Light effect on the stability of ß-lapachone in solution: Pathways and kinetics of degradation

Abstract

Objectives The purpose of this work was to study the chemical stability of the new antitumoral b-lapachone (bLAP) to determine the degradation pathway/s of the molecule and the degradation kinetics in addition to identifying several degradation products. Method Samples of bLAP in solution were stored under conditions of darkness and illumination at 40°C at which the pseudo-first order rate constants for the bLAP degradation were determined. Furthermore, drug degraded solutions were concentrated and purified using Sephadex LH-20 and preparative thin-layer chromatography and degradation products were identified by nuclear magnetic resonance spectroscopy. Key findings The results revealed that bLAP shows two different degradation routes: hydrolysis in the dark and photolysis under the light. The bLAPexposure to light accelerated the drug degradation about 140 fold, compared with the samples stored in the absence of light. The hydrolysis produced hydroxylapachol as the main degradation product. The photolysis yielded phthalic acid, 6-hydroxy-3methylene-3H-isobenzofuran-1-one and a benzomacrolactone together with a complex mixture of other phthalate-derivatives such as 2-(2-carboxy-acetyl)-benzoic acid. Conclusions This study provides useful information for the development of bLAP dosage forms, their storage, manipulation and quality control.