Nuclear magnetic resonance analysis of methotrimeprazine (levomepromazine) hydroxylation in humans.

Two monohydroxylated metabolites of methotrimeprazine (levomepromazine), which previously have been identified in plasma and urine from psychiatric patients, were synthesized by nonenzymatic, FeCl2-catalyzed oxidation, isolated, and purified by preparative reversed-phase HPLC. Mass spectrometric analysis gave identical spectra for the two compounds, but did not reveal the positions of the OH groups. However, 1H NMR spectroscopy at 200 MHz demonstrated that one of the compounds, which had the shortest GC retention time on an OV-17 column, was hydroxylated in the 3-position on the phenothiazine nucleus, and that the other derivative was hydroxylated in the 7-position. The metabolism of methotrimeprazine differs, therefore, from that of its congener chlorpromazine, which is hydroxylated mainly in the 7-position in humans.