Biotransformation of Sumatriptan by <i>Staphylococcus aureus</i>, <i>Bacillus subtilis</i>, <i>Pseudomonas aeruginosa</i> and <i>Salmonella enterica</i> subsp. <i>enterica</i>

Abstract

This study aimed at the biotransformation of sumatriptan by Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa and Salmonella enterica subsp. enterica and the identification of the drug metabolites by liquid chromatography–mass spectrometry. The drug was incubated with the organisms in tryptic soya broth at 37 °C. The broth was filtered and subjected to liquid chromatography–mass spectrometry. The metabolites identified by the use of mass spectral (+ve ion mode) fragmentation patterns were (3-methylphenyl)methanethiol (Bacillus subtilis), 1-(4-amino-3-ethylphenyl)-N-methylmethanesulfonamide (Salmonella enterica subsp. enterica) and 1-{4-amino-3-[(1E)-3-(dimethylamino)prop-1-en-1-yl]phenyl}methanesulfinamide (Salmonella enterica subsp. enterica, Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus). These metabolites exhibit high gastrointestinal absorption, no blood–brain barrier permeability (except (3-methylphenyl)methanethiol), a bioavailability score of 0.55 and no inhibitory effect on CYP2C19, CYP2C9, CYP2D6, CYP3A4 or cytochrome P450 1A2 (except (3-methylphenyl)methanethiol), as determined by SwissADME software ver. 2024. The metabolites appear to be more toxic than the parent drug, as suggested by their calculated median lethal dose values. All four organisms under investigation transformed sumatriptan to different chemical substances that were more toxic than the parent drug.

Keywords

• bacterial transformation
• triptan
• LC-MS
• metabolism
• biodegradation