Influence of Blood Proteins on Biomedical Analysis. IX. : Protective Effects of Human Serum Proteins on Anion-Induced Degradation of Gliclazide

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Gliclazide, 1-(3-azabicyclo[3.3.0]oct-3-yl)-3-(p-tolylsulfonyl)urea, an oral hypoglycemic drug having the sulfonylurea structure, was completely degraded in a medium containing more than 0.2M chloride or bromide ion at 37℃ after 24h. Other sulfonylureas, tolazamide and glycopyramide, were also degraded in the presence of chloride ion, but tolbutamide, acetohexamide, chlorpropamide and glibenclamide were not. Fluoride, carbonate, acetate, sulfate and phosphate ions and both sodium and potassium cations induced slight degradation of gliclazide. Two degradation products were isolated, crystallized, and identified as a hydrazine compound (3-azabicyclo[3.3.0]oct-3-yl-amine monohydrochloride) and p-toluenesulfonamide based on mp, ultraviolet, infrated, proton nuclear magnetic resonance, mass spectra and high performance liquid chromatography data. The anion-induced gliclazide degradation was dose-dependently depressed by human serum albumin or other proteins. It was completely depressed by albumin at over 0.3 mg/ml. Other serum proteins, α, β and γ-globulins, depressed the anion (Cl^-)-induced gliclazide degradation similarly to albumin.
社団法人日本薬学会の論文
1986-07-25