Assessment of lisdexamfetamine dimesylate stability and identification of its degradation product by NMR spectroscopy.

Assessment of lisdexamfetamine dimesylate stability and identification of its degradation product by NMR spectroscopy. Drug Dev Ind Pharm. 2018 Sep 20;:1-21 Authors: Carlos G, Magalhães A, Isler AC, Comiran E, Fröehlich PE Abstract Lisdexamfetamine dimesylate (LDX), a long-acting prodrug stimulant indicated for the treatment of the attention-deficit/hyperactivity disorder (ADHD), was subjected to forced degradation studies by acid and alkaline hydrolysis and the degradation profile was studied. To obtain between 10-30% of degraded product, acid and alkaline conditions were assessed with solutions of 0.01 M, 0.1 M, 0.5 M and 1 M of DCl and NaOD. These solutions were analyzed through 1H NMR spectra. Acid hydrolysis produced no degradation in 0.01 M and 0.1 M DCl and 4.38%, 9.69% and 17.75% of degradation LDX, respectively, in 0.5 M, 1 M (4h) and 1 M (4 + 12 h) DCl. And alkaline hydrolysis produced no degradation in 0.01 M and 0.1 M DCl and a degradation LDX extension of 8.5%, 14.30% and 22.91%, respectively, in 0.5 M, 1 M (4h) and 1 M (4 + 12 h) NaOD. LDX solutions subjected to 1M (4 + 12 h) acid and alkaline hydrolysis were evaluated by NMR spectra (1H NMR, 13C NMR, HSQC and HMBC). LDX degradation product (DP) was identified and its structure elucidated as a diastereoisomer of LDX: (2R)-2,6-diamino-N-[(2S)-1-phenylpropan-2-yl] hexanamide without their physical separation. PMID: 30231652 [PubMed - as supplied by pu...
Source: Drug Development and Industrial Pharmacy - Category: Drugs & Pharmacology Tags: Drug Dev Ind Pharm Source Type: research