Electrochemical oxidation of 5-hydroxymethyl tolterodine and identification of its oxidation products using liquid chromatography and mass spectrometry

•Two electrochemically oxidable centers were disclosed in 5-HMT molecule.•Diisopropylamine moiety underwent electro-oxidative cleavage at higher pH.•Hydroxybenzyl alcohol moiety was electro-oxidized to respective aldehyde.•Formic acid arose from electro-oxidation of hydroxybenzyl alcohol.

The electrochemical behavior of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of antimuscarinic drugs tolterodine and fesoterodine used to treat urge incontinence and overactive bladder, was investigated using cyclic and differential pulse voltammetry at glassy carbon electrode. Electrooxidation of 5-HMT proceeds as a complex pH-dependent process. Controlled potential electrolysis of 5-HMT solutions was performed at platinum gauze electrode in aqueous-methanolic media. Electrolyzed solutions were analyzed using ultra performance liquid chromatography with electrospray ionization quadrupole time-of-flight mass spectrometry. Two main oxidation centers of the studied molecule were located: the p-hydroxybenzyl alcohol group and the tertiary amino group. Oxidation of the first center proceeds in several steps leading to the formation of 5-formyl tolterodine, p-benzoquinone derivative and several dimeric, hydroxylated and methoxylated products depending on pH of the solution and electrode potential. The second center is oxidized preferentially in alkaline media at higher potentials under the hydrolytic cleavage of diisopropylamine and formation of corresponding aldehydes. Mechanism of the electrochemical oxidation of 5-HMT has been proposed.

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