TY  - JOUR
AU  - Krmar, Jovana
AU  - Tolić Stojadinović, Ljiljana
AU  - Đurkić, Tatjana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2023
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6373
AB  - A priori estimation of analyte response is crucial for the efficient development of liquid chromatography–electrospray ionization/mass spectrometry (LC–ESI/MS) methods, but remains a demanding task given the lack of knowledge about the factors affecting the experimental outcome. In this research, we address the challenge of discovering the interactive relationship between signal response and structural properties, method parameters and solvent-related descriptors throughout an approach featuring quantitative structure–property relationship (QSPR) and design of experiments (DoE). To systematically investigate the experimental domain within which QSPR prediction should be undertaken, we varied LC and instrumental factors according to the Box-Behnken DoE scheme. Seven compounds, including aripiprazole and its impurities, were subjected to 57 different experimental conditions, resulting in 399 LC–ESI/MS data endpoints. To obtain a more standard distribution of the measured response, the peak areas were log-transformed before modeling. QSPR predictions were made using features selected by Genetic Algorithm (GA) and providing Gradient Boosted Trees (GBT) with training data. Proposed model showed satisfactory performance on test data with a RMSEP of 1.57 % and a of 96.48 %. This is the first QSPR study in LC–ESI/MS that provided a holistic overview of the analyte's response behavior across the experimental and chemical space. Since intramolecular electronic effects and molecular size were given great importance, the GA–GBT model improved the understanding of signal response generation of model compounds. It also highlighted the need to fine-tune the parameters affecting desolvation and droplet charging efficiency.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities
SP  - 115422
VL  - 233
DO  - 10.1016/j.jpba.2023.115422
ER  - 

@article{
author = "Krmar, Jovana and Tolić Stojadinović, Ljiljana and Đurkić, Tatjana and Protić, Ana and Otašević, Biljana",
year = "2023",
abstract = "A priori estimation of analyte response is crucial for the efficient development of liquid chromatography–electrospray ionization/mass spectrometry (LC–ESI/MS) methods, but remains a demanding task given the lack of knowledge about the factors affecting the experimental outcome. In this research, we address the challenge of discovering the interactive relationship between signal response and structural properties, method parameters and solvent-related descriptors throughout an approach featuring quantitative structure–property relationship (QSPR) and design of experiments (DoE). To systematically investigate the experimental domain within which QSPR prediction should be undertaken, we varied LC and instrumental factors according to the Box-Behnken DoE scheme. Seven compounds, including aripiprazole and its impurities, were subjected to 57 different experimental conditions, resulting in 399 LC–ESI/MS data endpoints. To obtain a more standard distribution of the measured response, the peak areas were log-transformed before modeling. QSPR predictions were made using features selected by Genetic Algorithm (GA) and providing Gradient Boosted Trees (GBT) with training data. Proposed model showed satisfactory performance on test data with a RMSEP of 1.57 % and a of 96.48 %. This is the first QSPR study in LC–ESI/MS that provided a holistic overview of the analyte's response behavior across the experimental and chemical space. Since intramolecular electronic effects and molecular size were given great importance, the GA–GBT model improved the understanding of signal response generation of model compounds. It also highlighted the need to fine-tune the parameters affecting desolvation and droplet charging efficiency.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities",
pages = "115422",
volume = "233",
doi = "10.1016/j.jpba.2023.115422"
}

Krmar, J., Tolić Stojadinović, L., Đurkić, T., Protić, A.,& Otašević, B.. (2023). Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 233, 115422.
https://doi.org/10.1016/j.jpba.2023.115422

Krmar J, Tolić Stojadinović L, Đurkić T, Protić A, Otašević B. Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities. in Journal of Pharmaceutical and Biomedical Analysis. 2023;233:115422.
doi:10.1016/j.jpba.2023.115422 .

Krmar, Jovana, Tolić Stojadinović, Ljiljana, Đurkić, Tatjana, Protić, Ana, Otašević, Biljana, "Predicting liquid chromatography−electrospray ionization/mass spectrometry signal from the structure of model compounds and experimental factors; case study of aripiprazole and its impurities" in Journal of Pharmaceutical and Biomedical Analysis, 233 (2023):115422,
https://doi.org/10.1016/j.jpba.2023.115422 . .

TY  - CONF
AU  - Krmar, Jovana
AU  - Tolić-Stojadinović, Ljiljana
AU  - Vukićević, Milan
AU  - Đurkić, Tatjana
AU  - Protić, Ana
AU  - Otašević, Biljana
PY  - 2022
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/6488
PB  - University of Mons (Belgium)
C3  - 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book
T1  - The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4691
ER  - 

@conference{
author = "Krmar, Jovana and Tolić-Stojadinović, Ljiljana and Vukićević, Milan and Đurkić, Tatjana and Protić, Ana and Otašević, Biljana",
year = "2022",
publisher = "University of Mons (Belgium)",
journal = "12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book",
title = "The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4691"
}

Krmar, J., Tolić-Stojadinović, L., Vukićević, M., Đurkić, T., Protić, A.,& Otašević, B.. (2022). The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?. in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book
University of Mons (Belgium)..
https://hdl.handle.net/21.15107/rcub_farfar_4691

Krmar J, Tolić-Stojadinović L, Vukićević M, Đurkić T, Protić A, Otašević B. The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?. in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_4691 .

Krmar, Jovana, Tolić-Stojadinović, Ljiljana, Vukićević, Milan, Đurkić, Tatjana, Protić, Ana, Otašević, Biljana, "The modern age of chemomometrics: What is the secret behind LC–ESI(+)/MS response generation?" in 12th International Symposium on Drug Analysis & 32nd International Symposium on Pharmaceutical and Biomedical Analysis, From 11th to 14th September 2022, Mons, Belgium, Abstract book (2022),
https://hdl.handle.net/21.15107/rcub_farfar_4691 .

TY  - JOUR
AU  - Kovačević, Strahinja
AU  - Karadžić Banjac, Milica
AU  - Milošević, Nataša
AU  - Ćurčić, Jelena
AU  - Marjanović, Dunja
AU  - Todorović, Nemanja
AU  - Krmar, Jovana
AU  - Podunavac-Kuzmanović, Sanja
AU  - Banjac, Nebojša
AU  - Ušćumlić, Gordana
PY  - 2020
UR  - http://TechnoRep.tmf.bg.ac.rs/handle/123456789/5886
AB  - Numerous structurally different amides and imides including succinimide derivatives exhibit diverse bioactive potential. The development of new compounds requires rationalization in the design in or- der to provide structural changes that guarantee favorable physico-chemical properties, pharmacological activity and safety. In the present research, a comprehensive study with comparison of the chromato- graphic lipophilicity and other physico-chemical properties of five groups of 1-arylsuccinimide derivatives was conducted. The chemometric analysis of their physico-chemical properties was carried out by us- ing unsupervised (hierarchical cluster analysis and principal component analysis) and supervised pattern recognition methods (linear discriminant analysis), while the correlations between the in silico molecular features and chromatographic lipophilicity were examined applying linear and non-linear Quantitative Structure–Retention Relationship (QSRR) approaches. The main aim of the conducted research was to determine similarities and dissimilarities among the studied 1-arylsuccinimides, to point out the molec- ular features which have significant influence on their lipophilicity, as well as to establish high-quality QSRR models which can be used in prediction of chromatographic lipophilicity of structurally similar 1-arylsuccinimides. This study is a continuation of analysis and determination of the physico-chemical properties of 1-arylsuccinimides which could be important guidelines in further in vitro and eventually in vivo studies of their biological potential.
PB  - Elsevier B.V.
T2  - Journal of Chromatography A
T1  - Comparative chemometric and quantitative structure-retention relationship analysis of anisotropic lipophilicity of 1-arylsuccinimide derivatives determined in high-performance thin-layer chromatography system with aprotic solvents
VL  - 1628
DO  - 10.1016/j.chroma.2020.461439
ER  - 

@article{
author = "Kovačević, Strahinja and Karadžić Banjac, Milica and Milošević, Nataša and Ćurčić, Jelena and Marjanović, Dunja and Todorović, Nemanja and Krmar, Jovana and Podunavac-Kuzmanović, Sanja and Banjac, Nebojša and Ušćumlić, Gordana",
year = "2020",
abstract = "Numerous structurally different amides and imides including succinimide derivatives exhibit diverse bioactive potential. The development of new compounds requires rationalization in the design in or- der to provide structural changes that guarantee favorable physico-chemical properties, pharmacological activity and safety. In the present research, a comprehensive study with comparison of the chromato- graphic lipophilicity and other physico-chemical properties of five groups of 1-arylsuccinimide derivatives was conducted. The chemometric analysis of their physico-chemical properties was carried out by us- ing unsupervised (hierarchical cluster analysis and principal component analysis) and supervised pattern recognition methods (linear discriminant analysis), while the correlations between the in silico molecular features and chromatographic lipophilicity were examined applying linear and non-linear Quantitative Structure–Retention Relationship (QSRR) approaches. The main aim of the conducted research was to determine similarities and dissimilarities among the studied 1-arylsuccinimides, to point out the molec- ular features which have significant influence on their lipophilicity, as well as to establish high-quality QSRR models which can be used in prediction of chromatographic lipophilicity of structurally similar 1-arylsuccinimides. This study is a continuation of analysis and determination of the physico-chemical properties of 1-arylsuccinimides which could be important guidelines in further in vitro and eventually in vivo studies of their biological potential.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography A",
title = "Comparative chemometric and quantitative structure-retention relationship analysis of anisotropic lipophilicity of 1-arylsuccinimide derivatives determined in high-performance thin-layer chromatography system with aprotic solvents",
volume = "1628",
doi = "10.1016/j.chroma.2020.461439"
}

Kovačević, S., Karadžić Banjac, M., Milošević, N., Ćurčić, J., Marjanović, D., Todorović, N., Krmar, J., Podunavac-Kuzmanović, S., Banjac, N.,& Ušćumlić, G.. (2020). Comparative chemometric and quantitative structure-retention relationship analysis of anisotropic lipophilicity of 1-arylsuccinimide derivatives determined in high-performance thin-layer chromatography system with aprotic solvents. in Journal of Chromatography A
Elsevier B.V.., 1628.
https://doi.org/10.1016/j.chroma.2020.461439

Kovačević S, Karadžić Banjac M, Milošević N, Ćurčić J, Marjanović D, Todorović N, Krmar J, Podunavac-Kuzmanović S, Banjac N, Ušćumlić G. Comparative chemometric and quantitative structure-retention relationship analysis of anisotropic lipophilicity of 1-arylsuccinimide derivatives determined in high-performance thin-layer chromatography system with aprotic solvents. in Journal of Chromatography A. 2020;1628.
doi:10.1016/j.chroma.2020.461439 .

Kovačević, Strahinja, Karadžić Banjac, Milica, Milošević, Nataša, Ćurčić, Jelena, Marjanović, Dunja, Todorović, Nemanja, Krmar, Jovana, Podunavac-Kuzmanović, Sanja, Banjac, Nebojša, Ušćumlić, Gordana, "Comparative chemometric and quantitative structure-retention relationship analysis of anisotropic lipophilicity of 1-arylsuccinimide derivatives determined in high-performance thin-layer chromatography system with aprotic solvents" in Journal of Chromatography A, 1628 (2020),
https://doi.org/10.1016/j.chroma.2020.461439 . .