Autoxidation of tetrazepam in tablets: prediction of degradation impurities from the oxidative behavior in solution.

Abstract:

:The major route of degradation of tetrazepam (1) is oxidation to 7-chloro-5-(3-keto-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2-one (3) via the stable 7-chloro-5-(3-hydroperoxy-cyclohexen-1-yl)-1,3-dihydro-1-methyl-2H -1, 4 benzodiazepin-2-one (2). Minor degradation products are 7-chloro-5-(1,2-epoxycyclohexan-1-yl)-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2-one (5) and 7-chloro-1,3-dihydro-1-methyl-2H-1, 4-benzodiazepin-2,5-dione (4), resulting from cleavage of the C-C bond between the cyclohexene ring and the benzodiazepine ring. After 48 h, AIBN (2,2'-azobis[2-methyl-propanenitrile]) in acetonitrile at 40 degrees C produced qualitatively the same impurities as those observed in the stability study of tablets of 1. Other stress tests (thermal stress at 80 degrees C, heavy metal oxidation, hydrogen peroxide, acid-catalyzed oxidation) caused qualitatively different profiles of degradation.

journal_name

J Pharm Sci

authors

Boccardi G,Deleuze C,Gachon M,Palmisano G,Vergnaud JP

doi

10.1002/jps.2600810216

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

183-5

issue

2

eissn

0022-3549

issn

1520-6017

pii

S0022-3549(15)48746-5

journal_volume

81

pub_type

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