@conference{
author = "Đajić, Nevena and Krmar, Jovana and Otašević, Biljana and Malenović, Anđelija and Protić, Ana",
year = "2021",
abstract = "Introduction: Cyclodextrin (CD) added to RPHPLC
mobile phase interacts with analytes,
solvent components and stationary phase surface.
Therefore, the retention is influenced by the
analyte’s distribution between CD dissolved in the
mobile phase, free CD and formed inclusion
complex adsorbed onto the stationary phase, and
stationary phase itself (1, 2). The research goal
was to reveal the structural characteristics affecting
the inclusion complexation and retention in these
kinds of chromatographic systems by employing
QSRR-ANN models. Materials and Methods: Mixed QSRR model
included large pool of molecular descriptors,
complex association constants and experimental
parameters towards the retention factor of
risperidone, olanzapine and structurally related
impurities. The experimental space was
adequately covered with central composite design,
while experiments were conducted on Dionex
Ultimate 3000 (U) HPLC. QSRR-ANN modelling
was performed in STATISTICA Neural Networks.
Results: To evaluate the individual influence of
each of the descriptors, the difference in the
highest and lowest retention factor value across
the investigated range of the descriptor’s values
was calculated. The highest ratios were associated
with the following descriptors RDF075m, UE,
Mor04v and CATS2D_08_PL, making them the
most contributing towards the selected output.
RDF075m descriptor shows the three-dimensional
mass distribution calculated at a distance of 7.5 Å
from the geometrical centre of the molecule and it
refers to steric factors at the same distance.
Groups approximately 7.5 Å distant from the
geometrical centre of risperidone, olanzapine and
related compounds in their optimized
conformations were determined. These groups
were the same ones involved in the complexation
process according to previously performed NMR
study. Identified groups and their steric factors are
the most important for the formation of inclusion
complexes, and, in this way, the value of RDF075m
contributes to the retention of the selected
compounds. The importance of Mor04v confirms
the influence of molecular size and shape in
retention in these kinds of chromatographic
systems, while CATS2D_08_PL accounts for
lipophilicity.
Conclusions: The current study resulted in
development of QSRR-ANN with remarkable
performances, which enabled the elucidation of the
molecular features significantly influencing the
retention in β-CD-modified RP-HPLC. The
pronounced effect of molecular structure on
retention was best described through RDF075m,
followed by UE, Mor04v and CATS2D_08_PL.
Retention behaviour is also highly affected by
molecular size and shape, as well as lipophilicity of
the investigated compounds. Moreover, the size
and polarity of the chosen CD should not be
neglected, due to the consequent structural fit.",
publisher = "Ankara University Faculty of Pharmacy",
journal = "The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event",
title = "QSRR-ANN modelling in β-CD-modified RP-HPLC",
pages = "104-105",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4694"
}