Metabolism and the urinary excretion profile of the recently scheduled designer drug N-Benzylpiperazine (BZP) in the rat.
The metabolism of N-benzylpiperazine (BZP), a recently scheduled designer drug, in the rat has been studied by analyzing its urinary metabolites. p-Hydroxy-BZP (p-OH-BZP) was unequivocally identified as the main metabolite along with a minor metabolite m-hydroxy-BZP (m-OH-BZP), using gas chromatography-mass spectrometry and high-performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI MS). The time-course excretion profiles of BZP, p-OH-BZP, and m-OH-BZP in the rats were investigated after a single intraperitoneal dosing of 5 mg/kg BZP, by using an optimized analytical procedure that combines solid-phase extraction and LC-ESI MS determination. The cumulative amounts excreted within the first 48 h were approximately 25% for p-OH-BZP and 2% for m-OH-BZP, whereas 6.7% dose of the parent drug BZP was excreted unchanged within 36 h post-dosing. The concentration ratio of p-OH-BZP to m-OH-BZP was 11.6 in the first 4 h, but it increased to 22.7 in 48 h with the elapsed time post-dosing. Most of p-OH-BZP was excreted in urine within approximately 36 h post-dosing, with approximately 50% appearing as the glucuronide conjugate. The present results suggest that p-OH-BZP is the most relevant metabolite to be detected for the proof of BZP intake in the forensic and clinical analysis of human urine.
Tsutsumi
Hiroe
H
Forensic Science Laboratory, Osaka Prefectural Police Headquarters, 1-3-18 Hommachi, Chuo-ku, Osaka 541-0053, Japan. htutuoppe@yahoo.co.jp
Katagi
Munehiro
M
Miki
Akihiro
A
Shima
Noriaki
N
Kamata
Tohru
T
Nakajima
Kunio
K
Inoue
Hiroyuki
H
Kishi
Tohru
T
Tsuchihashi
Hitoshi
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D015198:Designer Drugs; D005554:Forensic Medicine / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D008297:Male; D010879:Piperazines / Q000493:pharmacokinetics* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D015813:Substance Abuse Detection / Q000379:methods*
D015198:Designer Drugs; C461488:N-benzylpiperazine; D010879:Piperazines