Photodegradation

Photodegradation has been reported for a large number of drug substances. The mechanisms for these reactions are generally very complex. As exemplified by chloro-quine207 and primaquine,208 shown in Schemes 53 and 54, respectively, photodegradation

Scheme 53. Photodegradation of chloroquine (R, and R2 are unknown).

Scheme 54. Photodegradation of primaquine.

Scheme 54. Photodegradation of primaquine.

generally yields numerous products through complex pathways. Photodegradation is often accompanied by oxidation in the presence of oxygen. Thus, drug substances such as fumagillin,209 210 phenothiazines,211 and cholecalciferol,192 whose oxidation was described in the previous section, are degraded to different products in the presence and absence of light.

Representative photodegradation routes for drug substances include dehydrogenation of nifedipine,212-214 reserpine,215 and nicardipine216 (Scheme 55); dehydrogenation accompanied by transmutation of a nitro group in nimodipine217 (Scheme 56); oxidation of a reactive methylene group to a carbonyl in 4-methoxy-2-(3-phenyI-2-propynyl)phenol (CO/1828),218 tiaprofenic acid,219 and KBT-3022 (a derivative of diphenylthiazole)220 221 (Scheme 57); and rearrangement of chlordiazepoxide222 (Scheme 58).

In addition, the following photoinduced degradation reactions have been reported: hydrolysis of mefloquine,223 furosemide,224 and LY277359 (a derivative of benzofuran carboxamide)225 (Scheme 59); elimination of hydrogen halide from meclofenamic acid226 (Scheme 60); oxidation of a hydroxyl group of 2 l-cortisol tert-butylacetate227 and a-[(dibutylamino)methy1]-6,8-dichloro-2-(3',4'-dichlorophenyl)-4-quinoline methanol228 (Scheme 61); and rearrangement of benzydamine229 (Scheme 62). Oxidation of menadione is enhanced by light (Scheme 63).230

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