Early and Mid-Term Disposition of α-PVP and its unknown Metabolites in Urine and Oral Fluid Through a Multi-Analytical Hyphenated Approach Following a Single Non-Controlled Administration to Healthy Volunteers

• Published in: The AAPS journal Vol. 27; no. 1; p. 25
• Main Authors: Di Trana, Annagiulia, La Maida, Nunzia, de la Rosa, Georgina, Di Giorgi, Alessandro, Graziano, Silvia, Aldhaehri, Khaled, Papaseit, Esther, Hladun, Olga, Farré, Magí, Pérez, Clara, Pichini, Simona
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 09.01.2025
• Subjects: Adult; Biochemistry; Biomedical and Life Sciences; Biomedicine; Biotechnology; Chromatography, Liquid - methods; Female; Gas Chromatography-Mass Spectrometry - methods; Healthy Volunteers; Humans; Male; Pharmacology/Toxicology; Pharmacy; Psychotropic Drugs - administration & dosage; Psychotropic Drugs - metabolism; Psychotropic Drugs - pharmacokinetics; Psychotropic Drugs - urine; Pyrrolidines - administration & dosage; Pyrrolidines - metabolism; Pyrrolidines - pharmacokinetics; Pyrrolidines - urine; Research Article; Saliva - chemistry; Saliva - metabolism; Tandem Mass Spectrometry - methods; Young Adult; GC–MS/MS; pharmacokinetics; metabolism; α-PVP; LC-ESI-HRMS/MS; synthetic cathinones
• ISSN: 1550-7416; 1550-7416
• DOI: 10.1208/s12248-024-01012-7

Nowadays, synthetic cathinones (SCs) is the second more representative subclass of New Psychoactive Substances, accounting for 104 analogues in the illegal market. Since its first report in 2011, α-pyrrolidinovalerophenone (α-PVP) gained popularity among drug users, provoking an increased number of intoxications. Nonetheless, pharmacokinetics data is still limited in the literature. An observational non-controlled naturalistic study on 8 healthy volunteers was conducted to assess the α-PVP and β-OH-α-PVP concentrations in OF and urine, after snorting 10 mg or 20 mg of α-PVP. A multi-analytical approach based on GC-EI-MS/MS and LC-HESI-HRMS/MS was developed and fully validated for the analytes quantification, while four untargeted LC-HESI-HRMS/MS methods in full-MS and ddMS 2 were set up for unknown metabolites characterization in urine samples assisted by a dedicated data mining software. In OF, α-PVP reached a mean C max of 762 ± 323 ng/mL at 1 h after 10 mg administration, while a C max of 2,900 ± 1,373 ng/mL at 47 min after 20 mg dose. In urine, a total α-PVP mean amount of 179.2 ± 94.9 µg was accumulated after 10 mg dose, (27.2 ± 9.8 µg between 0-2 h and 152.0 ± 98.2 µg between 2-5 h), while a total amount of 122.9 ± 44.0 µg, of (36.2 ± 16.5 and 86.7 ± 28.3 µg between 0–2 and 2-5 h, respectively) was detected after 20 mg dose. Among the 10 identified metabolites, β-OH-α-PVP was a minor metabolite (total amount: 56.4 ± 27.1 and 69.1 ± 38.1 µg after 10 mg and 20 mg). The N-butanoic acid metabolite was the most abundant, detected also as glucuronide. In conclusion, α-PVP showed a later time peak than non-pyrrolidine SCs, with comparable C max. The pyrrolidine ring oxidative opening produced the most abundant urinary metabolite, independently from the dose.