Available online at www.sciencedirect.com
Journal of Pharmaceutical and Biomedical Analysis 46 (2008) 597–602
Short communication
Application of a self-modeling curve resolution method for studying the
photodegradation kinetics of nitrendipine and felodipine
Katayoun Javidnia
a
, Bahram Hemmateenejad
a,b,∗
,
Ramin Miri
a
, Mehdi Saeidi-Boroujeni
a
a
Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences, Shiraz 71345, Iran
b
Department of Chemistry, Shiraz University, Shiraz 71454, Iran
Received 15 September 2007; received in revised form 5 November 2007; accepted 12 November 2007
Available online 22 November 2007
Abstract
Dihydropyridine (DHP) derivatives, as calcium channel blockers with cardiovascular activity, are highly photosensitive and converted in the
presence of light to compounds that are inactive. In this work, a self-modeling curve resolution method was applied to study the photodegradation
kinetics of nitrendipine and felodipine by spectrophotometric method. The methanolic solutions of drugs were separately exposed to UV and
daylight, respectively. A fully soft-modeling multivariate curve resolution method based on the combination of iterative target transformation and
Kubista methods were used to analyze the recorded absorbance data, extracting the concentration profiles and pure spectra of the drugs and their
photodegradation products. By fitting the concentration profiles of the studied DHP drugs to different kinetic equations, it was found that at the
beginning of lighting, the reaction is zero-order and in the case of nitrendipine it changes to a first-order kinetic when the concentration of products
exceeded than that of the initial compounds.
© 2007 Elsevier B.V. All rights reserved.
Keywords: Photodegradation; Multivariate curve resolution; Nitrendipine; Felodipine
1. Introduction
Nitrendipine, 4-(3-nitrophenyl)-1,4-dihydro-2,6-dimethylp-
yridine-3,5-dicarboxylate and felodipine, 4-(2,3-dichloro-
phenyl)-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate
(see Fig. 1), are calcium channel antagonists of dihydropyridine
(DHP) class used in the treatment of hypertension [1–3].
DHP derivatives are highly photosensitive and converted in
the presence of light to compounds that are inactive, and the
most of the methods used for these studies were different
chromatographic methods [4–12]. Of course chromatographic
methods are difficult to operate and use relatively expensive
instruments. In addition, further degradation of drugs may
occur during the chromatographic analysis.
In the other hand, spectrophotometric methods are in gen-
eral simple, sensitive and very suitable for studying chemical
∗
Corresponding author at: Department of Chemistry, Shiraz University,
Adabiat Four-way, Shiraz, Fars 71454, Iran. Tel.: +98 711 2284822;
fax: +98 711 2286008.
E-mail address: hemmatb@sums.ac.ir (B. Hemmateenejad).
reactions in solutions. The spectral overlapping, as the major
problem in almost all of the spectrochemical methods, can be
overcome utilizing different chemometric methods [13]. For
example, spectral curve deconvolution or multivariate curve
resolution (MCR) methods are chemometrics techniques con-
cerning with the extraction of the pure spectra and concentration
profiles of the components in a chemical reaction preceded in an
evolutionary process [14–16]. There are some literature reports
on the use of different MCR methods for studying the forced
degradation kinetics of drugs and other biologically important
compounds [17,18].
In our research group, we have some interests on DHP deriva-
tives and many papers have been published from this group
regarding this type of molecules in different subjects [19–24].
We employed a constrained self-modeling MCR method for
monitoring the photodegradation kinetics of nifedipine, the pro-
totype of DHP drugs [25]. Since the photodegradation kinetic
of DHP-based drugs is complex and it is preceded in zero-
and first-order manners, application of hard-modeling methods
is not straightforward. Thus, we extend our previously self-
modeling method for studying the photodegradation monitoring
0731-7085/$ – see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jpba.2007.11.020