Pyrrolidinyl Synthetic Cathinones alpha-PHP and 4F-alpha-PVP Metabolite Profiling Using Human Hepatocyte Incubations | |
Carlier, Jeremy2,3,4; Diao, Xingxing1,2; Giorgetti, Raffaele3; Busardo, Francesco P.3; Huestis, Marilyn A.2,5 | |
刊名 | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES |
2021 | |
卷号 | 22期号:1页码:17 |
关键词 | alpha-PHP PV7 4F-alpha-PVP novel psychoactive substance synthetic cathinone bath salt hepatocyte metabolism liquid chromatography-high resolution tandem mass spectrometry |
DOI | 10.3390/ijms22010230 |
通讯作者 | Busardo, Francesco P.(fra.busardo@libero.it) |
英文摘要 | 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, alpha-pyrrolidinohexaphenone (alpha-PHP) and 4 ''-fluoro-alpha-pyrrolidinovalerophenone (4F-alpha-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 alpha-PHP dihydroxy-pyrrolidinyl, alpha-PHP hexanol, alpha-PHP 2 '-keto-pyrrolidinyl-hexanol, and alpha-PHP 2 '-keto-pyrrolidinyl as markers of alpha-PHP use, and 4F-alpha-PVP dihydroxy-pyrrolidinyl, 4F-alpha-PVP hexanol, 4F-alpha-PVP 2 '-keto-pyrrolidinyl-hexanol, and 4F-alpha-PVP 2 '-keto-pyrrolidinyl as markers of 4F-alpha-PVP use. These results represent the first data available on 4F-alpha-PVP metabolism. The metabolic fate of alpha-PHP was previously studied using human liver microsomes and urine samples from alpha-PHP users. We identified an additional major metabolite (alpha-PHP dihydroxy-pyrrolidinyl) that might be crucial for documenting exposure to alpha-PHP. Further experiments with suitable analytical standards, which are yet to be synthesized, and authentic specimens should be conducted to confirm these results. |
资助项目 | Intramural Research Program of the National Institute on drug abuse, National Institutes of Health ; Presidency of the Ministers Council, Department of Antidrug Policy[CUP: F75J18000390005] |
WOS关键词 | THERMAL-DEGRADATION ; DESIGNER DRUGS ; RAT URINE ; PHASE-I ; GC-MS ; IDENTIFICATION ; CANNABINOIDS ; PYRROLIDINOVALEROPHENONE ; QUANTIFICATION ; DERIVATIVES |
WOS研究方向 | Biochemistry & Molecular Biology ; Chemistry |
语种 | 英语 |
出版者 | MDPI |
WOS记录号 | WOS:000606055700001 |
内容类型 | 期刊论文 |
源URL | [http://119.78.100.183/handle/2S10ELR8/296119] |
专题 | 中国科学院上海药物研究所 |
通讯作者 | Busardo, Francesco P. |
作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.NIH, Chem & Drug Metab Sect, Intramural Res Program, NIDA, Baltimore, MD 21224 USA 3.Marche Polytech Univ, Sect Legal Med, Dept Excellence Biomed Sci & Publ Hlth, Unit Forens Toxicol, I-60126 Ancona, Italy 4.Sapienza Univ Rome, Sect Legal Med Forens & Orthoped Sci, Dept Anat, Histol,Unit Forens Toxicol, I-00198 Rome, Italy 5.Thomas Jefferson Univ, Inst Emerging Hlth Profess, Philadelphia, PA 19107 USA |
推荐引用方式 GB/T 7714 | Carlier, Jeremy,Diao, Xingxing,Giorgetti, Raffaele,et al. Pyrrolidinyl Synthetic Cathinones alpha-PHP and 4F-alpha-PVP Metabolite Profiling Using Human Hepatocyte Incubations[J]. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,2021,22(1):17. |
APA | Carlier, Jeremy,Diao, Xingxing,Giorgetti, Raffaele,Busardo, Francesco P.,&Huestis, Marilyn A..(2021).Pyrrolidinyl Synthetic Cathinones alpha-PHP and 4F-alpha-PVP Metabolite Profiling Using Human Hepatocyte Incubations.INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES,22(1),17. |
MLA | Carlier, Jeremy,et al."Pyrrolidinyl Synthetic Cathinones alpha-PHP and 4F-alpha-PVP Metabolite Profiling Using Human Hepatocyte Incubations".INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES 22.1(2021):17. |
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