Mechanism of photochemical degradation of amlodipine

Amechanistic investigation on the photodegradation of amlodipine, the corresponding besylate and a simple analogue lacking the -aminoethoxy group has been carried out in water and in organic solvents. Irradiation leads to aromatization to the corresponding pyridines through an oxygenindependent process. The quantum yield for amlodipine base is Φ ∼= 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 Φ 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 (εUV-A), despite the low quantum yield. Some comments are added about the fact that product Φ×εUV-A is more significative than Φ 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.