Stability of Drugs and Dosage Forms Sumie Yoshioka

44 Chapter 2 • Chemical Stability of Drug Substances
Scheme 68. Consecutive loss of carbamate groups in carmethizole (NSC-602668). The reactivity of one
carbamate group is greater than that of the other. (Reproduced from Ref. 46 with permission.)
(2.30)
A good example of consecutive reactions is the degradation of carmethizole (NSC-602668), an
experimental cytotoxic agent (Scheme 68). 44 The hydrolysis of hydrocortisone hemisuccinate
(Fig. 11) 30 and alkaline epimerization followed by hydrolysis of etoposide (Fig. 12) 156,157 fit this
mathematical model even though their degradation pathways are more complex.
2.2.3.1.g.
Pseudo-First-Order Reversible and Consecutive Reactions
When drug D is reversibly converted to P 1 , which is reversibly converted to P 2 by
apparent first-order kinetics, Equations (2.31) and (2.32) represent the rate and integrated
expressions, respectively.
Figure 11. Time course of hydrolysis of hydrocortisone hemisuccinate (pH 6.9, 70°C). (Reproduced from Ref.
30 with permission.)