In vivo and in vitro metabolism studies of glaucine, a new herbal high by GC-MS, LC-MS, LC-HR-MS, and NMR techniques

The isoquinoline alkaloid Glaucine was described as an ingredient of legal highs and gained the interest of clinical and forensic toxicologist. So far, only few data on its pharmacokinetic properties was investigated. The aims of the present studies were to elucidate the metabolic fate of glaucine in vivo (rat) by GC-MS and LC-HR-MS techniques, to confirm the human main phase I metabolites in vitro, to identify the involved CYP isoenzyme using heterologically expressed single CYPs, to determine the Michaelis-Menten constants Km, and Vmax in human liver microsomes, and finally, to investigate the detectability by the authors standard urine screening approaches. In rats, glaucine was mainly Oand N-dealkylated followed by conjugation to glucuronides or sulfates. The following CYP isoforms were mainly involved in these reactions: CYP1A2, CYP2C19, CYP2D6, CYP3A4, and CYP3A5. The kinetic profiles of all metabolite formations followed classic Michaelis-Menten behavior and the Km values were between 25-140 μM and the Vmax values between 0.10 1.92 pmol/min/pmol. Toxicological detection should be focused on the demethyl metabolites and the corresponding glucuronides and/or sulfates.