Vancomycin degradation

Backes, D.W., Aboleneen, H.I., and Simpson, J.I., Quantitation of vancomycin and its crystalline degradation product (CDP-1) in human serum by high performance liquid chromatography, 7. Pharm. Biomed. Anal., 16, 1281, 1998. 

Ghassempour, A. et al., Crystalline degradation products of vancomycin as a new chiral stationary phase for liquid chromatography, Chromatographia, 61, 151, 2005. 

Intermediate for the synthesis of actinoidic acid, degradation product of vancomycin... 

Dalbaheptides are levorotatory. The absolute configuration of vancomycin was determined by x-ray analysis of degradation product CDP-1. 

Fluorescence polarization immunoassay determination of serum vancomycin concentrations can result in falsely high vancomycin concentrations in excess of 30-80% in patients with renal dysfunction. This is due to the formation of a non-toxic, non-microbiologically active pseudometabolite, the vancomycin crystalline degradation product (132). A report on a 48-year-old man underlies the significance of resulting underdosing and eventually suboptimal clinical response (133). 

The first structural work on vancomycin were degradation studies carried out by Marshall [208] followed by extensive NMR examinations in the laboratory of Williams [209]. On the basis of these pioneering studies and on the X-ray analysis of the degradation product CDP-1 [210], Harris and Harris published the complete structure of vancomycin in 1982 [211]. The determination of the vancomycin structure then served as the basis for the structural characterization of hundreds of natural and semisynthetic glycopeptide antibiotics. 

Vancomycin hydrochloride is always administered intravenously (never intramuscularly), either by slow injection or hy continuous infusion, for the treatment of systemic infections. In shott-term therapy, the toxic side reactions arc usually slight, hut continued u.sc may lead to impaired auditory acuity, renal damage, phlebitis, and rashes. Bccau.se it is nut assorted or signilicantly degraded in the gastrointc.stinal tract, vancomycin may he administered orally fur the treatment of staphylococcal enterocolitis and for pseudomembranous colitis associated with clindamycin therapy. Some conversion to aglucovancomycin likely (Kcurs in the low pH of the stomach. The latter retains about three-fourths of the activity of vancomycin. 

Organisms in which resistance has increased most dramatically include enterococci, pneumococci, and Mycobacterium tuberculosis. Enterococci have been isolated with multiple resistance patterns. They may be resistant to /S-lactams (by virtue of -lactamase production, altered penicillin-binding proteins [PBPs], or both), vancomycin (via alterations in peptidoglycan synthesis), and high levels of aminoglycosides (via enzymatic degradation). 

The degradation kinetics of vancomycin hydrochloride were investigated in 2 mM aqueous solutions at 50 °C at pH 1-9.8, and amine pJCa values were titrated by H-NMR at 50 °C. The deamidation of vancomycin between pH 3 and 9.8 followed pseudo-first order kinetics. In addition, the pJCa values were lower than those reported at 25 °C. Rate constants obtained from curve fitting die pH-rate profile to the observed data indicate that the reactivity of vancomycin toward deamidation in die region of pH 6-9 is influenced by its ionic state.. .. the ionic state of vancomycin may influence its degradation rate."... 

Degradation of the avoparcin complex, a glycopeptide antibiotic mixture related to vancomycin and ristocetin, has yielded a variety... 

Revankar, H. M. Kulkarni, M. V. Joshi, S. D. More, U. A. Synthesis, biological evaluation and docking studies of 4-aryloxymethyl coumarins derived from substructures and degradation products of vancomycin. Eur. J. Med. Chem. 2013, 70,750-757. 

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