DEGRADATION PROFILE AND IDENTIFICATION OF THE MAJOR DEGRADATION PRODUCTS OF DOBUPRIDE UNDER SEVERAL CONDITIONS BY GC MS AND HPLC-PARTICLE BEAM MS/

The effect of pH, light, temperature and oxygen on the stability of do bupride (1), a novel gastroprokinetic drug, has been studied, storing the sample in the solid state and as a solution in methanol-water. The main forced degradation products have been identified by means of tec hniques such as GC/MS and HPLC-particle beam/MS, and two major degrada tion pathways have been characterized. One degradation route involves the loss of chlorine, yielding [1-(1,3-dioxolan-2-ylmethyl)piperid-4-y l]benzamide (4) as the major degradation product. The second pathway r esults from cleavage of the piperidine-amide bond, producing 4-amino-2 -butoxy-5-chlorobenzamide (2) as the major degradation product. Under the studied conditions, except when exposed to direct light in solutio n, dobupride has been shown to be very stable: after 5 months storage, the benzamide 2 (second pathway) was the only product identified (les s than 0.5%). However, when dobupride in solution is exposed to natura l or artificial sunlight, degradation is very fast, and after 7 days o nly 5% of the unchanged product remains. Under these circumstances, th e main degradation route is the first one, with compound 4 being the m ost abundant degradation product, and compound 2 only being detectable in small amounts.