New designer drug alpha-pyrrolidinovalerophenone (PVP): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques.
The aim of the present study was to identify the metabolites of the new designer drug alpha-pyrrolidinovalerophenone (PVP) in rat urine using GC/MS techniques. Eleven metabolites of PVP could be identified suggesting the following metabolic steps: hydroxylation of the side chain followed by dehydrogenation to the corresponding ketone; hydroxylation of the 2''-position of the pyrrolidine ring followed by dehydrogenation to the corresponding lactam or followed by ring opening to the respective aliphatic aldehyde and further oxidation to the respective carboxylic acid; degradation of the pyrrolidine ring to the corresponding primary amine; and hydroxylation of the phenyl ring, most probably in the 4'-position. The authors' screening procedure for pyrrolidinophenones allowed the detection of PVP metabolites after application of a dose corresponding to a presumed user's dose. In addition, the involvement of nine different human cytochrome P450 (CYP) isoenzymes in the side chain hydroxylation of PVP was investigated and CYP 2B6, 2C19, 2D6, and 3A4 were found to catalyze this reaction.
Sauer
Christoph
C
Department of Experimental and Clinical Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, Saarland University, D-66421 Homburg (Saar), Germany.
Peters
Frank T
FT
Haas
Claudia
C
Meyer
Markus R
MR
Fritschi
Giselher
G
Maurer
Hans H
HH
D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015198:Designer Drugs / Q000032:analysis* / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D006900:Hydroxylation; D008297:Male; D011759:Pyrrolidines / Q000378:metabolism* / Q000652:urine*; D051381:Rats; D017208:Rats, Wistar; D015813:Substance Abuse Detection / Q000379:methods
D015198:Designer Drugs; D011759:Pyrrolidines; C542924:alpha-pyrrolidinovalerophenone; D003577:Cytochrome P-450 Enzyme System