On the metabolism of the amphetamine-derived antispasmodic drug mebeverine: Gas chromatography-mass spectrometry studies on rat liver microsomes and on human urine

We describe gas chromatography-mass spectrometry studies of the metabolism of the antispasmodic drug mebeverine [Duspatal, (MB)]. MB is the veratric a cid (VA) ester of 4-{ethyl-[2-(4-methoxyphenyl)-1-methylethyl]amino}butan-1 -ol (MB-OH), which is an N-substituted ethylamphetamine derivative. The met abolites were first identified in rat liver microsome incubates and then de tected in urine samples of volunteers through the use of electron impact an d positive chemical ionization gas chromatography-mass spectrometry. Urinar y conjugates were enzymatically cleaved before analysis. The following phas e I metabolites of MB could be identified: VA, O-demethyl VA (vanillic and/ or isovanillic acid), O-bisdemethyl VA (protocatechuic acid), MB-OH, hydrox y MB-OH, O-demethyl MB-OH, O-demethyl-hydroxy MB-OH, N-desethyl MB-OH, N-de sethyl-O-demethyl MB-OH, N-de(hydroxybutyl) MB-OH (methoxy-ethylamphetamine ), N- de(hydroxybutyl)-O-demethyl MB-OH (hydroxy-ethylamphetamine), and N-b isdealkyl MB-OH (p-methoxyamphetamine, known as the designer drug PMA). The following, partly overlapping metabolic pathways of MB could be postulated : ester hydrolysis, O-demethylation, ring hydroxylation, N- deethylation, a nd N-de(hydroxybutylation). The latter pathway led to ethylamphetamine deri vatives and bisdealkylation led to PMA, which are substances of forensic in terest. The metabolites containing alcoholic or phenolic hydroxy groups wer e partly excreted into urine as conjugates.