PozLab Sp z o.o., Parcowa, Poznań, Poland.
Drug Dev Ind Pharm. 2012 Aug;38(8):1024-8. doi: 10.3109/03639045.2011.637053. Epub 2011 Nov 29.
The stability of N-[(morpholine)methylene]-daunorubicin hydrochloride (MMD) was investigated in the pH range 0.44-13.54, at 313, 308, 303 and 298 K. The degradation of MMD as a result of hydrolysis is a pseudo-first-order reaction described by the following equation: ln c = ln c(0) - k(obs)• t. In the solutions of hydrochloric acid, sodium hydroxide, borate, acetate and phosphate buffers, k(obs) = k(pH) because general acid-base catalysis was not observed. Specific acid-base catalysis of MMD comprises the following reactions: hydrolysis of the protonated molecules of MMD catalyzed by hydrogen ions (k(1)) and spontaneous hydrolysis of MMD molecules other than the protonated ones (k(2)) under the influence of water. The total rate of the reaction is equal to the sum of partial reactions: k(pH) = k(1) • a(H)+ • f(1) + k(2) • f(2) where: k(1) is the second-order rate constant (mol(-1) l s(-1)) of the specific hydrogen ion-catalyzed degradation of the protonated molecules of MMD; k(2) is the pseudo-first-order rate constant (s(-1)) of the water-catalyzed degradation of MMD molecules other than the protonated ones, f(1) - f(2) are fractions of the compound. MMD is the most stable at approx. pH 2.5.
N-[(吗啉)亚甲基]-盐酸柔红霉素（MMD）在 pH 值为 0.44-13.54 的范围内，在 313、308、303 和 298 K 下的稳定性进行了研究。MMD 由于水解而降解是一个伪一级反应，由以下方程描述：ln c = ln c(0) - k(obs)• t。在盐酸、氢氧化钠、硼酸盐、乙酸盐和磷酸盐缓冲液的溶液中，k(obs) = k(pH)，因为没有观察到一般酸碱催化。MMD 的特殊酸碱催化包括以下反应：质子化的 MMD 分子的水解由氢离子（k(1)）催化和质子化的 MMD 分子以外的 MMD 分子的自发水解（k(2)）在水的影响下进行。反应的总速率等于各部分反应的总和：k(pH) = k(1) • a(H)+ • f(1) + k(2) • f(2)，其中：k(1)是质子化的 MMD 分子的特殊氢离子催化降解的二级速率常数（mol(-1) l s(-1)）；k(2)是质子化的 MMD 分子以外的 MMD 分子的水催化降解的伪一级速率常数（s(-1)），f(1) - f(2)是化合物的分数。MMD 在约 pH 2.5 时最稳定。
