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...

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Autor principal: Nudelman, N.S
Otros Autores: Cabrera, C.G
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: John Wiley and Sons Inc. 2002
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Acceso en línea:Registro en Scopus
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Sumario: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-α][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. © 2002 Wiley-Liss, Inc.
Bibliografía:Laihanen, N., Muttonen, E., Laaksonen, M., Solubility and intrinsic dissolution rate of alprazolam crystal modifications (1996) Pharm Dev Technol, 14, pp. 373-380
Dresser, G.K., Spence, J.D., Bailey, D.G., Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition (2000) Clin Pharmacokinet, 38 (1), pp. 41-57
Gommans, J., Hijzen, T.H., Maes, R.A., Olivier, B., Discriminative stimulus properties of alprazolam (2000) Psychopharmacology, 148 (2), pp. 146-152
Yuan, R., Flockhart, D.A., Balian, J.D., Pharmacokinetic and pharmacodynamic consequences of metabolism-based drug interactions with alprazolam, midazolam, and triazolam (1999) J Clin Pharmacol, 39 (11), pp. 1109-1125
Santagostino, G., Cucchi, M.L., Frattini, P., Zerbi, F., Di Paolo, E., Preda, S., Corona, G.L., The influence of alprazolam on the monoaminergic neurotransmitter systems in dysthymic patients: Relationship to clinical response (1998) Pharmacopsychiatry, 31 (4), pp. 131-136
Greenblatt, D.J., Javaid, J.I., Locniskar, A., Harmatz, J.S., Shader, R.I., Gas chromatographic analysis of alprazolam in plasma: Replicability, stability and specificity (1990) J Chromatogr, 534, pp. 202-207
Greenblatt, D.J., Divoll, M., Moschitto, L.J., Shader, R.I., Electron-capture gas chromatographic analysis of the triazolobenzodiazepines alprazolam and triazolam (1981) J Chromatogr, 225, pp. 202-207
Hall, M.A., Robinson, A., Brissie, R.M., High-performance liquid chromatography of alprazolam in postmortem blood using solid phase extraction (1995) J Anal Toxicol, 19, pp. 511-513
Schmith, V.D., Cox, S.R., Zemaitis, M.A., Kroboth, P.D., New high-performance liquid chromatographic method for the determination of alprazolam and its metabolites in serum: Instability of 4-hydroxyalprazolam (1991) J Chromatogr, 568, pp. 253-260
Hold, K.M., Crouch, D.J., Rollins, D.E., Wilkins, D.G., Maes, R.A., Detection of alprazolam in hair by negative ion chemical ionization mass spectrometry (1997) Forensic Sci Int, 84, pp. 201-209
Crouch, D.J., Rollins, D.E., Canfield, D.E., Andrenyak, D.M., Schulties, J.E., Quantitation of alprazolam and α-hydroxyalprazolam in human plasma using liquid chromatography electrospray ionization MS-MS (1999) J Anal Toxicol, 23, pp. 479-485
Hold, K.M., Rollins, D.E., Crouch, D.J., Wilkins, D.G., Canfield, D.V., Maes, R.A., Determination of alprazolam and α-hydroxyalprazolam in human plasma by gas chromatography/negative-ion chemical ionization mass spectrometry (1996) J Mass Spectrom, 31, pp. 1033-1038
Konishi, M., Hirai, K., Mori, Y., Kinetics and mechanism of the equilibrium reaction of triazolam in aqueous solution (1982) J Pharm Sci, 71, pp. 1328-1334
Andersin, R., Mesilaakso, M., Photochemical decomposition of midazolam. IV. Study of pH-dependent stability by high-performance liquid chromatography (1995) J Pharm Biomed Anal, 13, pp. 667-670
Cho, M.J., Scahill, T.A., Hester, J.B., Kinetics and equilibrium of the reversible alprazolam ring-opening reaction (1983) J Pharm Sci, 72, pp. 356-362
Nudelman, N.S., Waisbaum, R.G., Kinetic study of the reaction of 2-amino-5-chlorobenzophenone with HC1 in MeOH-H2O (1997) J Phys Org Chem, 10, pp. 97-106
Nudelman, N.S., Waisbaum, R.G., Isolation and structure elucidation of novel products of the acidic degradation of diazepam (1995) J Pharm Sci, 84, pp. 208-211
Nudelman, N.S., Waisbaum, R.G., Acid hydrolysis of diazepam: Kinetic study of the reactions of 2-(N-methylamino)-5-chlorobenzophenone, with HCl in MeOH-H2O (1995) J Pharm Sci, 84, pp. 998-1004. , and refs. therein
Nudelman, N.S., Gallardo, C., Factores que afectan estabilidad de alprazolam: Elucidación estructural de los principales productos de degradación (1999) Vitae, 6, pp. 29-40
Nudelman, N.S., Waisbaum, R.G., Gallardo, C., Stability studies of benzodiazepines: Solvolysis and photodegradation (1998) Atualidades Fisico Quim Org, pp. 478-497
Allen, L.E., Erickson, M.A., Stability of alprazolam, chloroquine phosphate, cisapride, enalapril maleate and hydralazine hydrochloride in extemporaneously compounded oral liquids (1998) Am J Health Syst Pharm, 55, pp. 1915-1920
Caira, M.R., Easter, B., Honiball, S., Horne, A., Nassimbeni, L.R., Structure and thermal stability of alprazolam and selected solvates (1995) J Pharm Sci, 84, pp. 1379-1384
Stemm, N.L., Skoug, J.W., Robins, R.H., Gradient high performance liquid chromatography assay for degradation products of adinazolam mesylate in a sustained release tablet formulation (1995) Pharm Res, 12, pp. 738-745
Kanwar, A.J., Gupta, R., Das Metha, S., Photosensitivity due to alprazolam (1990) Dermatologica, 181, p. 75
Harth, Y., Rapoport, M., Photosensitivity associated with antipsychotics, antidepressant and anxiolytics (1996) Drug Saf, 14, pp. 252-259
Reid, C.G., Photosensitivity: Not a picture of health (1995) Can Pharm J, 128, pp. 31-56
Tonnesen, H.H., Introduction: Photostability testing of drug formulations - Why and how? (1996) Photostability of drugs and drug formulations, pp. 1-7. , Tonnesen HH, editors. London: Taylor & Francis
Piechocki, J.T., Selecting the right source for pharmaceutical photostability testing (1998) Drugs: Photochemistry and photostability, pp. 247-271. , Albini A, Fasani E, editors. Cambridge: Royal Society of Chemistry
(1996) Photostability testing of new drug sustances and products, , November
(1997) Fed Regist, 62, p. 27115
(1998) Guidance for industry: Stability testing of drug substances and drug product, draft guidance, , June
Valvini, S.C., Industrial stability testing in the United States and computerization of stability data (2000) Drug stability, principles and practices, 3rd ed., pp. 515-552. , Carstensen JT, Rhodes CT, editors. New York: Marcel Dekker
Moore, D.E., Standardization of photodegradation studies and kinetic treatment of photochemical reaction (1996) Photostability of drugs and drug formulations, pp. 65-66. , Tonnesen HH, editor. London: Taylor & Francis
Hong, D.D., Shah, M., Development and validation of HPLC stability-indicating assays (2000) Drug stability, principles and practices, 3rd ed., pp. 329-384. , Carstensen JT, Rhodes CT, editors. New York: Marcel Dekker
Anderson, N.H., Photostability testing: Design and interpretation of tests on drug substances and dosage forms (1996) Photostability of drugs and drug formulations, pp. 305-321. , Tonnesen HH, editors. London: Taylor & Francis
Photostability testing (2000) Pharmacopeial Forum, 26, pp. 384-387
Cho, M.J., Sethy, V.H., Haynes, L.C., Sequentially labile water-soluble prodrugs of alprazolam (1986) J Med Chem, 29, pp. 1346-1350
Jimenez, R.M., Dominguez, E., Bahia, D., Alonso, R.M., Vicent, F., On the mechanism of hydrolysis of the triazolobenzodiazepine, triazolam, spectroscopic study (1987) J Heterocycl Chem, 24, p. 421
Greenhill, J.V., Is the photodecomposition of drugs predictable? (1996) Photostability of drugs and drug formulations, pp. 83-110. , Tonnesen HH, editor. London: Taylor & Francis
Moore, D.E., Roberts-Thomson, S., Zhen, D., Duke, C.C., Photochemical studies on the anti-inflammatory drug diclofenac (1990) Photochem Photobiol, 52, pp. 685-690
Schoonderwoerd, S.A., Beijerssbergen van Henegouwen, G.M., Van Belkum, S., In vivo photodegradation of chlorpromazine (1989) Photochem Photobiol, 50, p. 659
Greenhill, J.V., McLelland, M.A., Photodecomposition of drugs (1990) Progress in medicinal chemistry, 27, pp. 51-121. , Ellis GP, West GB, editors. Amsterdam: Elsevier
ISSN:00223549
DOI:10.1002/jps.10141