Physicochemical properties of CWJ-a-5, a new antitumor 3-arylisoquinoline derivative.
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 degrees 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 degrees 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 pH 2.92 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 pH 2.92. However, CWJ-a-5 was very stable even in a pH 2.92 solution, and its shelf-life was calculated to be 2.03 years at 25 degrees C from the Arrhenius plot.
Kim
Ki-Eun
KE
College of Pharmacy, Pusan National University, Pusan 609-735, South Korea.
Cho
Won-Jea
WJ
Kim
Tae-Sung
TS
Kang
Boo-Hyon
BH
Chang
Sun-Jae
SJ
Lee
Chi-Ho
CH
Kim
Dae-Duk
DD
D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007546:Isoquinolines / Q000737:chemistry*; D012995:Solubility
C428783:CWJ-a-5; D007546:Isoquinolines