氟胞嘧啶注射液稳定性预测

氟胞嘧啶为5-氟-4-氨基-2(1 H)-嘧啶酮(简称5-FC),系近年来发展起来的新型抗真菌药。Florey曾介绍薄层—紫外分光光度法测定氟胞嘧啶的含量,研究其制剂的稳定性,但其原文未见公开发表。本文报告应用反相离子对色谱法测定注射液中氟胞嘧啶的含量,并按照化学动力学方法预测氟胞嘧啶注射液的稳定性。

PREDICTION OF STABILITY OF FLUCYTOSINE INJECTIONS

Kinetics of hydrolysis of flueytosine (5-FC) was discussed to predict the stability of flucytosine injections. Reverse phase ion-pair HPLC was used to determine 5-FC in flucytosine injections. The stability of the injections was examined with the classical isothermal method. The use of HPLC made it possible to determine the different contents of 5-FC in the presence of its degradation products. According to Arrhenius rule, the activation energy of 5-FC was 27.8 kcal. mol^-1. Since its main degradation product——fluorouracil is the factor in flucytosine clinical toxicity, shelf life was calculated in t_0.999 and t_0.998. At 25℃ it was about half a year (t_0.999) and 1.5 years (t_(0.998)). At 15～20℃ it was about 1.5 years (t_0.999) and about 3 years (t_(0.998)).