S-(N-メチルカルバモイル)-L-システインエチルエステル塩酸塩の水溶液中での安定性(<特集>医薬品の分析)

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Stability of new antitumor agent, S-(N-methylcarbamoyl)-L-cysteine ethyl ester hydrochloride (Y-6430) was studied. Y-6430 and its analogues were incubated in 20 mM phosphate buffer (pH 7.5) at 37℃ and residual contents were determined by high performance liquid chromatography (HPLC) with a photodiode array detector {column : Cosmosil 5C_<18> ; mobile phase : linear gradient from 20 mM KH_2PO_4 to 20 mM KH_2PO_4-Methanol (1 : 1) in 20 min ; flow rate : 1.0 ml/min}. Half-lives of Y-6430 and its analogues in the buffer were 200 min and 50〜10 min, respectively. Decomposition of Y-6430 was remarkably accelerated by the addition of L-cysteine or L-glutamine. Decomposition products from Y-6430 solution incubated with or without L-cysteine were isolated by HPLC and their chemical structures were proposed on the basis of their ultraviolet absorption, nuclear magnetic resonance and mass spectra. The products isolated from Y-6430 solution incubated with L-cysteine were formed as the result of elimination of its ethyl moiety. On the other hand, elimination of N-methylamine, N-methylcarbamoyl and N-methylisothiocyanate moieties predominated in the solution incubated without L-cysteine.
社団法人日本分析化学会の論文
1986-03-05