Acid catalysed degradation of some spiramycin derivatives found in the antibiotic bitespiramycin.
Bitespiramycin is a novel antibiotic containing a number of 4''-acylated spiramycin derivatives (isovalerylspiramycins I-III, butanoylspiramycin III, propanoylspiramycin III and acetylspiramycin III) as major components. These spiramycin derivatives are susceptible to degradation in acid solution. Liquid chromatography-ion trap mass spectrometry (LC/MS(n)) was used to study the degradation of these spiramycin derivatives in simulated gastric fluid at 37 degrees C. All derivatives degraded by first-order reactions for which rate constants (k) and half-lives (t(1/2)) were calculated. Acyl groups at position 3 had less effect on acid-stability of spiramycin derivatives than acyl groups at position 4''. The introduction of 4''-acyl groups enhanced the acid-stability of spiramycin derivatives and altered the degradation pathway in simulated gastric fluid such that loss of forosamine rather than loss of mycarose becomes the major degradation pathway.
Shi
Xiangguo
X
Laboratory of Drug Metabolism and Pharmacokinetics, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.
Zhang
Shuqiu
S
Fawcett
J Paul
JP
Zhong
Dafang
D
D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D002384:Catalysis; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D015572:Spiramycin / Q000031:analogs & derivatives* / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D015572:Spiramycin; C423662:carrimycin