Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations.

Authors

Jeremy Carlier, National Institutes of Health, Baltimore, MD, Marche Polytechnic University
Xingxing Diao, National Institutes of Health, Baltimore, MD, Chinese Academy of Sciences
Raffaele Giorgetti, Marche Polytechnic University
Francesco P Busardò, Marche Polytechnic University
Marilyn A. Huestis, Thomas Jefferson University, National Institutes of Health, Baltimore, MDFollow

Document Type

Article

Publication Date

12-28-2020

Comments

This is the final published version of the article from the International Journal of Molecular Science, 2020 Dec 28;22(1):230.

The article is also available at the journal's website: http://doi.org/10.3390/ijms22010230.

Copyright. The Authors.

Abstract

For more than ten years, new synthetic cathinones (SCs) mimicking the effects of controlled cocaine-like stimulants have flooded the illegal drug market, causing numerous intoxications and fatalities. There are often no data on the pharmacokinetics of these substances when they first emerge onto the market. However, the detection of SC metabolites is often critical in order to prove consumption in clinical and forensic settings. In this research, the metabolite profile of two pyrrolidinyl SCs, α-pyrrolidinohexaphenone (α-PHP) and 4''-fluoro-α-pyrrolidinovalerophenone (4F-α-PVP), were characterized to identify optimal intake markers. Experiments were conducted using pooled human hepatocyte incubations followed by liquid chromatography-high-resolution tandem mass spectrometry and data-mining software. We suggest α-PHP dihydroxy-pyrrolidinyl, α-PHP hexanol, α-PHP 2'-keto-pyrrolidinyl-hexanol, and α-PHP 2'-keto-pyrrolidinyl as markers of α-PHP use, and 4F-α-PVP dihydroxy-pyrrolidinyl, 4F-α-PVP hexanol, 4F-α-PVP 2'-keto-pyrrolidinyl-hexanol, and 4F-α-PVP 2'-keto-pyrrolidinyl as markers of 4F-α-PVP use. These results represent the first data available on 4F-α-PVP metabolism. The metabolic fate of α-PHP was previously studied using human liver microsomes and urine samples from α-PHP users. We identified an additional major metabolite (α-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to α-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results.

Recommended Citation

Carlier, Jeremy; Diao, Xingxing; Giorgetti, Raffaele; Busardò, Francesco P; and Huestis, Marilyn A., "Pyrrolidinyl Synthetic Cathinones α-PHP and 4F-α-PVP Metabolite Profiling Using Human Hepatocyte Incubations." (2020). Institute of Emerging Health Professions Faculty Papers. Paper 7.
https://jdc.jefferson.edu/iehpfp/7

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English