Abstract
The compound CWJ-a-5 [1-(4-methylpiperazinyl)-3-phenylisoquinoline hydrochloride] is a novel 3-arylisoquinoline derivative which has exhibited potent antitumor activity. As part of an effort to develop a useful formulation for clinical evaluation of this compound, the aqueous stability of CWJ-a-5 as a function of pH, ionic strength, and temperature, as well as its various physicochemical properties, have been examined. The pKa value obtained by potentiometric titration in methanol-water mixtures was 3.61, at 25°C. The aqueous solubility and the apparent partition coefficient of CWJ-a-5 over the pH range 2.08-9.88 were consistent with those expected of a weak acid of similar pKa value. The degradation of CWJ-a-5 was found to follow apparent first-order kinetics. The pH-rate profiles generated at 80°C were accounted for by acid-catalyzed degradation at low pH and base-catalyzed degradation at high pH. The activation energy was determined as 22.12 kcal/mol for the degradation of CWJ-a-5 in a pH2.92 solution with a constant ionic strength of 0.2. Increasing the ionic strength up to 0.9 led to a higher degradation rate constant at pH2.92. However, CWJ-a-5 was very stable even in a pH2.92 solution, and its shelf-life was calculated to be 2.03 years at 25°C from the Arrhenius plot.
Original language | English |
---|---|
Pages (from-to) | 889-895 |
Number of pages | 7 |
Journal | Drug Development and Industrial Pharmacy |
Volume | 28 |
Issue number | 7 |
DOIs | |
Publication status | Published - 2002 |
Externally published | Yes |
Keywords
- Antitumor
- CWJ-a-5
- Isoquinolone
- Physicochemical
ASJC Scopus subject areas
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry