Studies on β-Lactam Antibiotics for Medicinal Purpose. XIV. Stability and Degradation Pattern of Sodium 7β-[(2R, 3S)-2-(4-Ethyl-2, 3-dioxo-1-piperazinecarboxamido)-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1982) in Aqueous Solution

Abstract

The stability and degradation of sodium 7β-[(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate (T-1982) in aqueous solution were investigated. The solutions of T-1982 of various pH (μ=0.5) were kept at 35°C, and its degradation was followed by HPLC. T-1982 was stable in the range of pH 3.0-6.0, slightly unstable at lower pH and markedly unstable at higher pH than this range. It was confirmed that in alkaline solution, 7β-[(2R, 3S)-2-[3-[2-(N-ethyl-N-oxaloamino) ethyl] ureido]-3-hydroxybutanamido]-7α-methoxy-3-[(1-methyl-1H-tetrazol-5-yl)-thiomethyl]-3-cephem-4-carboxylic acid (T-1982A), 7α-methoxy-7β-[(5-methyl-2-oxooxazolidin-4-yl) carboxamido-] 3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylic acid (T-1982B) and 1-ethyl-2, 3-dioxopiperazine (T-1982C) were produced, and that in acidic solution, 5-mercapto-1-methyl-1H-tetrazole (T-1982F), (2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-N-(1-formyl-1-methoxy) methyl-3-hydroxybutanamide (T-1982H) and methyl [(2R, 3S)-2-(4-ethyl-2, 3-dioxo-1-piperazinecarboxamido)-3-hydroxybutanamido] acetate (T-1982J) were produced.