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-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.
Registro:
Documento: |
Artículo
|
Título: | Isolation and structural elucidation of degradation products of alprazolam: Photostability studies of alprazolam tablets |
Autor: | Nudelman, N.S.; Cabrera, C.G. |
Filiación: | Depto. Química Orgánica, Facultad de Ciencias Exactas y Naturales, P.3 Ciudad Universitaria, 1428 Buenos Aires, Argentina
|
Palabras clave: | Alprazolam; Alprazolam photodegradation products; Alprazolam stability; Photochemical degradation; Triazolobenzodiazepines; alprazolam; aminoquinoline derivative; benzodiazepine derivative; benzophenone derivative; article; chemical reaction kinetics; drug degradation; drug isolation; drug stability; drug storage; hydrolysis; pH; photochemistry; structure analysis; tablet; thermostability |
Año: | 2002
|
Volumen: | 91
|
Número: | 5
|
Página de inicio: | 1274
|
Página de fin: | 1286
|
DOI: |
http://dx.doi.org/10.1002/jps.10141 |
Título revista: | Journal of Pharmaceutical Sciences
|
Título revista abreviado: | J. Pharm. Sci.
|
ISSN: | 00223549
|
CODEN: | JPMSA
|
CAS: | alprazolam, 28981-97-7
|
Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00223549_v91_n5_p1274_Nudelman |
Referencias:
- 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
Citas:
---------- APA ----------
Nudelman, N.S. & Cabrera, C.G.
(2002)
. Isolation and structural elucidation of degradation products of alprazolam: Photostability studies of alprazolam tablets. Journal of Pharmaceutical Sciences, 91(5), 1274-1286.
http://dx.doi.org/10.1002/jps.10141---------- CHICAGO ----------
Nudelman, N.S., Cabrera, C.G.
"Isolation and structural elucidation of degradation products of alprazolam: Photostability studies of alprazolam tablets"
. Journal of Pharmaceutical Sciences 91, no. 5
(2002) : 1274-1286.
http://dx.doi.org/10.1002/jps.10141---------- MLA ----------
Nudelman, N.S., Cabrera, C.G.
"Isolation and structural elucidation of degradation products of alprazolam: Photostability studies of alprazolam tablets"
. Journal of Pharmaceutical Sciences, vol. 91, no. 5, 2002, pp. 1274-1286.
http://dx.doi.org/10.1002/jps.10141---------- VANCOUVER ----------
Nudelman, N.S., Cabrera, C.G. Isolation and structural elucidation of degradation products of alprazolam: Photostability studies of alprazolam tablets. J. Pharm. Sci. 2002;91(5):1274-1286.
http://dx.doi.org/10.1002/jps.10141