Kinetics of chlorambucil hydrolysis using high-pressure liquid chromatography.

Abstract:

:A stability-specific high-pressure liquid chromatographic (HPLC) method was developed to assay intact chlorambucil (I) in the presence of its hydrolytic decomposition products. The HPLC method was used to follow the degradation kinetics of I over pH 1.0-10.0 in the presence of various buffers with and without added chloride ion. In the absence of chloride ion, the hydrolysis of I followed first-order kinetics and the pH rate profile showed a sharp inflection around pH 2.5 attributable to the ionization of the nitrogen mustard and a shallower inflection around pH 5.0 attributable to the ionization of the carboxylic group. The rate was pH independent over pH 6.0-10.0 and independent of buffer species in the absence of chloride ion. IN the presence of chloride ion, the kinetics of I hydrolysis was still first order. However, the degradation half-life at a particular pH and buffer concentration increased linearly with chloride concentration. Kinetic evidence is presented to show that the mechanism of chloride stabilization involves the attack of chloride ion on the unstable cyclic ethyleneimmonium intermediate to give back I. Implications of the kinetic data obtained on the fate of orally administered I are discussed.

journal_name

J Pharm Sci

authors

Chatterji DC,Yeager RL,Gallelli JF

doi

10.1002/jps.2600710113

subject

Has Abstract

pub_date

1982-01-01 00:00:00

pages

50-4

issue

1

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)44019-5

journal_volume

71

pub_type

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