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

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 1 H 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 1 M (4 + 12 h) acid and alkaline hydrolysis were evaluated by NMR spectra (1 H NMR, 13 C 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.

Determinação quantitativa de taninos em três espécies de stryphnodendron por cromatografia líquida de alta eficiência / Quantitative determination of tannins in three species of stryphnodendron by high performance liquid chromatography

Um método de separação e quantificação por cromatografia líquida de alta eficiência (CLAE) em fase reversa foi desenvolvido usando água (0,05 por cento de TFA):acetonitrila (0,05 por cento de TFA) como fase móvel, em sistema gradiente para a análise dos flavan-3-óis presentes em extrato semipurificado das cascas de Stryphnodendron adstringens, Stryphnodendron polyphyllum e Stryphnodendron obovatum. A CLAE foi realizada com a fração acetato de etila (FAE) sendo submetida à extração em fase sólida (cartucho C18-E) com metanol:água (2:8), filtrada por membrana de porosidade 0,5 μm; a pré-coluna e coluna empregadas foram Phenomenex® Gemini C-18 (5 μm), com esta última mantida a 30 ºC, com vazão de 0,8 mL/min e detecção a 210 nm. Utilizaram-se soluções dos padrões de ácido gálico e galocatequina para a obtenção da curva analítica. O método proposto foi validado de acordo com a resolução RE nº 899/2003 da ANVISA. A análise quantitativa da FAE das três espécies mostrou que existe similaridade no teor de galocatequina. S. adstringens possui ácido gálico em uma proporção superior a 60 por cento em relação às outras duas espécies. A metodologia desenvolvida mostrou-se viável à aplicação em plantas ricas em taninos, como nos casos de S. adstringens, S. polyphyllum e S. obovatum.

A method of separation and quantification by reverse-phase high-performance liquid chromatography (HPLC) was developed, using water (0.05 percent TFA):acetonitrile (0.05 percent TFA) as the mobile phase in a gradient system. Flavan-3-ols present in a semipurified extract from the stem bark of Stryphnodendron adstringens, Stryphnodendron polyphyllum and Stryphnodendron obovatum were analyzed. The HPLC was performed with the ethyl-acetate fraction (EAF) using a solid-phase extraction on cartridges C18-E with methanol:water (2:8), filtered through a membrane of 0.5 μm pore size; the column was Phenomenex® Gemini C-18 (5 μm) at 30 ºC, with a flow rate of 0.8 mL/min. The analysis was done at 210 nm. Gallic acid and gallocatechin solutions were used as calibration standards. The proposed method was validated by resolution RE No. 899/2003 of the National Health Surveillance Agency. Quantitative analysis of the EAF showed high contents of flavan-3-ols in the stem bark of all three species. This study demonstrated that it is possible to determine the concentration of individual substances in tannin-rich plants. The system developed can be used as a chromatographic profile for the semipurified fraction of S. adstringens, S. polyphyllum, and S. obovatum.