Abstract
The stability and degradation pathways of a new semi-synthetic cephalosporin, 1-[[(6R, 7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6, 7-dihydro-5H-1-pyrindinium hydroxide, inner salt, 72-(Z)-(O-methyloxime) sulfate (cefpirome sulfate, HR 810), were studied.Cefpirome in various buffer solutions was allowed to stand at 40°C and its degradation patterns were investigated by high performance liquid chromatography. Cefpirome was stable in the region of pH 4-7 and slightly unstable beyond this range.In aqueous solution from the neutral to alkaline regions, the produced degradation products were : 1-[[(6R, 7S)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6, 7-dihydro-5H-1-pyrindinium hydroxide, inner salt, 72-(Z)-(O-methyloxime)(epi-cefpirome); 1-[[(6R, 7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-3-en-3-hy]methyl]-6, 7-dihydro-5H-1-pyrindinium hydroxide, inner salt, 72-(Z)-(O-methyloxime)(Δ2-cefpirome); 2-[[(2-amino-4-thiazolyl)((Z)-methoxyimino)acetyl]amino]acetaldehyde; and 6, 7-dihydro-5H-1-pyrindine. On the other hand, 1-[[(6R, 7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6, 7-dihydro-5H-1-pyrindinium hydroxide, inner salt, 72-(E)-(O-methyloxime) (anti-cefpirome), 2-[[(2-amino-4-thiazolyl)-((Z)-methoxyimino)-acetyl]aminomethyl]-1, 2, 5, 7-tetrahydro-7-oxo-4H-furo[3, 4-d]-[1, 3]thiazine, and 6, 7-dihydro-5H-1-pyrindine were produced in strongly acidic solution or under irradiation by artificial sunlight.
