Light effect on the stability of β-lapachone in solution: pathways and kinetics of degradation

The purpose of this work was to study the chemical stability of the new antitumoral β-lapachone (βLAP) to determine the degradation pathway/s of the molecule and the degradation kinetics in addition to identifying several degradation products.

Samples of βLAP in solution were stored under conditions of darkness and illumination at 40°C at which the pseudo-first order rate constants for the βLAP 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.

The results revealed that βLAP shows two different degradation routes: hydrolysis in the dark and photolysis under the light. The βLAP exposure 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.

This study provides useful information for the development of βLAP dosage forms, their storage, manipulation and quality control.