Spectroscopic and HPLC Studies of Photodegradation of Nilvadipine

Abstract

Photochemical decomposition of nilvadipine (NV), a derivative of 1,4-dihydropyridine (DHP), was studied. Photodegradation was carried out in the conditions recommended in the first version of the document issued by the International Conference on Harmonization (ICH), currently in force in the studies of photochemical stability of drugs and therapeutic substances. Methanol solutions of NV were irradiated with a high-pressure mercury arc lamp, type HBO 200 (300–400 nm). The maximum absorption of radiation at 365 nm was achieved by applying the interference filter and Wood's filter. The assessment of NV photodegradation was made on the basis of the UV spectrophotometric and high-performance liquid chromatographic (HPLC) methods. Quantitatively, the process was described with the calculated rate constants of decomposition k, time of decomposition of 50% of the compound t_0.5, and time of decomposition of 10% of the compound t_0.1. The two methods applied allowed a determination of the kinetic parameters of NV photodegradation from the relationship ln c = f(t). Using the Reinecke salt as a chemical actinometer, apparent quantum yields of photodegradation were obtained; after extrapolation to the time of irradiation zero, these gave the actual quantum yield (Φ = 7.3 · 10⁻⁵). The quantum yield of fluorescence at λ_exc = 375 nm was about 9.3 · 10⁻⁴. The methods used for evaluation of NV photodegradation were subjected to validation, and results of the analytical methods were statistically assessed by Snedecor F and Student t tests. The former test revealed no statistically significant difference between the variances obtained by the HPLC and UV spectrophotometric methods. Also, verification of the zero hypothesis of the Student t test on equality of means of the results obtained gave no significant differences between the two methods.

Key Words:

• 1.4-Dihydropyridine derivatives
• Nilvadipine
• Photodegradation
• Validation