Synthesis And Stability Study In Vitro On Two Compounds By Protecting Catechol Of Levodopa

Objective:Using two different methods to protect catechol of levodopa, The chemical and enzymatic stability of both was evaluated, in order to compare the impact of different protection on the drug stability.Methods:Methy1-2-amino-3-(spiro[benzo[d][1,3]dioxole-2,1’-cy-clohexan]-5-y1)propanoate hydrochloride (compounds3) and4-(2-ami-no-3-methoxy-3-oxopropyl)-1,2-phenylene diacetate hydrochloride(com-pounds4) was synthesized with Levodopa as the starting material. The structures of the compound3and compound4were confirmed by MS and1H-NMR. HPLC methods had been developed and validated for compound3and compound4. Chemical stability of compound3and compound4was studied at37.5℃in buffers(PH=1.3,5.0,7.4), samples were withdrawn in appropriate time and immediately analyzed by HPLC,in order to evaluate their chemical stability.PBS was used as blank control, The enzymatic stability of compound3and compound4was evaluated in human plasma at37.5℃, PH=7.4。Results:Compounds3and compounds4was synthesized with different methods.,the products are while with a purity exceeding95%. The structures of the compound3and compound4was confirmed by MS and1H-NMR.Compound3is more stable at the PH=1.3, and the worst stability at the pH=7.4, Compound4is more stable at the PH=5.0, and the worst stability at the pH=7.4.At the pH=1.3, the compound3was more stable compared to compound4.At the pH=5.0, compound4is more stable compared to compound3, At the pH=7.4, the degradation of compound4is slower than compound3. But compound3is more stable than compound4in human plasma.Conclusion:In the contrast of the stability of compound3and compound4, compound3showed a high stability and slow degradation in the human plasma. It can extend the degradation time of the drug. Therefore,the catechol was derived as Acetonide is more advantageous than derived as ester in extending the degradation time of the drug.