Table III

Degradation Situations That Can Affect the Safety of Drug Products

TetracyclineEpimerization under acidic conditions forms anhydrotetracycline and 4-epitetracyclineReversible Fanconi syndrome(71, 72)
Meropenem (solution)Alkaline conditions and thermal degradation may yield 4-methyl-3- (1H-pyrrol-3-ylsulfanyl)-5H-pyrrole-2-carboxylic acid and other degradantsHigh concentrations of degraded samples demonstrate in vitro cytotoxic activity in mononuclear cells after 48h(73)
ChloramphenicolPhoto-oxidationInhibition of antibiotic activity(74)
IsoniazidHydrolytic degradation at high temperatures forms hydrazineGenotoxicity and carcinogenicity in animal models(75, 32)
IbuprofenOxidation and photodegradation can result in the generation of 1-(4-isobutylphenyl)-1-ethanolCytotoxicity to fibroblasts at concentrations above 1mM(76, 77)
Ascorbic acidDehydration and hydrolysis under anaerobic conditions may yield furfuralHepatotoxity in rats(78)
Enalapril maleate (tablets)High temperature and humidity can form enalaprilat and a diketopiperazine derivativeChange in the dissolution profile, impairment of drug bioavailability and decrease in the effectiveness(79)
PethidineHydrolytic degradation of an ester group can generate N-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP)Severe and irreversible symptoms of Parkinson's disease(80)
LidocaineHydrolytic degradation generates 2.6-xylidineAnoxia and damage to the hematopoietic system(8183)
GabapentinIntramolecular cyclization can form the β-lactam 3,3-pentamethylene-4-butyrolactam(2-azaspiro[4,5]decan-3-one)Induction of seizures in animal models(84)