title: Isolation and structural elucidation of degradation products of alprazolam: photostability studies of alprazolam tablets.
abstract: Accelerated thermal, hydrolytic, and photochemical degradations of alprazolam were performed under several reaction conditions. The stress studies revealed the photolability of the drug as the most adverse stability factor; the main photodegradation products were isolated and properly characterized as: triazolaminoquinoleine; 5-chloro-[5"-methyl-4H-1,2,4-triazol-4-yl]benzophenone, and 1-methyl-6-phenyl-4H-s-triazo-[4,3-alpha][1,4]benzodiazepinone. Accelerated pH-dependent studies show that the photoinstability increases as the pH decreases; at pH 9.0, photodegradation does not occur, therefore, the photochemical degradation of alprazolam was performed in buffered solutions at pH 2.0 and 3.6. The higher rate of reaction was observed at pH = 2.0; consequently, acidic conditions should be avoided and appropriate light protection is recommended during the drug-development process, storage, and handling. The main degradation route for alprazolam tablets is also photochemical.
authors.affiliation: Depto. Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Pab. II, P.3 Ciudad Universitaria, 1428 Buenos Aires, Argentina. nudelman@qo.fcen.uba.ar
authors.forename: Norma S
authors.initials: NS
authors.lastname: Nudelman
authors.forename: C Gallardo
authors.initials: CG
authors.lastname: Cabrera
mesh_terms: D000525:Alprazolam / Q000737:chemistry* / Q000528:radiation effects; D014151:Anti-Anxiety Agents / Q000737:chemistry* / Q000528:radiation effects; D001569:Benzodiazepines / Q000737:chemistry*; D001577:Benzophenones / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D008027:Light; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010777:Photochemistry; D011804:Quinolines / Q000737:chemistry*; D013607:Tablets
chemical_list: C465920:1-methyl-6-phenyl-4H-s-triazo-(4,3-alpha)(1,4)benzodiazepinone; C465921:5-chloro-(5''-methyl-4H-1,2,4-triazol-4-yl)benzophenone; D014151:Anti-Anxiety Agents; D001577:Benzophenones; D011804:Quinolines; D013607:Tablets; C465922:triazolaminoquinoleine; D001569:Benzodiazepines; D000525:Alprazolam