Qualitative studies on the metabolism and the toxicological detection of the fentanyl-derived designer drugs 3-methylfentanyl and isofentanyl in rats using liquid chromatography–linear ion trap–mass spectrometry (LC-MSn)

@article{Meyer2011QualitativeSO,
  title={Qualitative studies on the metabolism and the toxicological detection of the fentanyl-derived designer drugs 3-methylfentanyl and isofentanyl in rats using liquid chromatography–linear ion trap–mass spectrometry (LC-MSn)},
  author={Markus R. Meyer and Julia Dinger and Andrea E. Schwaninger and Dirk K. Wissenbach and Josef Zapp and Giselher Fritschi and Hans H. Maurer},
  journal={Analytical and Bioanalytical Chemistry},
  year={2011},
  volume={402},
  pages={1249-1255}
}
The opioid 3-methylfentanyl, a designer drug of the fentanyl type, was scheduled by the Controlled Substance Act due to its high potency and abuse potential. To overcome this regulation, isofentanyl, another designer fentanyl, was synthesized in a clandestine laboratory and seized by the German police. The aims of the presented study were to identify the phase I and phase II metabolites of 3-methylfentanyl and isofentanyl in rat urine, to identify the cytochrome P450 (CYP) isoenzymes involved… 
View on Springer
ncbi.nlm.nih.gov
36 Citations
Highly Influential Citations
1
Background Citations
2
Methods Citations
3
Results Citations
1

36 Citations

Studies on the metabolism of the fentanyl-derived designer drug butyrfentanyl in human in vitro liver preparations and authentic human samples using liquid chromatography-high resolution mass spectrometry (LC-HRMS).

In vitro and in vivo phase I and phase II metabolites of butyrfentanyl were elucidated combining liquid chromatography with a qTOF high resolution mass spectrometer and Butyrf fentanyl was shown to undergo extensive metabolism.

In vitro characterization of potential CYP- and UGT-derived metabolites of the psychoactive drug 25B-NBOMe using LC-high resolution MS.

Twenty-one metabolites, consisting of 12 CYP-derived and 9 UGT-derived metabolites, were identified and O-Desmethyl metabolites were the most abundant compounds after the phase I process, which appears to be in accordance with data from previously published NBOMe-intoxication case reports.

2-Methiopropamine, a thiophene analogue of methamphetamine: studies on its metabolism and detectability in the rat and human using GC-MS and LC-(HR)-MS techniques

Following the administration of a typical user’s dose, 2-MPA and its metabolites were identified in rat urine using the authors’ GC-MS and the LC-MSn screening approaches and the following major metabolic pathways were proposed: N-demethylation, hydroxylation at the side chain and at the thiophene ring, and combination of these transformations followed by glucuronidation and/or sulfation.

Qualitative metabolism assessment and toxicological detection of xylazine, a veterinary tranquilizer and drug of abuse, in rat and human urine using GC–MS, LC–MSn, and LC–HR-MSn

It should be possible to monitor application of xylazine assuming similar toxicokinetics in humans, and mainly the hydroxy metabolites were detected using the authors’ standard urine screening approaches by GC–MS and LC–MSn.

Toxicokinetic studies and analytical toxicology of the new synthetic opioids cyclopentanoyl-fentanyl and tetrahydrofuranoyl-fentanyl.

Investigation of the in vitro toxicokinetics and in vivo analytical toxicology of CP-F and THF-F by means of liquid chromatography high-resolution tandem mass spectrometry showed that neither the parent compounds nor their metabolites were detectable in rat urine using LC-HRMS/MS SUSA, however, a more sophisticated analytical strategy was successfully applied.

Discovering the major metabolites of the three novel fentanyl analogues 3-methylcrotonylfentanyl, furanylbenzylfentanyl, and 4-fluorocyclopropylbenzylfentanyl for forensic case work

The structures of the major metabolites of the three novel fentanyl analogues 3-methylcrotonylfentanyl, FBF, and 4-FCBF are discovered and elucidated which could be used as markers to confirm intake of these compounds in forensic case work.

The in vivo and in vitro metabolism and the detectability in urine of 3',4'-methylenedioxy-alpha-pyrrolidinobutyrophenone (MDPBP), a new pyrrolidinophenone-type designer drug, studied by GC-MS and LC-MS(n.).

In rat urine after a typical user's dose as well as in human urine, mainly the metabolites could be detected using the authors' SUSA by GC-MS and LC-MS(n) .

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

In vitro metabolites of CycP-F were produced using human liver microsomal incubations and identified metabolites were added to the accurate mass screening database for NPS which was utilised for subsequent screening analysis.

Unique Structural/Stereo-Isomer and Isobar Analysis of Novel Fentanyl Analogues in Postmortem and DUID Whole Blood by UHPLC-MS-MS.

To the authors' knowledge, FG2 is the first published method that achieved baseline resolution of the nine structural/stereo isomers and one isobar by ultra-high performance liquid chromatography-MS-MS and provided quantitative validation data for nine compounds.

In Vitro and In Vivo Metabolite Identification Studies for the New Synthetic Opioids Acetylfentanyl, Acrylfentanyl, Furanylfentanyl, and 4-Fluoro-Isobutyrylfentanyl

In vitro and in vivo metabolite identification studies for new fentanyl analogs matched the in vivo findings well, showing identical biotransformations in each system, and suggest the following specific and abundant metabolites as analytical targets in urine.

References

SHOWING 1-10 OF 17 REFERENCES

Studies on the metabolism of the α-pyrrolidinophenone designer drug methylenedioxy-pyrovalerone (MDPV) in rat and human urine and human liver microsomes using GC-MS and LC-high-resolution MS and its detectability in urine by GC-MS.

The aim of the presented work was to identify the phase I and II metabolites of MDPV and the human cytochrome-P450 (CYP) isoenzymes responsible for its main metabolic step(s), and the detectability of M DPV in urine by the authors' systematic toxicological analysis (STA).

A comprehensive LC-MS-based quantitative analysis of fentanyl-like drugs in plasma and urine.

A fully validated analytical method for the determination of these fentanyl-type compounds in plasma and urine is presented, consisting of a liquid-liquid extraction followed by a LC-MS/MS analysis using electrospray ionisation in the positive ionisation mode.

Studies on 1-(2-Phenethyl)-4-(N-Propionylanilino)Piperidine (Fentanyl) and Its Related Compounds: Novel Metabolites in Rat Urine Following Injection of α-Methylfentanyl, One of the Most Abused Typical Designer Drugs

Four novel metabolites, which reflect the original structure of α-methylfentanyl, were identified in rat urine, and were identified by comparisons of their retention times and mass spectra obtained by gas chromatography-mass spectrometry (GC/MS) and mass chromatography of mono- and di-hydroxy α- methylf fentanyl with those of the synthesized authentic compounds.

Enantioselectivity in the methylation of the catecholic phase I metabolites of methylenedioxy designer drugs and their capability to inhibit catechol-O-methyltransferase-catalyzed dopamine 3-methylation.

Elimination of the catecholamine metabolites of MDMA, MDEA, and MBDB was shown to be enantioselective and might therefore contribute to the different pharmacokinetic properties observed for both enantiomers.

Metabolism of fentanyl, a synthetic opioid analgesic, by human liver microsomes. Role of CYP3A4.

  • D. FeiermanJ. Lasker
  • Biology, Chemistry
    Drug metabolism and disposition: the biological fate of chemicals
  • 1996
It is indicated that CYP3A4 is the major catalyst involved in fentanyl oxidation to norfentanyl in human liver, which could lead to marked perturbations in fentanyl disposition and, hence, analgesic response.

Drugs of abuse screening in urine as part of a metabolite-based LC-MSn screening concept

The presented LC-MSn method complements the well-established gas chromatography-mass spectroscopy procedure in the authors’ laboratory and could be used for drug screening in clinical and forensic toxicology and in doping control.

Development of the first metabolite-based LC-MSn urine drug screening procedure-exemplified for antidepressants

The presentedLC-MSn method complements established GC-MS or LC-MS procedures in the authors’ lab and allowed detecting unknown compounds based on known fragment structures and confirms the body passage.

Studies on 1-(2-phenethyl)-4-(N-propionylanilino)piperidine (fentanyl) and its related compounds. VI. Structure-analgesic activity relationship for fentanyl, methyl-substituted fentanyls and other analogues

3-Methylfentanyl showed the strongest analgesic activity among these compounds, and the most frequently abused fentanyl derivative, α-methylf fentanyl, also showed quite strong activity.

Mass spectral and GC data of drugs, poisons, pesticides, pollutants and their metabolites: Part 3 mass spectra (m/z222 to 777 amu).

Volume 1 (Methods, Tables). Methods. 1 Introduction. 2 Experimental Section. 2.1 Origin and choice of samples. 2.2 Sample preparation. 2.2.1 Standard extraction procedures. 2.2.1.1 Standard…

Possible involvement of multiple cytochrome P450S in fentanyl and sufentanil metabolism as opposed to alfentanil.