Stability and degradation pattern of cefpirome (HR 810) in aqueous solution.
The stability and degradation pathways of a new semi-synthetic cephalosporin, 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-ox o-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-6,7-dihydro-5H-1- pyridinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) sulfate (cefpirome sulfate, HR 810), were studied. Cefpirome in various buffer solutions was allowed to stand at 40 degrees 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-5 H-1- pyridinium hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) (epi-cefpirome); 1-[[(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-2-carboxy-8-ox o-5-thia-1-azabicyclo[4.2.0]oct-3-en-3-yl]methyl]-6,7-dihydro-5H-1- pyridinum hydroxide, inner salt, 7(2)-(Z)-(O-methyloxime) (delta 2-cefpirome); 2-[[(2-amino-4-thiazolyl)((Z)-methoxy-imino)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-pyridinium++ + hydroxide, inner salt, 7(2)-(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.
Sugioka
T
T
Pharma Research Laboratories, Hoechst Japan Limited, Saitama.
Asano
T
T
Chikaraishi
Y
Y
Suzuki
E
E
Sano
A
A
Kuriki
T
T
Shirotsuka
M
M
Saito
K
K
D002511:Cephalosporins / Q000032:analysis*; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D012996:Solutions; D000097572:Cefpirome
D002511:Cephalosporins; D012996:Solutions; D000097572:Cefpirome