Mechanism of the photochemical degradation of amlodipine.
A mechanistic investigation on the photodegradation of amlodipine, the corresponding besylate and a simple analogue lacking the beta-aminoethoxy group has been carried out in water and in organic solvents. Irradiation leads to aromatization to the corresponding pyridines through an oxygen-independent process. The quantum yield for amlodipine base is Phi congruent with 0.001 under UV-A light, about one order of magnitude larger than that for the model bearing no amino group, supporting intramolecular assistance by that group. The value of Phi increases up to ca. 0.01 at shorter wavelength. The photolability of this drug according to ICH criteria is justified by the high absorptivity in the UV-A range (epsilon(UV-A)), despite the low quantum yield. Some comments are added about the fact that product Phi x epsilon(UV-A) is more significative than Phi alone for the photolability (in solution) and about the lacking possibility to quench the photoreactivity where, as in the present case, this involves only short-lived intermediates.
Fasani
Elisa
E
Department of Organic Chemistry, University of Pavia, v. Taramelli 10, 27100 Pavia, Italy. elisa.fasani@unipv.it
Albini
Angelo
A
Gemme
Silvia
S
D017311:Amlodipine / Q000737:chemistry / Q000528:radiation effects*; D002121:Calcium Channel Blockers / Q000737:chemistry / Q000528:radiation effects*; D004355:Drug Stability; D008956:Models, Chemical; D015394:Molecular Structure; D010782:Photolysis; D012997:Solvents / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
D002121:Calcium Channel Blockers; D012997:Solvents; D014867:Water; D017311:Amlodipine