Journal of Pharmaceutical Sciences p. 896 - 902 (1984)
Update date:2022-08-05
Topics:
Kirsch
Notari
The kinetics of conversion of the prodrug ancitabine to the anti-cancer drug cytarabine have been studied in aqueous solutions in the pH range of 1.5-10.7, temperature range of 19.5-80.0°C, ionic strength range of 10-4 to 1.5, and in the presence of several general-base catalysts. Under all conditions ancitabine was quantitatively converted to cytarabine. The pH-rate profiles were linear with slope = 1 in alkaline pH, becoming pH independent in the region of maximum stability at pH ≤4, where buffer catalysis was found to be insignificant and k(obs) ? (1.12 x 1011 h-1)·exp {-10121 deg/T}. At 30°C, pH ≤4, it is calculated that an aqueous ancitabine solution will maintain 90% of its initial concentration for 12 d. A novel method for measuring general-base catalysis in competition with predominating a specific-base catalysis and in the presence of secondary salt effects a constant ionic strength was developed. Three mechanisms of hydrolytic prodrug conversion are proposed: nucleophilic hydroxide addition, general base-assisted nucleophilic water attack, and spontaneous water attack.
View MoreHangzhou yi lu biont technology Co., LTD
Contact:+86-571-88152630
Address:Hangzhoushi HuafengRoad Yicheng3Building1001room.
TIANJIN FESTO CHEMICAL CO.,LTD
Contact:86-22-25814570
Address:No.12th,5th Ave.,TEDA,Tianjin,China
Zibo Ocean International Trade Co.,Ltd
Contact:+86 533 5160706
Address:1117, Hongtai Bld., Songling rd, Zichuan,Zibo,Shandong,China
Hangzhou Gangjin Chemical Co.,Ltd.
Contact:+86-571-85109780
Address:707 Zhejiang Minhang Bldg., No.290 Zhongshan North Road, Hangzhou 310003, China
JinTan Pingsheng Chemical Co.,Ltd
Contact:+86-519-82828200
Address:NO.11Danfengxilu Road,Jintan City,Jiangsu,China
Doi:10.1055/S-0029-1218614
(2010)Doi:10.1016/S0277-5387(02)00864-1
(2002)Doi:10.1016/S0040-4039(02)00403-3
(2002)Doi:10.1021/om0201563
(2002)Doi:10.1016/S0022-328X(01)01403-6
(2002)Doi:10.1248/cpb.c12-00916
(2013)