QSRR-ANN modelling in β-CD-modified RP-HPLC
Апстракт
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 Netw...orks.
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.
Извор:
The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event, 2021, 104-105Издавач:
- Ankara University Faculty of Pharmacy
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
Напомена:
- ISOPS 13, Abstract Book
Институција/група
PharmacyTY - CONF AU - Đajić, Nevena AU - Krmar, Jovana AU - Otašević, Biljana AU - Malenović, Anđelija AU - Protić, Ana PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4694 AB - 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. PB - Ankara University Faculty of Pharmacy C3 - The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event T1 - QSRR-ANN modelling in β-CD-modified RP-HPLC SP - 104 EP - 105 UR - https://hdl.handle.net/21.15107/rcub_farfar_4694 ER -
@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" }
Đajić, N., Krmar, J., Otašević, B., Malenović, A.,& Protić, A.. (2021). QSRR-ANN modelling in β-CD-modified RP-HPLC. in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event Ankara University Faculty of Pharmacy., 104-105. https://hdl.handle.net/21.15107/rcub_farfar_4694
Đajić N, Krmar J, Otašević B, Malenović A, Protić A. QSRR-ANN modelling in β-CD-modified RP-HPLC. in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event. 2021;:104-105. https://hdl.handle.net/21.15107/rcub_farfar_4694 .
Đajić, Nevena, Krmar, Jovana, Otašević, Biljana, Malenović, Anđelija, Protić, Ana, "QSRR-ANN modelling in β-CD-modified RP-HPLC" in The 13th International Symposium on Pharmaceutical Sciences, Ankara, Turkey, 22-25. June 2021, Virtual event (2021):104-105, https://hdl.handle.net/21.15107/rcub_farfar_4694 .