropylfentanyl (CycP‐F) was first reported to the EU Early Warning System in August 2017, and was subsequently linked to more than 100 deaths in the US alone. Limited pharmacological, pharmacokinetic or toxicological data is available for many emerging NSOs; however we can expect novel fentanyl analogues to present limited detection windows, short onset, narrow therapeutic indices and the potential for very high potency. Knowledge of the metabolism of these drugs is essential for the identification of analytical targets for their detection. Therefore in vitro metabolites of CycP‐F were produced using human liver microsomal incubations. Metabolites formed were elucidated using liquid chromatography‐high resolution accurate mass analysis (LC‐HRAM). Identified metabolites were added to our accurate mass screening database for NPS which was utilised for subsequent screening analysis. CycP‐F and metabolites were identified in two human blood case samples. Eleven metabolites were identified in vitro, with the major metabolites produced via N‐dealkylation, monohydroxylation and N‐oxidation. Analysis of the positive case samples identified four in vivo metabolites, all of which were observed in vitro. The major metabolite identified in vitro and in vivo was the N‐dealkylated nor‐metabolite; two further mono‐hydroxylated and one dihydroxylated metabolite were detected in vivo.

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The analytical challenges of cyclopropylfentanyl and crotonylfentanyl: An approach for toxicological analysis

Maher¹,

Elliott²,

George³

2018

Drug Testing and Analysis

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New psychoactive substances (NPS) are increasingly being seen in forensic casework globally and encompass a number of types of drugs including "designer opioids", especially fentanyl analogues, which are of particular concern due to their high potency and significant risk of toxicity. They are often sold as heroin or mixed with other illicit drugs and therefore users may be unaware they are taking such hazardous compounds. Two fentanyl analogues that have recently been detected are cyclopropylfentanyl and crotonylfentanyl. In order to accurately determine the prevalence of such compounds in clinical and forensic casework, including potential toxicity, they need to be correctly identified using definitive and defensible techniques. Cyclopropylfentanyl and crotonylfentanyl are structural isomers, and it has previously been highlighted that these 2 compounds are analytically difficult to specifically identify owing to their similarity in structure and chromatographic behaviour. To further investigate in an attempt to overcome this problem, analysis of certified reference material using high performance liquid chromatography with diode array UV detection (HPLC-DAD), liquid chromatography-tandem mass spectrometry (LC-MS/MS), and liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QToF-MS) has been performed. Whilst the compounds were shown to have an identical mass-spectral fragmentation pattern, they had different UV spectra. This was coupled with a discernible difference in retention time with the HPLC conditions applied, allowing differentiation of the 2 compounds. Using this approach, cyclopropylfentanyl was positively identified and subsequently quantified in 4 fatalities with the exclusion of crotonylfentanyl.

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Rapid identification of cyclopropyl fentanyl/crotonyl fentanyl in clinical urine specimens: A case study of clinical laboratory collaboration in Canada

Cited by 19 publications

References 3 publications

Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry

Rapid analysis of fentanyls and other novel psychoactive substances in substance use disorder patient urine using paper spray mass spectrometry

In vitro metabolism of the novel synthetic opioid agonist cyclopropylfentanyl and subsequent confirmation in authentic human samples using liquid chromatography‐high resolution mass spectrometry

The analytical challenges of cyclopropylfentanyl and crotonylfentanyl: An approach for toxicological analysis

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