Isolation and structural elucidation of degradation products of alprazolam: photostability studies of alprazolam tablets.
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.
Nudelman
Norma S
NS
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
Cabrera
C Gallardo
CG
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
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