Methylsuccinate and mesaconate in urine of patients treated with sodium benzoate

Two unusual peaks were found on gas chromatography of urine from four hyperammonemic patients treated with sodium benzoate. These peaks were identified by gas chromatography/mass spectrometric analyses as methylsuccinate and mesaconate. Of the two unusual substances, methylsuccinate was found to be a contaminant of sodium benzoate administered for the treatment of hyperammonemia. However, mesaconate was not a contaminant of sodium benzoate, though it could be detected in all urine samples from hyperammonemic patients treated with sodium benzoate. Mesaconate can be produced from methylsuccinate in vivo. Considering that mesaconate is an inhibitor of fumarase, the toxic effects of sodium benzoate may be attributable to the mesaconate. It is recommended that methylsuccinate-free sodium benzoate should be used for the treatment of hyperammonemia.