Mechanism of the photochemical degradation of amlodipine

A mechanistic investigation on the photodegradation of amlodipine, the corresponding besylate and a simple analogue lacking the β-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 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 (ɛUV-A), despite the low quantum yield. Some comments are added about the fact that product Φ × ɛUV-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.