TY  - JOUR
AU  - Tumpa, Anja
AU  - Kalinić, Marko
AU  - Jovanović, Predrag
AU  - Erić, Slavica
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
AU  - Medenica, Mirjana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2650
AB  - In this article, retention modeling of eight aminopyridines (synthesized and characterized at the Faculty of Pharmacy) in reversed-phase high performance liquid chromatography (RP-HPLC) was performed. No data related to their retention in the RP-HPLC system were found. Knowing that, it was recognized as very important to describe their retention behavior. The influences of pH of the mobile phase and the organic modifier content on the retention factors were investigated. Two theoretical models for the dependence of retention factor of organic modifier content were tested. Then, the most reliable and accurate prediction of log k was created, testing multiple linear regression model-quantitative structure-retention relationships (MLR-QSRR) and support vector regression machine-quantitative structure-retention relationships (SVM-QSRR). Initially, 400 descriptors were calculated, but four of them (POM, log D, M-SZX/RZX and m-RPCG) were included in the models. SVM-QSRR performed significantly better than the MLR model. Apart from aminopyridines, four structurally similar substances (indapamide, gliclazide, sulfamethoxazole and furosemide) were followed in the same chromatographic system. They were used as external validation set for the QSRR model (it performed well within its applicability domain, which was defined using a bounding box approach). After having described retention of eight aminopyridines with both theoretical and QSRR models, further investigations in this field can be conducted.
PB  - Oxford Univ Press Inc, Cary
T2  - Journal of Chromatographic Science
T1  - Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines
VL  - 54
IS  - 3
SP  - 436
EP  - 444
DO  - 10.1093/chromsci/bmv165
ER  - 

@article{
author = "Tumpa, Anja and Kalinić, Marko and Jovanović, Predrag and Erić, Slavica and Rakić, Tijana and Jančić-Stojanović, Biljana and Medenica, Mirjana",
year = "2016",
abstract = "In this article, retention modeling of eight aminopyridines (synthesized and characterized at the Faculty of Pharmacy) in reversed-phase high performance liquid chromatography (RP-HPLC) was performed. No data related to their retention in the RP-HPLC system were found. Knowing that, it was recognized as very important to describe their retention behavior. The influences of pH of the mobile phase and the organic modifier content on the retention factors were investigated. Two theoretical models for the dependence of retention factor of organic modifier content were tested. Then, the most reliable and accurate prediction of log k was created, testing multiple linear regression model-quantitative structure-retention relationships (MLR-QSRR) and support vector regression machine-quantitative structure-retention relationships (SVM-QSRR). Initially, 400 descriptors were calculated, but four of them (POM, log D, M-SZX/RZX and m-RPCG) were included in the models. SVM-QSRR performed significantly better than the MLR model. Apart from aminopyridines, four structurally similar substances (indapamide, gliclazide, sulfamethoxazole and furosemide) were followed in the same chromatographic system. They were used as external validation set for the QSRR model (it performed well within its applicability domain, which was defined using a bounding box approach). After having described retention of eight aminopyridines with both theoretical and QSRR models, further investigations in this field can be conducted.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journal of Chromatographic Science",
title = "Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines",
volume = "54",
number = "3",
pages = "436-444",
doi = "10.1093/chromsci/bmv165"
}

Tumpa, A., Kalinić, M., Jovanović, P., Erić, S., Rakić, T., Jančić-Stojanović, B.,& Medenica, M.. (2016). Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines. in Journal of Chromatographic Science
Oxford Univ Press Inc, Cary., 54(3), 436-444.
https://doi.org/10.1093/chromsci/bmv165

Tumpa A, Kalinić M, Jovanović P, Erić S, Rakić T, Jančić-Stojanović B, Medenica M. Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines. in Journal of Chromatographic Science. 2016;54(3):436-444.
doi:10.1093/chromsci/bmv165 .

Tumpa, Anja, Kalinić, Marko, Jovanović, Predrag, Erić, Slavica, Rakić, Tijana, Jančić-Stojanović, Biljana, Medenica, Mirjana, "Theoretical Models and QSRR in Retention Modeling of Eight Aminopyridines" in Journal of Chromatographic Science, 54, no. 3 (2016):436-444,
https://doi.org/10.1093/chromsci/bmv165 . .

TY  - JOUR
AU  - Tumpa, Anja
AU  - Miladinović, Tamara
AU  - Rakić, Tijana
AU  - Stajić, Ana
AU  - Jančić-Stojanović, Biljana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2567
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3444
AB  - A liquid chromatography method is reported for the determination of diclofenac potassium and its impurities using Quality by Design criteria. Central composite design was used for the investigation of the influence of critical parameters on performance that included the methanol concentration in the mobile phase, the pH of the aqueous phase, and the potassium dihydrogen phosphate concentration in the aqueous phase. Mathematical models enabled theoretical examination of experimental space to achieve maximal separation in minimal analysis time. A Monte Carlo simulation was used to evaluate the risk of uncertainty in model predictions, to adjusting process parameters, and to identify design space. Fractional factorial design was employed for robustness testing and method was fully validated. Optimal conditions were a C18 150mmx4.6mm, 5 mu m particle size column; a methanol -68.3mmolL(-1) potassium dihydrogenphosphate (68.7:31.3, v/v) mobile phase at pH 3.0, a flow rate of 1mL min(-1), a column temperature of 25 degrees C, and ultraviolet detection at 254nm.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Analytical Letters
T1  - Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography
VL  - 49
IS  - 4
SP  - 445
EP  - 457
DO  - 10.1080/00032719.2015.1075131
ER  - 

@article{
author = "Tumpa, Anja and Miladinović, Tamara and Rakić, Tijana and Stajić, Ana and Jančić-Stojanović, Biljana",
year = "2016",
abstract = "A liquid chromatography method is reported for the determination of diclofenac potassium and its impurities using Quality by Design criteria. Central composite design was used for the investigation of the influence of critical parameters on performance that included the methanol concentration in the mobile phase, the pH of the aqueous phase, and the potassium dihydrogen phosphate concentration in the aqueous phase. Mathematical models enabled theoretical examination of experimental space to achieve maximal separation in minimal analysis time. A Monte Carlo simulation was used to evaluate the risk of uncertainty in model predictions, to adjusting process parameters, and to identify design space. Fractional factorial design was employed for robustness testing and method was fully validated. Optimal conditions were a C18 150mmx4.6mm, 5 mu m particle size column; a methanol -68.3mmolL(-1) potassium dihydrogenphosphate (68.7:31.3, v/v) mobile phase at pH 3.0, a flow rate of 1mL min(-1), a column temperature of 25 degrees C, and ultraviolet detection at 254nm.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Analytical Letters",
title = "Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography",
volume = "49",
number = "4",
pages = "445-457",
doi = "10.1080/00032719.2015.1075131"
}

Tumpa, A., Miladinović, T., Rakić, T., Stajić, A.,& Jančić-Stojanović, B.. (2016). Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography. in Analytical Letters
Taylor & Francis Inc, Philadelphia., 49(4), 445-457.
https://doi.org/10.1080/00032719.2015.1075131

Tumpa A, Miladinović T, Rakić T, Stajić A, Jančić-Stojanović B. Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography. in Analytical Letters. 2016;49(4):445-457.
doi:10.1080/00032719.2015.1075131 .

Tumpa, Anja, Miladinović, Tamara, Rakić, Tijana, Stajić, Ana, Jančić-Stojanović, Biljana, "Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography" in Analytical Letters, 49, no. 4 (2016):445-457,
https://doi.org/10.1080/00032719.2015.1075131 . .

TY  - JOUR
AU  - Maksić, Jelena
AU  - Tumpa, Anja
AU  - Stajić, Ana
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2604
AB  - In this paper separation of granisetron and its two related substances in HILIC mode is presented. Separation was done on silica column derivatized with sulfoalkylbetaine groups (ZIC-HILIC). Firstly, retention mechanisms were assessed whereby retention factors of substances were followed in wide range of acetonitrile content (80-97%), at constant concentration of aqueous buffer (10 mM) as well as at constant pH value of 3.0. Further, in order to developed optimal HILIC method, Design of Experiments (DoE) methodology was applied. For optimization full factorial design 32 was employed. Influence of acetonitrile content and ammonium acetate concentration were investigated while pH of the water phase was kept at 3.3. Adequacy of obtained mathematical models was confirmed by ANOVA. Optimization goals (alpha > 1.15 and minimal run time) were accomplished with 94.7% of acetonitrile in mobile phase and 70 mM of ammonium acetate in water phase. Optimal point was in the middle of defined Design Space. In the next phase, robustness was experimetally tested by Rechtschaffen design. The investigated factors and their levels were: acetonitrile content (+/- 1%), ammonium acetate molarity in water phase (+/- 2 mM), pH value of water phase (+/- 0.2) and column temperature (+/- 4 degrees C). The validation scope included selectivity, linearity, accuracy and precision as well as determination of limit of detection (LOD) and limit of quantification (LOQ) for the related substances. Additionally, the validation acceptance criteria were met in all cases. Finally, the proposed method could be successfully utilized for estimation of granisetron HCl and its related substances in tablets and parenteral dosage forms, as well as for monitoring degradation under various stress conditions.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development
VL  - 123
SP  - 93
EP  - 103
DO  - 10.1016/j.jpba.2016.02.010
ER  - 

@article{
author = "Maksić, Jelena and Tumpa, Anja and Stajić, Ana and Jovanović, Marko and Rakić, Tijana and Jančić-Stojanović, Biljana",
year = "2016",
abstract = "In this paper separation of granisetron and its two related substances in HILIC mode is presented. Separation was done on silica column derivatized with sulfoalkylbetaine groups (ZIC-HILIC). Firstly, retention mechanisms were assessed whereby retention factors of substances were followed in wide range of acetonitrile content (80-97%), at constant concentration of aqueous buffer (10 mM) as well as at constant pH value of 3.0. Further, in order to developed optimal HILIC method, Design of Experiments (DoE) methodology was applied. For optimization full factorial design 32 was employed. Influence of acetonitrile content and ammonium acetate concentration were investigated while pH of the water phase was kept at 3.3. Adequacy of obtained mathematical models was confirmed by ANOVA. Optimization goals (alpha > 1.15 and minimal run time) were accomplished with 94.7% of acetonitrile in mobile phase and 70 mM of ammonium acetate in water phase. Optimal point was in the middle of defined Design Space. In the next phase, robustness was experimetally tested by Rechtschaffen design. The investigated factors and their levels were: acetonitrile content (+/- 1%), ammonium acetate molarity in water phase (+/- 2 mM), pH value of water phase (+/- 0.2) and column temperature (+/- 4 degrees C). The validation scope included selectivity, linearity, accuracy and precision as well as determination of limit of detection (LOD) and limit of quantification (LOQ) for the related substances. Additionally, the validation acceptance criteria were met in all cases. Finally, the proposed method could be successfully utilized for estimation of granisetron HCl and its related substances in tablets and parenteral dosage forms, as well as for monitoring degradation under various stress conditions.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development",
volume = "123",
pages = "93-103",
doi = "10.1016/j.jpba.2016.02.010"
}

Maksić, J., Tumpa, A., Stajić, A., Jovanović, M., Rakić, T.,& Jančić-Stojanović, B.. (2016). Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 123, 93-103.
https://doi.org/10.1016/j.jpba.2016.02.010

Maksić J, Tumpa A, Stajić A, Jovanović M, Rakić T, Jančić-Stojanović B. Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development. in Journal of Pharmaceutical and Biomedical Analysis. 2016;123:93-103.
doi:10.1016/j.jpba.2016.02.010 .

Maksić, Jelena, Tumpa, Anja, Stajić, Ana, Jovanović, Marko, Rakić, Tijana, Jančić-Stojanović, Biljana, "Hydrophilic interaction liquid chromatography in analysis of granisetron HCl and its related substances. Retention mechanisms and method development" in Journal of Pharmaceutical and Biomedical Analysis, 123 (2016):93-103,
https://doi.org/10.1016/j.jpba.2016.02.010 . .

TY  - JOUR
AU  - Tumpa, Anja
AU  - Miladinović, Tamara
AU  - Rakić, Tijana
AU  - Stajić, Ana
AU  - Jančić-Stojanović, Biljana
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2567
AB  - A liquid chromatography method is reported for the determination of diclofenac potassium and its impurities using Quality by Design criteria. Central composite design was used for the investigation of the influence of critical parameters on performance that included the methanol concentration in the mobile phase, the pH of the aqueous phase, and the potassium dihydrogen phosphate concentration in the aqueous phase. Mathematical models enabled theoretical examination of experimental space to achieve maximal separation in minimal analysis time. A Monte Carlo simulation was used to evaluate the risk of uncertainty in model predictions, to adjusting process parameters, and to identify design space. Fractional factorial design was employed for robustness testing and method was fully validated. Optimal conditions were a C18 150mmx4.6mm, 5 mu m particle size column; a methanol -68.3mmolL(-1) potassium dihydrogenphosphate (68.7:31.3, v/v) mobile phase at pH 3.0, a flow rate of 1mL min(-1), a column temperature of 25 degrees C, and ultraviolet detection at 254nm.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Analytical Letters
T1  - Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography
VL  - 49
IS  - 4
SP  - 445
EP  - 457
DO  - 10.1080/00032719.2015.1075131
ER  - 

@article{
author = "Tumpa, Anja and Miladinović, Tamara and Rakić, Tijana and Stajić, Ana and Jančić-Stojanović, Biljana",
year = "2016",
abstract = "A liquid chromatography method is reported for the determination of diclofenac potassium and its impurities using Quality by Design criteria. Central composite design was used for the investigation of the influence of critical parameters on performance that included the methanol concentration in the mobile phase, the pH of the aqueous phase, and the potassium dihydrogen phosphate concentration in the aqueous phase. Mathematical models enabled theoretical examination of experimental space to achieve maximal separation in minimal analysis time. A Monte Carlo simulation was used to evaluate the risk of uncertainty in model predictions, to adjusting process parameters, and to identify design space. Fractional factorial design was employed for robustness testing and method was fully validated. Optimal conditions were a C18 150mmx4.6mm, 5 mu m particle size column; a methanol -68.3mmolL(-1) potassium dihydrogenphosphate (68.7:31.3, v/v) mobile phase at pH 3.0, a flow rate of 1mL min(-1), a column temperature of 25 degrees C, and ultraviolet detection at 254nm.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Analytical Letters",
title = "Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography",
volume = "49",
number = "4",
pages = "445-457",
doi = "10.1080/00032719.2015.1075131"
}

Tumpa, A., Miladinović, T., Rakić, T., Stajić, A.,& Jančić-Stojanović, B.. (2016). Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography. in Analytical Letters
Taylor & Francis Inc, Philadelphia., 49(4), 445-457.
https://doi.org/10.1080/00032719.2015.1075131

Tumpa A, Miladinović T, Rakić T, Stajić A, Jančić-Stojanović B. Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography. in Analytical Letters. 2016;49(4):445-457.
doi:10.1080/00032719.2015.1075131 .

Tumpa, Anja, Miladinović, Tamara, Rakić, Tijana, Stajić, Ana, Jančić-Stojanović, Biljana, "Quality by Design Determination of Diclofenac Potassium and its Impurities by High-Performance Liquid Chromatography" in Analytical Letters, 49, no. 4 (2016):445-457,
https://doi.org/10.1080/00032719.2015.1075131 . .

TY  - JOUR
AU  - Vemić, Ana
AU  - Rakić, Tijana
AU  - Malenović, Anđelija
AU  - Medenica, Mirjana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2379
AB  - The aim of this paper is to present a development of liquid chromatographic method when chaotropic salts are used as mobile phase additives following the QbD principles. The effect of critical process parameters (column chemistry, salt nature and concentration, acetonitrile content and column temperature) on the critical quality attributes (retention of the first and last eluting peak and separation of the critical peak pairs) was studied applying the design of experiments-design space methodology (DoE-DS). D-optimal design is chosen in order to simultaneously examine both categorical and numerical factors in minimal number of experiments. Two ways for the achievement of quality assurance were performed and compared. Namely, the uncertainty originating from the models was assessed by Monte Carlo simulations propagating the error equal to the variance of the model residuals and propagating the error originating from the model coefficients' calculation. The baseline separation of pramipexole and its five impurities is achieved fulfilling all the required criteria while the method validation proved its reliability.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles
VL  - 102
SP  - 314
EP  - 320
DO  - 10.1016/j.jpba.2014.09.031
ER  - 

@article{
author = "Vemić, Ana and Rakić, Tijana and Malenović, Anđelija and Medenica, Mirjana",
year = "2015",
abstract = "The aim of this paper is to present a development of liquid chromatographic method when chaotropic salts are used as mobile phase additives following the QbD principles. The effect of critical process parameters (column chemistry, salt nature and concentration, acetonitrile content and column temperature) on the critical quality attributes (retention of the first and last eluting peak and separation of the critical peak pairs) was studied applying the design of experiments-design space methodology (DoE-DS). D-optimal design is chosen in order to simultaneously examine both categorical and numerical factors in minimal number of experiments. Two ways for the achievement of quality assurance were performed and compared. Namely, the uncertainty originating from the models was assessed by Monte Carlo simulations propagating the error equal to the variance of the model residuals and propagating the error originating from the model coefficients' calculation. The baseline separation of pramipexole and its five impurities is achieved fulfilling all the required criteria while the method validation proved its reliability.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles",
volume = "102",
pages = "314-320",
doi = "10.1016/j.jpba.2014.09.031"
}

Vemić, A., Rakić, T., Malenović, A.,& Medenica, M.. (2015). Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 102, 314-320.
https://doi.org/10.1016/j.jpba.2014.09.031

Vemić A, Rakić T, Malenović A, Medenica M. Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles. in Journal of Pharmaceutical and Biomedical Analysis. 2015;102:314-320.
doi:10.1016/j.jpba.2014.09.031 .

Vemić, Ana, Rakić, Tijana, Malenović, Anđelija, Medenica, Mirjana, "Chaotropic salts in liquid chromatographic method development for the determination of pramipexole and its impurities following quality-by-design principles" in Journal of Pharmaceutical and Biomedical Analysis, 102 (2015):314-320,
https://doi.org/10.1016/j.jpba.2014.09.031 . .

TY  - JOUR
AU  - Tumpa, Anja
AU  - Rakić, Tijana
AU  - Jovanović, Marko
AU  - Jančić-Stojanović, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2332
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3443
AB  - The retention behavior of substances in hydrophilic interaction liquid chromatography (HILIC) is difficult to predict. Mixture investigated in this paper consists of acetylsalicylic acid, amlodipine, impurity A of amlodipine, and atenolol, a very often used combination in treatment of some cardiovascular diseases. Retention behavior dependence on the most influential chromatographic factors is described by mathematical models, with the special emphasis on pH of the mobile phase. D-optimal design is applied to generate more complex models and to obtain more accurate results. Comparison of Predicted R-2 values of quadratic and cubic model for pH dependence (0.847 and 0.934, respectively) shows that the cubic model has significantly better prediction ability than quadratic in the investigated system. After describing retention behavior, chemometrical tools (indirect modeling of complex chromatographic responses and grid point search optimization) are used to locate the optimal conditions for analyzed mixture in terms of satisfactory separation and minimal analysis duration. The optimal conditions are Column: Kinetex HILIC 100 A (100mmx4.5mm, 2.6 mu m particle size); injection volume: 5 mu L; flow rate: 1mLmin(-1); column temperature: 30 degrees C; detection wavelength: 254nm; mobile phase: acetonitrile-water phase (75mM ammonium acetate, pH 5.3) (91:9V/V).
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology
VL  - 38
IS  - 16
SP  - 1555
EP  - 1560
DO  - 10.1080/10826076.2015.1077863
ER  - 

@article{
author = "Tumpa, Anja and Rakić, Tijana and Jovanović, Marko and Jančić-Stojanović, Biljana",
year = "2015",
abstract = "The retention behavior of substances in hydrophilic interaction liquid chromatography (HILIC) is difficult to predict. Mixture investigated in this paper consists of acetylsalicylic acid, amlodipine, impurity A of amlodipine, and atenolol, a very often used combination in treatment of some cardiovascular diseases. Retention behavior dependence on the most influential chromatographic factors is described by mathematical models, with the special emphasis on pH of the mobile phase. D-optimal design is applied to generate more complex models and to obtain more accurate results. Comparison of Predicted R-2 values of quadratic and cubic model for pH dependence (0.847 and 0.934, respectively) shows that the cubic model has significantly better prediction ability than quadratic in the investigated system. After describing retention behavior, chemometrical tools (indirect modeling of complex chromatographic responses and grid point search optimization) are used to locate the optimal conditions for analyzed mixture in terms of satisfactory separation and minimal analysis duration. The optimal conditions are Column: Kinetex HILIC 100 A (100mmx4.5mm, 2.6 mu m particle size); injection volume: 5 mu L; flow rate: 1mLmin(-1); column temperature: 30 degrees C; detection wavelength: 254nm; mobile phase: acetonitrile-water phase (75mM ammonium acetate, pH 5.3) (91:9V/V).",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology",
volume = "38",
number = "16",
pages = "1555-1560",
doi = "10.1080/10826076.2015.1077863"
}

Tumpa, A., Rakić, T., Jovanović, M.,& Jančić-Stojanović, B.. (2015). Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 38(16), 1555-1560.
https://doi.org/10.1080/10826076.2015.1077863

Tumpa A, Rakić T, Jovanović M, Jančić-Stojanović B. Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology. in Journal of Liquid Chromatography & Related Technologies. 2015;38(16):1555-1560.
doi:10.1080/10826076.2015.1077863 .

Tumpa, Anja, Rakić, Tijana, Jovanović, Marko, Jančić-Stojanović, Biljana, "Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology" in Journal of Liquid Chromatography & Related Technologies, 38, no. 16 (2015):1555-1560,
https://doi.org/10.1080/10826076.2015.1077863 . .

TY  - JOUR
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Tumpa, Anja
AU  - Jančić-Stojanović, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3418
AB  - This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm x 4.6 mm, 5 mu m particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 degrees C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities
VL  - 110
SP  - 42
EP  - 48
DO  - 10.1016/j.jpba.2015.02.046
ER  - 

@article{
author = "Jovanović, Marko and Rakić, Tijana and Tumpa, Anja and Jančić-Stojanović, Biljana",
year = "2015",
abstract = "This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm x 4.6 mm, 5 mu m particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 degrees C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities",
volume = "110",
pages = "42-48",
doi = "10.1016/j.jpba.2015.02.046"
}

Jovanović, M., Rakić, T., Tumpa, A.,& Jančić-Stojanović, B.. (2015). Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 110, 42-48.
https://doi.org/10.1016/j.jpba.2015.02.046

Jovanović M, Rakić T, Tumpa A, Jančić-Stojanović B. Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities. in Journal of Pharmaceutical and Biomedical Analysis. 2015;110:42-48.
doi:10.1016/j.jpba.2015.02.046 .

Jovanović, Marko, Rakić, Tijana, Tumpa, Anja, Jančić-Stojanović, Biljana, "Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities" in Journal of Pharmaceutical and Biomedical Analysis, 110 (2015):42-48,
https://doi.org/10.1016/j.jpba.2015.02.046 . .

TY  - JOUR
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Ivanović, Darko
AU  - Jančić-Stojanović, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2400
AB  - Hydrophilic interaction liquid chromatography (HILIC) has emerged as an alternative separation technique for small polar compounds. Design of Experiments (DoE) methodology in the analysis of the retention behavior and method development have been shown to be successful. This article addresses the retention behavior and optimization of chromatographic separation of a model mixture consisting of four sympathomimetic drugs (ephedrine, pseudoephedrine, phenylephrine, synephrine), on a bare silica column by HILIC. The acetonitrile content, pH of the aqueous phase, and concentration of ammonium acetate in aqueous phase were optimized according to the matrix of Box-Behnken design, and retention data were fitted to second-order polynomial models. The obtained coefficients of determination R-2 were higher than 0.990 and adjusted R-2 exceeded 0.972, while the lowest value for Predicted R-2 was 0.845. Beside of statistical analysis, graphical estimation of retention behavior was performed. In order to optimize the separation, indirect modeling of selectivity factors of critical peak pairs (the diastereoisomers ephedrine/pseudoephedrine and the positional isomers phenylephrine/synephrine) and grid point search approach were employed. After the development of the grids, optimal chromatographic conditions were selected (acetonitrile content 91%, pH of the aqueous phase 4.5 and ammonium acetate concetration 35mmolL(-1)), providing a total analysis time of 14min.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Instrumentation Science & Technology
T1  - Optimization of the Separation of Ephedrine, Pseudoephedrine, Phenylephrine, and Synephrine by Hydrophilic Interaction Liquid Chromatography Employing Experimental Design Methodology
VL  - 43
IS  - 2
SP  - 156
EP  - 169
DO  - 10.1080/10739149.2014.910670
ER  - 

@article{
author = "Jovanović, Marko and Rakić, Tijana and Ivanović, Darko and Jančić-Stojanović, Biljana",
year = "2015",
abstract = "Hydrophilic interaction liquid chromatography (HILIC) has emerged as an alternative separation technique for small polar compounds. Design of Experiments (DoE) methodology in the analysis of the retention behavior and method development have been shown to be successful. This article addresses the retention behavior and optimization of chromatographic separation of a model mixture consisting of four sympathomimetic drugs (ephedrine, pseudoephedrine, phenylephrine, synephrine), on a bare silica column by HILIC. The acetonitrile content, pH of the aqueous phase, and concentration of ammonium acetate in aqueous phase were optimized according to the matrix of Box-Behnken design, and retention data were fitted to second-order polynomial models. The obtained coefficients of determination R-2 were higher than 0.990 and adjusted R-2 exceeded 0.972, while the lowest value for Predicted R-2 was 0.845. Beside of statistical analysis, graphical estimation of retention behavior was performed. In order to optimize the separation, indirect modeling of selectivity factors of critical peak pairs (the diastereoisomers ephedrine/pseudoephedrine and the positional isomers phenylephrine/synephrine) and grid point search approach were employed. After the development of the grids, optimal chromatographic conditions were selected (acetonitrile content 91%, pH of the aqueous phase 4.5 and ammonium acetate concetration 35mmolL(-1)), providing a total analysis time of 14min.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Instrumentation Science & Technology",
title = "Optimization of the Separation of Ephedrine, Pseudoephedrine, Phenylephrine, and Synephrine by Hydrophilic Interaction Liquid Chromatography Employing Experimental Design Methodology",
volume = "43",
number = "2",
pages = "156-169",
doi = "10.1080/10739149.2014.910670"
}

Jovanović, M., Rakić, T., Ivanović, D.,& Jančić-Stojanović, B.. (2015). Optimization of the Separation of Ephedrine, Pseudoephedrine, Phenylephrine, and Synephrine by Hydrophilic Interaction Liquid Chromatography Employing Experimental Design Methodology. in Instrumentation Science & Technology
Taylor & Francis Inc, Philadelphia., 43(2), 156-169.
https://doi.org/10.1080/10739149.2014.910670

Jovanović M, Rakić T, Ivanović D, Jančić-Stojanović B. Optimization of the Separation of Ephedrine, Pseudoephedrine, Phenylephrine, and Synephrine by Hydrophilic Interaction Liquid Chromatography Employing Experimental Design Methodology. in Instrumentation Science & Technology. 2015;43(2):156-169.
doi:10.1080/10739149.2014.910670 .

Jovanović, Marko, Rakić, Tijana, Ivanović, Darko, Jančić-Stojanović, Biljana, "Optimization of the Separation of Ephedrine, Pseudoephedrine, Phenylephrine, and Synephrine by Hydrophilic Interaction Liquid Chromatography Employing Experimental Design Methodology" in Instrumentation Science & Technology, 43, no. 2 (2015):156-169,
https://doi.org/10.1080/10739149.2014.910670 . .

TY  - JOUR
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Tumpa, Anja
AU  - Jančić-Stojanović, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2398
AB  - This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm x 4.6 mm, 5 mu m particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 degrees C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities
VL  - 110
SP  - 42
EP  - 48
DO  - 10.1016/j.jpba.2015.02.046
ER  - 

@article{
author = "Jovanović, Marko and Rakić, Tijana and Tumpa, Anja and Jančić-Stojanović, Biljana",
year = "2015",
abstract = "This study presents the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol, its endo-isomer and three impurities following Quality by Design (QbD) approach. The main objective of the method was to identify the conditions where adequate separation quality in minimal analysis duration could be achieved within a robust region that guarantees the stability of method performance. The relationship between critical process parameters (acetonitrile content in the mobile phase, pH of the water phase and ammonium acetate concentration in the water phase) and critical quality attributes is created applying design of experiments methodology. The defined mathematical models and Monte Carlo simulation are used to evaluate the risk of uncertainty in models prediction and incertitude in adjusting the process parameters and to identify the design space. The borders of the design space are experimentally verified and confirmed that the quality of the method is preserved in this region. Moreover, Plackett-Burman design is applied for experimental robustness testing and method is fully validated to verify the adequacy of selected optimal conditions: the analytical column ZIC HILIC (100 mm x 4.6 mm, 5 mu m particle size); mobile phase consisted of acetonitrile-water phase (72 mM ammonium acetate, pH adjusted to 6.5 with glacial acetic acid) (86.7:13.3) v/v; column temperature 25 degrees C, mobile phase flow rate 1 mL min(-1), wavelength of detection 254 nm.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities",
volume = "110",
pages = "42-48",
doi = "10.1016/j.jpba.2015.02.046"
}

Jovanović, M., Rakić, T., Tumpa, A.,& Jančić-Stojanović, B.. (2015). Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 110, 42-48.
https://doi.org/10.1016/j.jpba.2015.02.046

Jovanović M, Rakić T, Tumpa A, Jančić-Stojanović B. Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities. in Journal of Pharmaceutical and Biomedical Analysis. 2015;110:42-48.
doi:10.1016/j.jpba.2015.02.046 .

Jovanović, Marko, Rakić, Tijana, Tumpa, Anja, Jančić-Stojanović, Biljana, "Quality by Design approach in the development of hydrophilic interaction liquid chromatographic method for the analysis of iohexol and its impurities" in Journal of Pharmaceutical and Biomedical Analysis, 110 (2015):42-48,
https://doi.org/10.1016/j.jpba.2015.02.046 . .

TY  - JOUR
AU  - Kasagić-Vujanović, Irena
AU  - Jančić-Stojanović, Biljana
AU  - Rakić, Tijana
AU  - Ivanović, Darko
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2392
AB  - In this paper chemometrically-assisted optimization and validation of hydrophilic interaction liquid chromatographic (HILIC) method for the quantitative analysis of amlodipine besylate (AB) and bisoprolol fumarate (BF) in pharmaceuticals are presented. In this study, the development of HILIC method for AB and BF separation was performed by a systematic approach which included Design of Experiments (DoE) methodology. First, in method optimization, a central composite design was applied. Influence of the acetonitrile content in the mobile phase, pH of the aqueous phase, and concentration of ammonium acetate on selected chromatographic responses was investigated. Optimal chromatographic conditions in terms of adequate separation and minimal analysis duration were set by graphical optimization overlapping the contour plots as: acetonitrile-water phase (10mM ammonium acetate, pH 4.0 adjusted with glacial acetic acid) (92:8, v/v), column Luna HILIC 200 A, 150mmx4.6mm, 5 mu m particle size, column temperature 30 degrees C, flow rate 1mL min(-1), and UV detection at 230nm. After this step, method robustness was tested using a 2(5-1) fractional factorial design. Statistical and graphical evaluation of results confirmed robustness of the method and then the method was fully validated. Finally, the proposed method was successfully applied for AB and BF determination in pharmaceuticals.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Design of Experiments in Optimization and Validation of a Hydrophilic Interaction Liquid Chromatography Method for Determination of Amlodipine Besylate and Bisoprolol Fumarate
VL  - 38
IS  - 8
SP  - 919
EP  - 928
DO  - 10.1080/10826076.2014.991872
ER  - 

@article{
author = "Kasagić-Vujanović, Irena and Jančić-Stojanović, Biljana and Rakić, Tijana and Ivanović, Darko",
year = "2015",
abstract = "In this paper chemometrically-assisted optimization and validation of hydrophilic interaction liquid chromatographic (HILIC) method for the quantitative analysis of amlodipine besylate (AB) and bisoprolol fumarate (BF) in pharmaceuticals are presented. In this study, the development of HILIC method for AB and BF separation was performed by a systematic approach which included Design of Experiments (DoE) methodology. First, in method optimization, a central composite design was applied. Influence of the acetonitrile content in the mobile phase, pH of the aqueous phase, and concentration of ammonium acetate on selected chromatographic responses was investigated. Optimal chromatographic conditions in terms of adequate separation and minimal analysis duration were set by graphical optimization overlapping the contour plots as: acetonitrile-water phase (10mM ammonium acetate, pH 4.0 adjusted with glacial acetic acid) (92:8, v/v), column Luna HILIC 200 A, 150mmx4.6mm, 5 mu m particle size, column temperature 30 degrees C, flow rate 1mL min(-1), and UV detection at 230nm. After this step, method robustness was tested using a 2(5-1) fractional factorial design. Statistical and graphical evaluation of results confirmed robustness of the method and then the method was fully validated. Finally, the proposed method was successfully applied for AB and BF determination in pharmaceuticals.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Design of Experiments in Optimization and Validation of a Hydrophilic Interaction Liquid Chromatography Method for Determination of Amlodipine Besylate and Bisoprolol Fumarate",
volume = "38",
number = "8",
pages = "919-928",
doi = "10.1080/10826076.2014.991872"
}

Kasagić-Vujanović, I., Jančić-Stojanović, B., Rakić, T.,& Ivanović, D.. (2015). Design of Experiments in Optimization and Validation of a Hydrophilic Interaction Liquid Chromatography Method for Determination of Amlodipine Besylate and Bisoprolol Fumarate. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 38(8), 919-928.
https://doi.org/10.1080/10826076.2014.991872

Kasagić-Vujanović I, Jančić-Stojanović B, Rakić T, Ivanović D. Design of Experiments in Optimization and Validation of a Hydrophilic Interaction Liquid Chromatography Method for Determination of Amlodipine Besylate and Bisoprolol Fumarate. in Journal of Liquid Chromatography & Related Technologies. 2015;38(8):919-928.
doi:10.1080/10826076.2014.991872 .

Kasagić-Vujanović, Irena, Jančić-Stojanović, Biljana, Rakić, Tijana, Ivanović, Darko, "Design of Experiments in Optimization and Validation of a Hydrophilic Interaction Liquid Chromatography Method for Determination of Amlodipine Besylate and Bisoprolol Fumarate" in Journal of Liquid Chromatography & Related Technologies, 38, no. 8 (2015):919-928,
https://doi.org/10.1080/10826076.2014.991872 . .

TY  - JOUR
AU  - Tumpa, Anja
AU  - Rakić, Tijana
AU  - Jovanović, Marko
AU  - Jančić-Stojanović, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2332
AB  - The retention behavior of substances in hydrophilic interaction liquid chromatography (HILIC) is difficult to predict. Mixture investigated in this paper consists of acetylsalicylic acid, amlodipine, impurity A of amlodipine, and atenolol, a very often used combination in treatment of some cardiovascular diseases. Retention behavior dependence on the most influential chromatographic factors is described by mathematical models, with the special emphasis on pH of the mobile phase. D-optimal design is applied to generate more complex models and to obtain more accurate results. Comparison of Predicted R-2 values of quadratic and cubic model for pH dependence (0.847 and 0.934, respectively) shows that the cubic model has significantly better prediction ability than quadratic in the investigated system. After describing retention behavior, chemometrical tools (indirect modeling of complex chromatographic responses and grid point search optimization) are used to locate the optimal conditions for analyzed mixture in terms of satisfactory separation and minimal analysis duration. The optimal conditions are Column: Kinetex HILIC 100 A (100mmx4.5mm, 2.6 mu m particle size); injection volume: 5 mu L; flow rate: 1mLmin(-1); column temperature: 30 degrees C; detection wavelength: 254nm; mobile phase: acetonitrile-water phase (75mM ammonium acetate, pH 5.3) (91:9V/V).
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology
VL  - 38
IS  - 16
SP  - 1555
EP  - 1560
DO  - 10.1080/10826076.2015.1077863
ER  - 

@article{
author = "Tumpa, Anja and Rakić, Tijana and Jovanović, Marko and Jančić-Stojanović, Biljana",
year = "2015",
abstract = "The retention behavior of substances in hydrophilic interaction liquid chromatography (HILIC) is difficult to predict. Mixture investigated in this paper consists of acetylsalicylic acid, amlodipine, impurity A of amlodipine, and atenolol, a very often used combination in treatment of some cardiovascular diseases. Retention behavior dependence on the most influential chromatographic factors is described by mathematical models, with the special emphasis on pH of the mobile phase. D-optimal design is applied to generate more complex models and to obtain more accurate results. Comparison of Predicted R-2 values of quadratic and cubic model for pH dependence (0.847 and 0.934, respectively) shows that the cubic model has significantly better prediction ability than quadratic in the investigated system. After describing retention behavior, chemometrical tools (indirect modeling of complex chromatographic responses and grid point search optimization) are used to locate the optimal conditions for analyzed mixture in terms of satisfactory separation and minimal analysis duration. The optimal conditions are Column: Kinetex HILIC 100 A (100mmx4.5mm, 2.6 mu m particle size); injection volume: 5 mu L; flow rate: 1mLmin(-1); column temperature: 30 degrees C; detection wavelength: 254nm; mobile phase: acetonitrile-water phase (75mM ammonium acetate, pH 5.3) (91:9V/V).",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology",
volume = "38",
number = "16",
pages = "1555-1560",
doi = "10.1080/10826076.2015.1077863"
}

Tumpa, A., Rakić, T., Jovanović, M.,& Jančić-Stojanović, B.. (2015). Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 38(16), 1555-1560.
https://doi.org/10.1080/10826076.2015.1077863

Tumpa A, Rakić T, Jovanović M, Jančić-Stojanović B. Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology. in Journal of Liquid Chromatography & Related Technologies. 2015;38(16):1555-1560.
doi:10.1080/10826076.2015.1077863 .

Tumpa, Anja, Rakić, Tijana, Jovanović, Marko, Jančić-Stojanović, Biljana, "Optimization of Chromatographic Separation of Acetylsalicylic Acid, Amlodipine, Impurity a of Amlodipine, and Atenolol in Hydrophilic Interaction Liquid Chromatography Employing DoE Methodology" in Journal of Liquid Chromatography & Related Technologies, 38, no. 16 (2015):1555-1560,
https://doi.org/10.1080/10826076.2015.1077863 . .

TY  - JOUR
AU  - Maksić, Jelena
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Popović, Igor
AU  - Ivanović, Darko
AU  - Jančić-Stojanović, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2318
AB  - In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box-Behnken design was utilized, and on the basis of the obtained models factor effects were examined. Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions. Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed.
PB  - Oxford Univ Press Inc, Cary
T2  - Journal of Chromatographic Science
T1  - Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography
VL  - 53
IS  - 5
SP  - 680
EP  - 686
DO  - 10.1093/chromsci/bmu102
ER  - 

@article{
author = "Maksić, Jelena and Jovanović, Marko and Rakić, Tijana and Popović, Igor and Ivanović, Darko and Jančić-Stojanović, Biljana",
year = "2015",
abstract = "In this paper, chromatographic analysis of active substance olopatadine hydrochloride, which is used in eye drops as antihistaminic agent, and its impurity E isomer by hydrophilic interaction liquid chromatography (HILIC) and application of design of experiments (DoE) methodology are presented. In addition, benzalkonium chloride is very often used as a preservative in eye drops. Therefore, the evaluation of its chromatographic behavior in HILIC was carried out as well. In order to estimate chromatographic behavior and set optimal chromatographic conditions, DoE methodology was applied. After the selection of important chromatographic factors, Box-Behnken design was utilized, and on the basis of the obtained models factor effects were examined. Then, multi-objective robust optimization is performed aiming to obtain chromatographic conditions that comply with several quality criteria simultaneously: adequate and robust separation of critical peak pair and maximum retention of the first eluting peak. The optimal conditions are identified by using grid point search methodology. The experimental verification confirmed the adequacy of the defined optimal conditions. Finally, under optimal chromatographic conditions, the method was validated and applicability of the proposed method was confirmed.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journal of Chromatographic Science",
title = "Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography",
volume = "53",
number = "5",
pages = "680-686",
doi = "10.1093/chromsci/bmu102"
}

Maksić, J., Jovanović, M., Rakić, T., Popović, I., Ivanović, D.,& Jančić-Stojanović, B.. (2015). Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography. in Journal of Chromatographic Science
Oxford Univ Press Inc, Cary., 53(5), 680-686.
https://doi.org/10.1093/chromsci/bmu102

Maksić J, Jovanović M, Rakić T, Popović I, Ivanović D, Jančić-Stojanović B. Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography. in Journal of Chromatographic Science. 2015;53(5):680-686.
doi:10.1093/chromsci/bmu102 .

Maksić, Jelena, Jovanović, Marko, Rakić, Tijana, Popović, Igor, Ivanović, Darko, Jančić-Stojanović, Biljana, "Chromatographic Analysis of Olopatadine in Hydrophilic Interaction Liquid Chromatography" in Journal of Chromatographic Science, 53, no. 5 (2015):680-686,
https://doi.org/10.1093/chromsci/bmu102 . .

TY  - JOUR
AU  - Vemić, Ana
AU  - Malenović, Anđelija
AU  - Rakić, Tijana
AU  - Kostić, Nada
AU  - Jančić-Stojanović, Biljana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2079
AB  - Certain chemometrical tools allow an efficient way to provide valuable data to evaluate the retention behavior of analytes in liquid chromatography. In this study of the retention behavior of azole antifungals, the experimental design was applied in combination with artificial neural networks (ANNs). Three potentially significant factors (methanol content, pH of the mobile phase and column temperature) were incorporated in the plan of experiments, defined by central composite design. As the system outputs, the retention factors of all six investigated substances (fluconazole, ketoconazole, bifonazole, clotrimazole, econazole and miconazole) were determined. The pattern for the analyzed behavior of the system was created by employing ANNs. The final, optimized topology of the highly predictive network was 3-8-6. Twelve experiments were used in a training set, whereas a back-propagation algorithm was optimal for network training. The ability of the defined network to predict the retention of the investigated azoles was confirmed by correlations higher than 0.9912 for all analytes. The presented approach allowed the adequate prediction of the retention behavior of azoles, in addition to the extraction of important information for a better understanding of the analyzed system.
PB  - Oxford Univ Press Inc, Cary
T2  - Journal of Chromatographic Science
T1  - Chemometrical Tools in the Study of the Retention Behavior of Azole Antifungals
VL  - 52
IS  - 2
SP  - 95
EP  - 102
DO  - 10.1093/chromsci/bms211
ER  - 

@article{
author = "Vemić, Ana and Malenović, Anđelija and Rakić, Tijana and Kostić, Nada and Jančić-Stojanović, Biljana",
year = "2014",
abstract = "Certain chemometrical tools allow an efficient way to provide valuable data to evaluate the retention behavior of analytes in liquid chromatography. In this study of the retention behavior of azole antifungals, the experimental design was applied in combination with artificial neural networks (ANNs). Three potentially significant factors (methanol content, pH of the mobile phase and column temperature) were incorporated in the plan of experiments, defined by central composite design. As the system outputs, the retention factors of all six investigated substances (fluconazole, ketoconazole, bifonazole, clotrimazole, econazole and miconazole) were determined. The pattern for the analyzed behavior of the system was created by employing ANNs. The final, optimized topology of the highly predictive network was 3-8-6. Twelve experiments were used in a training set, whereas a back-propagation algorithm was optimal for network training. The ability of the defined network to predict the retention of the investigated azoles was confirmed by correlations higher than 0.9912 for all analytes. The presented approach allowed the adequate prediction of the retention behavior of azoles, in addition to the extraction of important information for a better understanding of the analyzed system.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journal of Chromatographic Science",
title = "Chemometrical Tools in the Study of the Retention Behavior of Azole Antifungals",
volume = "52",
number = "2",
pages = "95-102",
doi = "10.1093/chromsci/bms211"
}

Vemić, A., Malenović, A., Rakić, T., Kostić, N.,& Jančić-Stojanović, B.. (2014). Chemometrical Tools in the Study of the Retention Behavior of Azole Antifungals. in Journal of Chromatographic Science
Oxford Univ Press Inc, Cary., 52(2), 95-102.
https://doi.org/10.1093/chromsci/bms211

Vemić A, Malenović A, Rakić T, Kostić N, Jančić-Stojanović B. Chemometrical Tools in the Study of the Retention Behavior of Azole Antifungals. in Journal of Chromatographic Science. 2014;52(2):95-102.
doi:10.1093/chromsci/bms211 .

Vemić, Ana, Malenović, Anđelija, Rakić, Tijana, Kostić, Nada, Jančić-Stojanović, Biljana, "Chemometrical Tools in the Study of the Retention Behavior of Azole Antifungals" in Journal of Chromatographic Science, 52, no. 2 (2014):95-102,
https://doi.org/10.1093/chromsci/bms211 . .

TY  - JOUR
AU  - Kojić-Marinković, Slavica
AU  - Tumbas, Mihaela
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2279
AB  - In this paper, application of Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium valproate. As factors which could have influence on method's robustness content of acetonitrile, concentration of sodium dihydrogenphosphate, pH of the mobile phase, column's temperature, flow rate and wavelenght were investigated. In aim to create plan of experiments for Plackett-Burman design on six real factors, 5 dummies were added. In total, 11 factors were investigated throught 12 experiments. As qualitative responses retention times, number of theoretical plates and peak symmetry were followed while as quantitative response peak area was followed. On the basis of the obtained results with statistical and graphical methods, influence of investigated factors on system responses were defined. Further, for significant factors non-significant interval was defined e. g. range in which factor could be change without influence on response. Finally, results were used for determination of parameters for system suitability tests.
AB  - U ovom radu opisana je primena Plaket-Burman dizajna u proceni robusnosti metode tečne hromatografije za određivanje sadržaja natrijum-valproata. Kao faktori koji mogu uticati na robusnost metode ispitani su sadržaj acetonitrila, koncentracija natrijum-dihidrogenfosfata, pH vrednost mobilne faze, temperatura kolone, protok mobilne faze i talasna dužina detekcije. U cilju kreiranja plana eksperimenta prema Plaket-Burman dizajnu, na 6 pravih faktora dodato je 5 veštačkih faktora i tako je ispitano 11 faktora izvođenjem 12 eksperimenata. Kao odgovori sistema praćeni su retenciono vreme, broj teorijskih platoa i simetrija pika kao kvalitativni odgovori, dok je kao kvantitativni odgovor praćena površina pika. Na osnovu dobijenih rezultata, a primenom odgovarajućih statističkih i grafičkih metoda, procenjen je uticaj ispitivanih faktora na posmatrane odgovore sistema. Pored toga, za značajne faktore određen je interval pouzdanosti tj. opseg u okviru koga se mogu menjati, a da to ne utiče značajno na odgovor sistema. Na kraju, na osnovu dobijenih rezultata, određeni su i parametri za proveru pogodnosti sistema.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat
T1  - Plaket-Burman dizajn u proceni robusnosti metode tečne hromatografije za određivanje sadržaja natrijum-valproata
VL  - 64
IS  - 2
SP  - 128
EP  - 143
DO  - 10.5937/arhfarm1402128K
ER  - 

@article{
author = "Kojić-Marinković, Slavica and Tumbas, Mihaela and Rakić, Tijana and Jančić-Stojanović, Biljana",
year = "2014",
abstract = "In this paper, application of Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium valproate. As factors which could have influence on method's robustness content of acetonitrile, concentration of sodium dihydrogenphosphate, pH of the mobile phase, column's temperature, flow rate and wavelenght were investigated. In aim to create plan of experiments for Plackett-Burman design on six real factors, 5 dummies were added. In total, 11 factors were investigated throught 12 experiments. As qualitative responses retention times, number of theoretical plates and peak symmetry were followed while as quantitative response peak area was followed. On the basis of the obtained results with statistical and graphical methods, influence of investigated factors on system responses were defined. Further, for significant factors non-significant interval was defined e. g. range in which factor could be change without influence on response. Finally, results were used for determination of parameters for system suitability tests., U ovom radu opisana je primena Plaket-Burman dizajna u proceni robusnosti metode tečne hromatografije za određivanje sadržaja natrijum-valproata. Kao faktori koji mogu uticati na robusnost metode ispitani su sadržaj acetonitrila, koncentracija natrijum-dihidrogenfosfata, pH vrednost mobilne faze, temperatura kolone, protok mobilne faze i talasna dužina detekcije. U cilju kreiranja plana eksperimenta prema Plaket-Burman dizajnu, na 6 pravih faktora dodato je 5 veštačkih faktora i tako je ispitano 11 faktora izvođenjem 12 eksperimenata. Kao odgovori sistema praćeni su retenciono vreme, broj teorijskih platoa i simetrija pika kao kvalitativni odgovori, dok je kao kvantitativni odgovor praćena površina pika. Na osnovu dobijenih rezultata, a primenom odgovarajućih statističkih i grafičkih metoda, procenjen je uticaj ispitivanih faktora na posmatrane odgovore sistema. Pored toga, za značajne faktore određen je interval pouzdanosti tj. opseg u okviru koga se mogu menjati, a da to ne utiče značajno na odgovor sistema. Na kraju, na osnovu dobijenih rezultata, određeni su i parametri za proveru pogodnosti sistema.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat, Plaket-Burman dizajn u proceni robusnosti metode tečne hromatografije za određivanje sadržaja natrijum-valproata",
volume = "64",
number = "2",
pages = "128-143",
doi = "10.5937/arhfarm1402128K"
}

Kojić-Marinković, S., Tumbas, M., Rakić, T.,& Jančić-Stojanović, B.. (2014). Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 64(2), 128-143.
https://doi.org/10.5937/arhfarm1402128K

Kojić-Marinković S, Tumbas M, Rakić T, Jančić-Stojanović B. Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat. in Arhiv za farmaciju. 2014;64(2):128-143.
doi:10.5937/arhfarm1402128K .

Kojić-Marinković, Slavica, Tumbas, Mihaela, Rakić, Tijana, Jančić-Stojanović, Biljana, "Plackett-Burman design in robustness testing of liquid chromatographic method for determination of sodium-valproat" in Arhiv za farmaciju, 64, no. 2 (2014):128-143,
https://doi.org/10.5937/arhfarm1402128K . .

TY  - JOUR
AU  - Rakić, Tijana
AU  - Jovanović, Marko
AU  - Tumpa, Anja
AU  - Jančić-Stojanović, Biljana
AU  - Medenica, Mirjana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2277
AB  - This paper presents the robust optimization of hydrophilic interaction liquid chromatographic method for the analysis of bisoprolol and its impurities A and C. Chemometric strategy is applied for detailed understanding of system's behavior and establishing the mathematical relationship between investigated factors (acetonitrile content in the mobile phase, pH of the water phase and buffer concentration in the water phase) and chromatographic responses. Grid point search methodology is then performed with the aim to identify the point with satisfactory separation quality for all analyzed substances and to achieve minimal analysis duration. Oversized chromatograms are made creating an extra band broadening for each chromatographic peak corresponding to the value of standard deviation in order to evaluate the incertitude originating from the model uncertainty. On the other hand, the uncertainty originating from the variation of experimental parameters is assessed by simulated experimental design robustness testing. Finally, the obtained robust optimal conditions were: chromatographic column Kinetex HILIC 100Å (100 mm x 4.5 mm, 2.6 mm particle size); mobile phase composed of acetonitrile - water phase (35 mM ammonium acetate, pH 4.9 adjusted with glacial acetic acid) (85:15 v/v); flow rate 1 mL min-1, column temperature 30°C and UV detection at 254 nm.
AB  - U ovom radu prikazana je optimizacija metode tečne hromatografije hidrofilnih interakcija za analizu bisoprolola i njegovih nečistoća A i C uz procenu mogućnosti variranja položaja pikova. Primenjena je hemometrijska strategija za detaljno razumevanje ponašanja sistema i uspostavljanje matematičke veze između ispitivanih faktora (sadržaj acetonitrila u mobilnoj fazi, pH vrednost vodene faze i koncentracija pufera u vodenoj fazi) i hromatografskih odgovora. Enumerativna tehnika optimizacije upotrebljena je za identifikaciju tačke koja pokazuje zadovoljavajući kvalitet razdvajanja svih ispitivanih supstanci i minimalno vreme trajanja analize. Kreirani su prošireni hromatogrami širenjem pikova svih ispitivanih supstanci za vrednosti standardne devijacije kako bi se procenila mogućnost greške odgovora koja potiče iz greške matematičkog modela. Mogućnost greške koja potiče iz greške u podešavanju eksperimentalnih parametara procenjena je simuliranim testiranjem robusnosti primenom eksperimentalnog dizajna. Konačno, dobijeni optimalni uslovi bili su: hromatografska kolona Kinetex HILIC 100Å (100 mm x 4,5 mm, 2,6 mm veličina čestica); mobilna faza sastavljena od smeše acetonitril - vodena faza (35 mM amonijum-acetat, pH 4,9 podešen glacijalnom sirćetnom kiselinom) (85:15 v/v); protok 1 mL min-1, temperatura kolone 30°C i UV detekcija na 254 nm.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Optimization of HILIC method for the analysis of bisoprolol and its impurities considering uncertainties in peak position
T1  - Optimizacija HILIC metode za analizu bisoprolola i njegovih nečistoća uz procenu mogućnosti variranja položaja pikova
VL  - 64
IS  - 2
SP  - 95
EP  - 111
DO  - 10.5937/arhfarm1402095R
ER  - 

@article{
author = "Rakić, Tijana and Jovanović, Marko and Tumpa, Anja and Jančić-Stojanović, Biljana and Medenica, Mirjana",
year = "2014",
abstract = "This paper presents the robust optimization of hydrophilic interaction liquid chromatographic method for the analysis of bisoprolol and its impurities A and C. Chemometric strategy is applied for detailed understanding of system's behavior and establishing the mathematical relationship between investigated factors (acetonitrile content in the mobile phase, pH of the water phase and buffer concentration in the water phase) and chromatographic responses. Grid point search methodology is then performed with the aim to identify the point with satisfactory separation quality for all analyzed substances and to achieve minimal analysis duration. Oversized chromatograms are made creating an extra band broadening for each chromatographic peak corresponding to the value of standard deviation in order to evaluate the incertitude originating from the model uncertainty. On the other hand, the uncertainty originating from the variation of experimental parameters is assessed by simulated experimental design robustness testing. Finally, the obtained robust optimal conditions were: chromatographic column Kinetex HILIC 100Å (100 mm x 4.5 mm, 2.6 mm particle size); mobile phase composed of acetonitrile - water phase (35 mM ammonium acetate, pH 4.9 adjusted with glacial acetic acid) (85:15 v/v); flow rate 1 mL min-1, column temperature 30°C and UV detection at 254 nm., U ovom radu prikazana je optimizacija metode tečne hromatografije hidrofilnih interakcija za analizu bisoprolola i njegovih nečistoća A i C uz procenu mogućnosti variranja položaja pikova. Primenjena je hemometrijska strategija za detaljno razumevanje ponašanja sistema i uspostavljanje matematičke veze između ispitivanih faktora (sadržaj acetonitrila u mobilnoj fazi, pH vrednost vodene faze i koncentracija pufera u vodenoj fazi) i hromatografskih odgovora. Enumerativna tehnika optimizacije upotrebljena je za identifikaciju tačke koja pokazuje zadovoljavajući kvalitet razdvajanja svih ispitivanih supstanci i minimalno vreme trajanja analize. Kreirani su prošireni hromatogrami širenjem pikova svih ispitivanih supstanci za vrednosti standardne devijacije kako bi se procenila mogućnost greške odgovora koja potiče iz greške matematičkog modela. Mogućnost greške koja potiče iz greške u podešavanju eksperimentalnih parametara procenjena je simuliranim testiranjem robusnosti primenom eksperimentalnog dizajna. Konačno, dobijeni optimalni uslovi bili su: hromatografska kolona Kinetex HILIC 100Å (100 mm x 4,5 mm, 2,6 mm veličina čestica); mobilna faza sastavljena od smeše acetonitril - vodena faza (35 mM amonijum-acetat, pH 4,9 podešen glacijalnom sirćetnom kiselinom) (85:15 v/v); protok 1 mL min-1, temperatura kolone 30°C i UV detekcija na 254 nm.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Optimization of HILIC method for the analysis of bisoprolol and its impurities considering uncertainties in peak position, Optimizacija HILIC metode za analizu bisoprolola i njegovih nečistoća uz procenu mogućnosti variranja položaja pikova",
volume = "64",
number = "2",
pages = "95-111",
doi = "10.5937/arhfarm1402095R"
}

Rakić, T., Jovanović, M., Tumpa, A., Jančić-Stojanović, B.,& Medenica, M.. (2014). Optimization of HILIC method for the analysis of bisoprolol and its impurities considering uncertainties in peak position. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 64(2), 95-111.
https://doi.org/10.5937/arhfarm1402095R

Rakić T, Jovanović M, Tumpa A, Jančić-Stojanović B, Medenica M. Optimization of HILIC method for the analysis of bisoprolol and its impurities considering uncertainties in peak position. in Arhiv za farmaciju. 2014;64(2):95-111.
doi:10.5937/arhfarm1402095R .

Rakić, Tijana, Jovanović, Marko, Tumpa, Anja, Jančić-Stojanović, Biljana, Medenica, Mirjana, "Optimization of HILIC method for the analysis of bisoprolol and its impurities considering uncertainties in peak position" in Arhiv za farmaciju, 64, no. 2 (2014):95-111,
https://doi.org/10.5937/arhfarm1402095R . .

TY  - JOUR
AU  - Rakić, Tijana
AU  - Kasagić-Vujanović, Irena
AU  - Jovanović, Marko
AU  - Jančić-Stojanović, Biljana
AU  - Ivanović, Darko
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2223
AB  - This paper presents the development and optimization of a liquid chromatographic method for the determination of fluconazole and its impurities by experimental design methodology. Four experimental design types were applied: two-level full factorial design, central composite design, Box-Behnken design, and three-level full factorial design. The advantages and drawbacks of each design are described and detailed statistical evaluation of mathematical models was performed. The central composite design and three-level full factorial design created significantly better models comparing to the other methods. As the central composite design requires a smaller number of experiments, its models were used for theoretical examination of experimental space. Multiobjective optimization aiming to achieve maximal separation of all investigated substances and minimal analysis duration was performed by a grid point search. The defined optimal separation was achieved on a C-18 (125mmx4mm, 5 mu m particle size) column with a mobile phase consisting of acetonitrile and water (5mM ammonium formate) (15:85, v/v); a column temperature of 25 degrees C; a flow rate of 1.2mLmin(-1); and a detection wavelength of 260nm.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Analytical Letters
T1  - Comparison of Full Factorial Design, Central Composite Design, and Box-Behnken Design in Chromatographic Method Development for the Determination of Fluconazole and Its Impurities
VL  - 47
IS  - 8
SP  - 1334
EP  - 1347
DO  - 10.1080/00032719.2013.867503
ER  - 

@article{
author = "Rakić, Tijana and Kasagić-Vujanović, Irena and Jovanović, Marko and Jančić-Stojanović, Biljana and Ivanović, Darko",
year = "2014",
abstract = "This paper presents the development and optimization of a liquid chromatographic method for the determination of fluconazole and its impurities by experimental design methodology. Four experimental design types were applied: two-level full factorial design, central composite design, Box-Behnken design, and three-level full factorial design. The advantages and drawbacks of each design are described and detailed statistical evaluation of mathematical models was performed. The central composite design and three-level full factorial design created significantly better models comparing to the other methods. As the central composite design requires a smaller number of experiments, its models were used for theoretical examination of experimental space. Multiobjective optimization aiming to achieve maximal separation of all investigated substances and minimal analysis duration was performed by a grid point search. The defined optimal separation was achieved on a C-18 (125mmx4mm, 5 mu m particle size) column with a mobile phase consisting of acetonitrile and water (5mM ammonium formate) (15:85, v/v); a column temperature of 25 degrees C; a flow rate of 1.2mLmin(-1); and a detection wavelength of 260nm.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Analytical Letters",
title = "Comparison of Full Factorial Design, Central Composite Design, and Box-Behnken Design in Chromatographic Method Development for the Determination of Fluconazole and Its Impurities",
volume = "47",
number = "8",
pages = "1334-1347",
doi = "10.1080/00032719.2013.867503"
}

Rakić, T., Kasagić-Vujanović, I., Jovanović, M., Jančić-Stojanović, B.,& Ivanović, D.. (2014). Comparison of Full Factorial Design, Central Composite Design, and Box-Behnken Design in Chromatographic Method Development for the Determination of Fluconazole and Its Impurities. in Analytical Letters
Taylor & Francis Inc, Philadelphia., 47(8), 1334-1347.
https://doi.org/10.1080/00032719.2013.867503

Rakić T, Kasagić-Vujanović I, Jovanović M, Jančić-Stojanović B, Ivanović D. Comparison of Full Factorial Design, Central Composite Design, and Box-Behnken Design in Chromatographic Method Development for the Determination of Fluconazole and Its Impurities. in Analytical Letters. 2014;47(8):1334-1347.
doi:10.1080/00032719.2013.867503 .

Rakić, Tijana, Kasagić-Vujanović, Irena, Jovanović, Marko, Jančić-Stojanović, Biljana, Ivanović, Darko, "Comparison of Full Factorial Design, Central Composite Design, and Box-Behnken Design in Chromatographic Method Development for the Determination of Fluconazole and Its Impurities" in Analytical Letters, 47, no. 8 (2014):1334-1347,
https://doi.org/10.1080/00032719.2013.867503 . .

TY  - JOUR
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
AU  - Ivanović, Darko
AU  - Medenica, Mirjana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2191
AB  - Hydrophilic interaction liquid chromatography (HILIC) has emerged in recent years as a valuable alternative to reversed-phase liquid chromatography in the analysis of polar compounds. Research in HILIC is divided into two directions: the assessment of the retention mechanism and retention behavior, and the development of HILIC methods. In this work, four polar neutral analytes (iohexol and its related compounds A, B, and C) were analyzed on two silica and two diol columns in HILIC mode with the aim to investigate thoroughly the retention mechanisms and retention behavior of polar neutral compounds on these four columns. The adsorption and partition contribution to the overall HILIC retention mechanism was investigated by fitting the retention data to linear (adsorption and partition) and nonlinear (mixed-retention and quadratic) theoretical models. On the other hand, the establishment of empirical second-order polynomial retention models on the basis of D-optimal design made possible the estimation of the simultaneous influence of several mobile-phase-related factors. Furthermore, these models were also used as the basis for the application of indirect modeling of the selectivity factor and a grid point search approach in order to achieve the optimal separation of analytes. After the optimization goals had been set, the grids were searched and the optimal conditions were identified. Finally, the optimized method was subjected to validation.
PB  - Springer Heidelberg, Heidelberg
T2  - Analytical and Bioanalytical Chemistry
T1  - Retention mechanism assessment and method development for the analysis of iohexol and its related compounds in hydrophilic interaction liquid chromatography
VL  - 406
IS  - 17
SP  - 4217
EP  - 4232
DO  - 10.1007/s00216-014-7808-6
ER  - 

@article{
author = "Jovanović, Marko and Rakić, Tijana and Jančić-Stojanović, Biljana and Ivanović, Darko and Medenica, Mirjana",
year = "2014",
abstract = "Hydrophilic interaction liquid chromatography (HILIC) has emerged in recent years as a valuable alternative to reversed-phase liquid chromatography in the analysis of polar compounds. Research in HILIC is divided into two directions: the assessment of the retention mechanism and retention behavior, and the development of HILIC methods. In this work, four polar neutral analytes (iohexol and its related compounds A, B, and C) were analyzed on two silica and two diol columns in HILIC mode with the aim to investigate thoroughly the retention mechanisms and retention behavior of polar neutral compounds on these four columns. The adsorption and partition contribution to the overall HILIC retention mechanism was investigated by fitting the retention data to linear (adsorption and partition) and nonlinear (mixed-retention and quadratic) theoretical models. On the other hand, the establishment of empirical second-order polynomial retention models on the basis of D-optimal design made possible the estimation of the simultaneous influence of several mobile-phase-related factors. Furthermore, these models were also used as the basis for the application of indirect modeling of the selectivity factor and a grid point search approach in order to achieve the optimal separation of analytes. After the optimization goals had been set, the grids were searched and the optimal conditions were identified. Finally, the optimized method was subjected to validation.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Analytical and Bioanalytical Chemistry",
title = "Retention mechanism assessment and method development for the analysis of iohexol and its related compounds in hydrophilic interaction liquid chromatography",
volume = "406",
number = "17",
pages = "4217-4232",
doi = "10.1007/s00216-014-7808-6"
}

Jovanović, M., Rakić, T., Jančić-Stojanović, B., Ivanović, D.,& Medenica, M.. (2014). Retention mechanism assessment and method development for the analysis of iohexol and its related compounds in hydrophilic interaction liquid chromatography. in Analytical and Bioanalytical Chemistry
Springer Heidelberg, Heidelberg., 406(17), 4217-4232.
https://doi.org/10.1007/s00216-014-7808-6

Jovanović M, Rakić T, Jančić-Stojanović B, Ivanović D, Medenica M. Retention mechanism assessment and method development for the analysis of iohexol and its related compounds in hydrophilic interaction liquid chromatography. in Analytical and Bioanalytical Chemistry. 2014;406(17):4217-4232.
doi:10.1007/s00216-014-7808-6 .

Jovanović, Marko, Rakić, Tijana, Jančić-Stojanović, Biljana, Ivanović, Darko, Medenica, Mirjana, "Retention mechanism assessment and method development for the analysis of iohexol and its related compounds in hydrophilic interaction liquid chromatography" in Analytical and Bioanalytical Chemistry, 406, no. 17 (2014):4217-4232,
https://doi.org/10.1007/s00216-014-7808-6 . .

TY  - JOUR
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2151
AB  - Hydrophilic interaction liquid chromatography (HILIC) has found application in the determination of polar molecules. This alternative type of chromatography has become increasingly popular in the last five years and a considerable number of articles regarding the elucidation of its retention mechanisms and the development of methods are available. In order to achieve these goals, various types of theoretical and empirical mathematical models were utilized. However, the knowledge obtained from these models was the subject of various interpretations. The goal of this article is to list and discuss the papers in which these models were used in HILIC and give proper theoretical background of the models. In general, theoretical models in HILIC were applied in order to acquire the knowledge of dominant processes in the retention mechanism, retention prediction, and quantitative description of the influence of mobile phase-related factors on the retention and selectivity of the analytes on different types of stationary phases. In addition, empirical models were used for detailed assessment of the retention behavior in terms of both single factor and factor interactions influence on analyte retention and selectivity. Furthermore, they have also shown a great potential in the optimization of HILIC methods in the method development process.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Instrumentation Science & Technology
T1  - Theoretical and empirical models in hydrophilic interaction liquid chromatography
VL  - 42
IS  - 3
SP  - 230
EP  - 266
DO  - 10.1080/10739149.2013.865214
ER  - 

@article{
author = "Jovanović, Marko and Rakić, Tijana and Jančić-Stojanović, Biljana",
year = "2014",
abstract = "Hydrophilic interaction liquid chromatography (HILIC) has found application in the determination of polar molecules. This alternative type of chromatography has become increasingly popular in the last five years and a considerable number of articles regarding the elucidation of its retention mechanisms and the development of methods are available. In order to achieve these goals, various types of theoretical and empirical mathematical models were utilized. However, the knowledge obtained from these models was the subject of various interpretations. The goal of this article is to list and discuss the papers in which these models were used in HILIC and give proper theoretical background of the models. In general, theoretical models in HILIC were applied in order to acquire the knowledge of dominant processes in the retention mechanism, retention prediction, and quantitative description of the influence of mobile phase-related factors on the retention and selectivity of the analytes on different types of stationary phases. In addition, empirical models were used for detailed assessment of the retention behavior in terms of both single factor and factor interactions influence on analyte retention and selectivity. Furthermore, they have also shown a great potential in the optimization of HILIC methods in the method development process.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Instrumentation Science & Technology",
title = "Theoretical and empirical models in hydrophilic interaction liquid chromatography",
volume = "42",
number = "3",
pages = "230-266",
doi = "10.1080/10739149.2013.865214"
}

Jovanović, M., Rakić, T.,& Jančić-Stojanović, B.. (2014). Theoretical and empirical models in hydrophilic interaction liquid chromatography. in Instrumentation Science & Technology
Taylor & Francis Inc, Philadelphia., 42(3), 230-266.
https://doi.org/10.1080/10739149.2013.865214

Jovanović M, Rakić T, Jančić-Stojanović B. Theoretical and empirical models in hydrophilic interaction liquid chromatography. in Instrumentation Science & Technology. 2014;42(3):230-266.
doi:10.1080/10739149.2013.865214 .

Jovanović, Marko, Rakić, Tijana, Jančić-Stojanović, Biljana, "Theoretical and empirical models in hydrophilic interaction liquid chromatography" in Instrumentation Science & Technology, 42, no. 3 (2014):230-266,
https://doi.org/10.1080/10739149.2013.865214 . .

TY  - JOUR
AU  - Rakić, Tijana
AU  - Jovanović, Marko
AU  - Dumić, Aleksandra
AU  - Pekić, Marina
AU  - Ribić, Sanja
AU  - Jančić-Stojanović, Biljana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1982
AB  - This paper presents multiobjective optimization of complex mixtures separation in hydrophilic interaction liquid chromatography (HILIC). The selected model mixture consisted of five psychotropic drugs: clozapine, thioridazine, sulpiride, pheniramine and lamotrigine. Three factors related to the mobile phase composition (acetonitrile content, pH of the water phase and concentration of ammonium acetate) were optimized in order to achieve the following goals: maximal separation quality, minimal total analysis duration and robustness of an optimum. The consideration of robustness in early phases of the method development provides reliable methods with low risk for failure in validation phase. The simultaneous optimization of all goals was achieved by multiple threshold approach combined with grid point search. The identified optimal separation conditions (acetonitrile content 83%, pH of the water phase 3.5 and ammonium acetate content in water phase 14 mM) were experimentally verified.
PB  - Slovensko Kemijsko Drustvo, Ljubljana
T2  - Acta Chimica Slovenica
T1  - Robust Optimization of Psychotropic Drug Mixture Separation in Hydrophilic Interaction Liquid Chromatography
VL  - 60
IS  - 2
SP  - 411
EP  - 415
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1982
ER  - 

@article{
author = "Rakić, Tijana and Jovanović, Marko and Dumić, Aleksandra and Pekić, Marina and Ribić, Sanja and Jančić-Stojanović, Biljana",
year = "2013",
abstract = "This paper presents multiobjective optimization of complex mixtures separation in hydrophilic interaction liquid chromatography (HILIC). The selected model mixture consisted of five psychotropic drugs: clozapine, thioridazine, sulpiride, pheniramine and lamotrigine. Three factors related to the mobile phase composition (acetonitrile content, pH of the water phase and concentration of ammonium acetate) were optimized in order to achieve the following goals: maximal separation quality, minimal total analysis duration and robustness of an optimum. The consideration of robustness in early phases of the method development provides reliable methods with low risk for failure in validation phase. The simultaneous optimization of all goals was achieved by multiple threshold approach combined with grid point search. The identified optimal separation conditions (acetonitrile content 83%, pH of the water phase 3.5 and ammonium acetate content in water phase 14 mM) were experimentally verified.",
publisher = "Slovensko Kemijsko Drustvo, Ljubljana",
journal = "Acta Chimica Slovenica",
title = "Robust Optimization of Psychotropic Drug Mixture Separation in Hydrophilic Interaction Liquid Chromatography",
volume = "60",
number = "2",
pages = "411-415",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1982"
}

Rakić, T., Jovanović, M., Dumić, A., Pekić, M., Ribić, S.,& Jančić-Stojanović, B.. (2013). Robust Optimization of Psychotropic Drug Mixture Separation in Hydrophilic Interaction Liquid Chromatography. in Acta Chimica Slovenica
Slovensko Kemijsko Drustvo, Ljubljana., 60(2), 411-415.
https://hdl.handle.net/21.15107/rcub_farfar_1982

Rakić T, Jovanović M, Dumić A, Pekić M, Ribić S, Jančić-Stojanović B. Robust Optimization of Psychotropic Drug Mixture Separation in Hydrophilic Interaction Liquid Chromatography. in Acta Chimica Slovenica. 2013;60(2):411-415.
https://hdl.handle.net/21.15107/rcub_farfar_1982 .

Rakić, Tijana, Jovanović, Marko, Dumić, Aleksandra, Pekić, Marina, Ribić, Sanja, Jančić-Stojanović, Biljana, "Robust Optimization of Psychotropic Drug Mixture Separation in Hydrophilic Interaction Liquid Chromatography" in Acta Chimica Slovenica, 60, no. 2 (2013):411-415,
https://hdl.handle.net/21.15107/rcub_farfar_1982 .

TY  - JOUR
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
AU  - Jovanović, Marko
AU  - Malenović, Anđelija
AU  - Ivanović, Darko
AU  - Medenica, Mirjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3419
AB  - This paper investigates the ability of seven chromatographic response functions to measure the quality of chromatograms obtained in hydrophilic interaction liquid chromatography (HILIC). First, the functions were tested on a set of simulated chromatograms and differences in their mathematical design were discussed. Second, the functions were evaluated on the experimentally obtained chromatograms in HILIC analysis of model mixture consisted of beta agonists and antagonists. The ranking of chromatograms obtained by different functions was significantly different, implying that the accuracy of the optimization procedure is strongly dependent on the function that was selected as an output. Investigation of potential drawbacks of each function was conducted and general recommendations concerning the use of chromatographic response functions in optimization strategies are proposed.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Analytical Letters
T1  - Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System
VL  - 46
IS  - 8
SP  - 1198
EP  - 1212
DO  - 10.1080/00032719.2012.755689
ER  - 

@article{
author = "Rakić, Tijana and Jančić-Stojanović, Biljana and Jovanović, Marko and Malenović, Anđelija and Ivanović, Darko and Medenica, Mirjana",
year = "2013",
abstract = "This paper investigates the ability of seven chromatographic response functions to measure the quality of chromatograms obtained in hydrophilic interaction liquid chromatography (HILIC). First, the functions were tested on a set of simulated chromatograms and differences in their mathematical design were discussed. Second, the functions were evaluated on the experimentally obtained chromatograms in HILIC analysis of model mixture consisted of beta agonists and antagonists. The ranking of chromatograms obtained by different functions was significantly different, implying that the accuracy of the optimization procedure is strongly dependent on the function that was selected as an output. Investigation of potential drawbacks of each function was conducted and general recommendations concerning the use of chromatographic response functions in optimization strategies are proposed.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Analytical Letters",
title = "Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System",
volume = "46",
number = "8",
pages = "1198-1212",
doi = "10.1080/00032719.2012.755689"
}

Rakić, T., Jančić-Stojanović, B., Jovanović, M., Malenović, A., Ivanović, D.,& Medenica, M.. (2013). Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System. in Analytical Letters
Taylor & Francis Inc, Philadelphia., 46(8), 1198-1212.
https://doi.org/10.1080/00032719.2012.755689

Rakić T, Jančić-Stojanović B, Jovanović M, Malenović A, Ivanović D, Medenica M. Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System. in Analytical Letters. 2013;46(8):1198-1212.
doi:10.1080/00032719.2012.755689 .

Rakić, Tijana, Jančić-Stojanović, Biljana, Jovanović, Marko, Malenović, Anđelija, Ivanović, Darko, Medenica, Mirjana, "Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System" in Analytical Letters, 46, no. 8 (2013):1198-1212,
https://doi.org/10.1080/00032719.2012.755689 . .

TY  - CHAP
AU  - Jančić-Stojanović, Biljana
AU  - Rakić, Tijana
AU  - Malenović, Anđelija
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2032
AB  - The quality of liquid chromatographic methods developed for pharmaceutical applications is strongly dependent on their robustness. The robustness issue requires a studious strategy where many important aspects regarding both the optimization and validation phases must be considered; therefore, these aspects will be presented in this paper. The first step in evaluating the robustness is robustness screening during the method optimization. In this phase, important chromatographic factors (organic modifier content, pH of the mobile phase, column temperature, etc.) and their influence on the chromatographic parameters should be examined. A different type of response surface design could be utilized in this step, and its application allows the examination of the response surface to identify the robust regions, such as the maximum, minimum or inflection point. Total robustness is achieved if the response is robust for all of the investigated factors. However, if total robustness does not occur, the quality of the chromatographic method can be expressed by partial robustness. Additionally, the robustness of the selected chromatographic optimum can be analyzed by estimating the robustness criterion. This approach is based on calculating the derivatives of selected chromatographic responses with respect to the investigated factors and then monitoring the rate of change of the response while the factors deviate within the expected range. The second level of the robustness evaluation is robustness testing at the beginning of the method validation process. Primarily, this phase includes defining the factors that are to be examined and their levels. It is desirable to select as many factors as possible (factors related to the mobile phase, stationary phase, sample preparation, equipment, etc.) and set their levels as narrow regions around the nominal level. This step is followed by selecting an adequate experimental design that allows the estimation of a relatively great number of factors through a relatively small number of experiments (usually fractional factorial or Plackett-Burman design). The final step of this level consists of analyzing the obtained results and interpreting the significance of the effects. The methods commonly applied for estimating the effects are graphical analysis (involving normal and half-normal probability plots) and statistical analysis (including the algorithm of Dong and error estimation based on a priori declared negligible effects). Lastly, the information extracted from the robustness testing enables relatively simple definition of system suitability tests, which is an integral part of routine application of any chromatographic method. The systematic robustness evaluation is applied to an experimental example for analyzing beta blockers and agonists in a hydrophilic interaction liquid chromatography experiment. It can be concluded that evaluating the robustness of the chromatographic method in the right way provides a lot of significant data, which enable safe method application and transfer.
PB  - Nova Science Publishers, Inc.
T2  - Liquid Chromatography: Principles, Technology and Applications
T1  - Robustness of liquid chromatographic method: How to achieve it and how to confirm it?
SP  - 57
EP  - 98
UR  - https://hdl.handle.net/21.15107/rcub_farfar_2032
ER  - 

@inbook{
author = "Jančić-Stojanović, Biljana and Rakić, Tijana and Malenović, Anđelija",
year = "2013",
abstract = "The quality of liquid chromatographic methods developed for pharmaceutical applications is strongly dependent on their robustness. The robustness issue requires a studious strategy where many important aspects regarding both the optimization and validation phases must be considered; therefore, these aspects will be presented in this paper. The first step in evaluating the robustness is robustness screening during the method optimization. In this phase, important chromatographic factors (organic modifier content, pH of the mobile phase, column temperature, etc.) and their influence on the chromatographic parameters should be examined. A different type of response surface design could be utilized in this step, and its application allows the examination of the response surface to identify the robust regions, such as the maximum, minimum or inflection point. Total robustness is achieved if the response is robust for all of the investigated factors. However, if total robustness does not occur, the quality of the chromatographic method can be expressed by partial robustness. Additionally, the robustness of the selected chromatographic optimum can be analyzed by estimating the robustness criterion. This approach is based on calculating the derivatives of selected chromatographic responses with respect to the investigated factors and then monitoring the rate of change of the response while the factors deviate within the expected range. The second level of the robustness evaluation is robustness testing at the beginning of the method validation process. Primarily, this phase includes defining the factors that are to be examined and their levels. It is desirable to select as many factors as possible (factors related to the mobile phase, stationary phase, sample preparation, equipment, etc.) and set their levels as narrow regions around the nominal level. This step is followed by selecting an adequate experimental design that allows the estimation of a relatively great number of factors through a relatively small number of experiments (usually fractional factorial or Plackett-Burman design). The final step of this level consists of analyzing the obtained results and interpreting the significance of the effects. The methods commonly applied for estimating the effects are graphical analysis (involving normal and half-normal probability plots) and statistical analysis (including the algorithm of Dong and error estimation based on a priori declared negligible effects). Lastly, the information extracted from the robustness testing enables relatively simple definition of system suitability tests, which is an integral part of routine application of any chromatographic method. The systematic robustness evaluation is applied to an experimental example for analyzing beta blockers and agonists in a hydrophilic interaction liquid chromatography experiment. It can be concluded that evaluating the robustness of the chromatographic method in the right way provides a lot of significant data, which enable safe method application and transfer.",
publisher = "Nova Science Publishers, Inc.",
journal = "Liquid Chromatography: Principles, Technology and Applications",
booktitle = "Robustness of liquid chromatographic method: How to achieve it and how to confirm it?",
pages = "57-98",
url = "https://hdl.handle.net/21.15107/rcub_farfar_2032"
}

Jančić-Stojanović, B., Rakić, T.,& Malenović, A.. (2013). Robustness of liquid chromatographic method: How to achieve it and how to confirm it?. in Liquid Chromatography: Principles, Technology and Applications
Nova Science Publishers, Inc.., 57-98.
https://hdl.handle.net/21.15107/rcub_farfar_2032

Jančić-Stojanović B, Rakić T, Malenović A. Robustness of liquid chromatographic method: How to achieve it and how to confirm it?. in Liquid Chromatography: Principles, Technology and Applications. 2013;:57-98.
https://hdl.handle.net/21.15107/rcub_farfar_2032 .

Jančić-Stojanović, Biljana, Rakić, Tijana, Malenović, Anđelija, "Robustness of liquid chromatographic method: How to achieve it and how to confirm it?" in Liquid Chromatography: Principles, Technology and Applications (2013):57-98,
https://hdl.handle.net/21.15107/rcub_farfar_2032 .

TY  - JOUR
AU  - Jančić-Stojanović, Biljana
AU  - Rakić, Tijana
AU  - Slavković, B
AU  - Kostić, Nada
AU  - Vemić, Ana
AU  - Malenović, Anđelija
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2025
AB  - Method validation presents a detailed investigation of analytical method and provision of the evidence that the method, when correctly applied, produces results that fit to the purpose. In order to achieve the method validation scope efficiently, experimental design presents a very useful tool. The greatest benefits of such approach could be seen in robustness testing through the provision of very useful data about the control of the chromatographic system during the routine application. In this paper, robustness testing of the LC method proposed for the determination of raloxifene hydrochloride and its four impurities was done employing Plackett-Burman design. Applying this design, the effect of five real factors (acetonitrile content, sodium dodecyl sulfate content, column temperature, pH of the mobile phase and flow rate) on the corresponding resolution factors was investigated through twelve experiments. Furthermore, the insignificance intervals for significant factors were calculated and the parameters for system suitability tests were defined. Eventually, the other validation parameters were tested and the effectiveness of the proposed analytical method with a high degree of accuracy was confirmed.
PB  - Xi'an Jiaotong University
T2  - Journal of Pharmaceutical Analysis
T1  - Systematical approach in evaluation of LC method for determination of raloxifene hydrochloride and its impurities employing experimental design
VL  - 3
IS  - 1
SP  - 45
EP  - 52
DO  - 10.1016/j.jpha.2012.09.007
ER  - 

@article{
author = "Jančić-Stojanović, Biljana and Rakić, Tijana and Slavković, B and Kostić, Nada and Vemić, Ana and Malenović, Anđelija",
year = "2013",
abstract = "Method validation presents a detailed investigation of analytical method and provision of the evidence that the method, when correctly applied, produces results that fit to the purpose. In order to achieve the method validation scope efficiently, experimental design presents a very useful tool. The greatest benefits of such approach could be seen in robustness testing through the provision of very useful data about the control of the chromatographic system during the routine application. In this paper, robustness testing of the LC method proposed for the determination of raloxifene hydrochloride and its four impurities was done employing Plackett-Burman design. Applying this design, the effect of five real factors (acetonitrile content, sodium dodecyl sulfate content, column temperature, pH of the mobile phase and flow rate) on the corresponding resolution factors was investigated through twelve experiments. Furthermore, the insignificance intervals for significant factors were calculated and the parameters for system suitability tests were defined. Eventually, the other validation parameters were tested and the effectiveness of the proposed analytical method with a high degree of accuracy was confirmed.",
publisher = "Xi'an Jiaotong University",
journal = "Journal of Pharmaceutical Analysis",
title = "Systematical approach in evaluation of LC method for determination of raloxifene hydrochloride and its impurities employing experimental design",
volume = "3",
number = "1",
pages = "45-52",
doi = "10.1016/j.jpha.2012.09.007"
}

Jančić-Stojanović, B., Rakić, T., Slavković, B., Kostić, N., Vemić, A.,& Malenović, A.. (2013). Systematical approach in evaluation of LC method for determination of raloxifene hydrochloride and its impurities employing experimental design. in Journal of Pharmaceutical Analysis
Xi'an Jiaotong University., 3(1), 45-52.
https://doi.org/10.1016/j.jpha.2012.09.007

Jančić-Stojanović B, Rakić T, Slavković B, Kostić N, Vemić A, Malenović A. Systematical approach in evaluation of LC method for determination of raloxifene hydrochloride and its impurities employing experimental design. in Journal of Pharmaceutical Analysis. 2013;3(1):45-52.
doi:10.1016/j.jpha.2012.09.007 .

Jančić-Stojanović, Biljana, Rakić, Tijana, Slavković, B, Kostić, Nada, Vemić, Ana, Malenović, Anđelija, "Systematical approach in evaluation of LC method for determination of raloxifene hydrochloride and its impurities employing experimental design" in Journal of Pharmaceutical Analysis, 3, no. 1 (2013):45-52,
https://doi.org/10.1016/j.jpha.2012.09.007 . .

TY  - JOUR
AU  - Kasagić-Vujanović, Irena
AU  - Malenović, Anđelija
AU  - Jovanović, Marko
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
AU  - Ivanović, Darko
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1920
AB  - This paper presents the chemometrically assisted optimization and validation of the RP-HPLC method intended for the quantitative analysis of itraconazole and its impurities in pharmaceutical dosage forms. To reach the desired chromatographic resolution with a limited number of experiments in a minimum amount of time, Box-Behnken design was used to simultaneously optimize some important chromatographic parameters, such as the acetonitrile content in the mobile phase, pH of the aqueous phase and the column temperature. Separation between itraconazole and impurity F was identified as critical and selected as a response during the optimization. The set optimal mobile phase composition was acetonitrile/water pH 2.5 adjusted with o-phosphoric acid (50:50, V/V). Separations were performed on a Zorbax Eclipse XDB-C18, 4.6 x 150 mm, 5 mu m particle size column with the flow rate 1 mL min(-1), column temperature set at 30 degrees C and UV detection at 256 nm. The established method was then subjected to method validation and the required validation parameters were tested. For the robustness evaluation, fractional factorial 2(4-1) design was utilized and factors that might significantly affect the system performance were defined. As other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of itraconazole, its impurities B and F in any laboratory under different circumstances has been proven.
PB  - Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb
T2  - Acta Pharmaceutica
T1  - Chemometrically assissted optimization and validation of RP-HPLC method for the analysis of itraconazole and its impurities
VL  - 63
IS  - 2
SP  - 159
EP  - 173
DO  - 10.2478/acph-2013-0015
ER  - 

@article{
author = "Kasagić-Vujanović, Irena and Malenović, Anđelija and Jovanović, Marko and Rakić, Tijana and Jančić-Stojanović, Biljana and Ivanović, Darko",
year = "2013",
abstract = "This paper presents the chemometrically assisted optimization and validation of the RP-HPLC method intended for the quantitative analysis of itraconazole and its impurities in pharmaceutical dosage forms. To reach the desired chromatographic resolution with a limited number of experiments in a minimum amount of time, Box-Behnken design was used to simultaneously optimize some important chromatographic parameters, such as the acetonitrile content in the mobile phase, pH of the aqueous phase and the column temperature. Separation between itraconazole and impurity F was identified as critical and selected as a response during the optimization. The set optimal mobile phase composition was acetonitrile/water pH 2.5 adjusted with o-phosphoric acid (50:50, V/V). Separations were performed on a Zorbax Eclipse XDB-C18, 4.6 x 150 mm, 5 mu m particle size column with the flow rate 1 mL min(-1), column temperature set at 30 degrees C and UV detection at 256 nm. The established method was then subjected to method validation and the required validation parameters were tested. For the robustness evaluation, fractional factorial 2(4-1) design was utilized and factors that might significantly affect the system performance were defined. As other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of itraconazole, its impurities B and F in any laboratory under different circumstances has been proven.",
publisher = "Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb",
journal = "Acta Pharmaceutica",
title = "Chemometrically assissted optimization and validation of RP-HPLC method for the analysis of itraconazole and its impurities",
volume = "63",
number = "2",
pages = "159-173",
doi = "10.2478/acph-2013-0015"
}

Kasagić-Vujanović, I., Malenović, A., Jovanović, M., Rakić, T., Jančić-Stojanović, B.,& Ivanović, D.. (2013). Chemometrically assissted optimization and validation of RP-HPLC method for the analysis of itraconazole and its impurities. in Acta Pharmaceutica
Hrvatsko Farmaceutsko Drustov (HFD)-Croation Pharmaceutical Soc, Zagreb., 63(2), 159-173.
https://doi.org/10.2478/acph-2013-0015

Kasagić-Vujanović I, Malenović A, Jovanović M, Rakić T, Jančić-Stojanović B, Ivanović D. Chemometrically assissted optimization and validation of RP-HPLC method for the analysis of itraconazole and its impurities. in Acta Pharmaceutica. 2013;63(2):159-173.
doi:10.2478/acph-2013-0015 .

Kasagić-Vujanović, Irena, Malenović, Anđelija, Jovanović, Marko, Rakić, Tijana, Jančić-Stojanović, Biljana, Ivanović, Darko, "Chemometrically assissted optimization and validation of RP-HPLC method for the analysis of itraconazole and its impurities" in Acta Pharmaceutica, 63, no. 2 (2013):159-173,
https://doi.org/10.2478/acph-2013-0015 . .

TY  - JOUR
AU  - Jovanović, Marko
AU  - Jančić-Stojanović, Biljana
AU  - Rakić, Tijana
AU  - Malenović, Anđelija
AU  - Ivanović, Darko
AU  - Medenica, Mirjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2001
AB  - Five different columns (two silica, two cyanopropyl and one diol) were investigated in hydrophilic interaction liquid chromatography (HILIC). For the assessment of columns behavior in HILIC mode, six basic drugs (lamotrigine, thioridazine, clozapine, chlorpheniramine, pheniramine and sulpiride) were chosen. The assessment of the influence of the concentration of organic modifier on analytes' retention on each column was provided by fitting the retention data into theoretical models. Utilizing the statistical analysis, the selection of the model that provides better prediction of the retention behavior was enabled. Dual RP-HILIC mechanism was suggested on cyanopropyl and diol columns, therefore the transition points between the two mechanisms on these columns were calculated. Furthermore, in order to investigate the impact of three factors simultaneously on the retention behavior of the analyzed substances on Betasil Silica column, chemometrically-aided empirical models were built. The experiments were conducted according to the matrix of Box-Behnken design and on the basis of the retention data, six quadratic models were obtained and their adequacy was confirmed using ANOVA test. The obtained coefficients of quadratic models enabled the elucidation of both single factor and factor interactions influence. This was also graphically presented in 3D response surface plots.
PB  - Versita, Warsaw
T2  - Central European Journal of Chemistry
T1  - Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography
VL  - 11
IS  - 7
SP  - 1150
EP  - 1162
DO  - 10.2478/s11532-013-0245-0
ER  - 

@article{
author = "Jovanović, Marko and Jančić-Stojanović, Biljana and Rakić, Tijana and Malenović, Anđelija and Ivanović, Darko and Medenica, Mirjana",
year = "2013",
abstract = "Five different columns (two silica, two cyanopropyl and one diol) were investigated in hydrophilic interaction liquid chromatography (HILIC). For the assessment of columns behavior in HILIC mode, six basic drugs (lamotrigine, thioridazine, clozapine, chlorpheniramine, pheniramine and sulpiride) were chosen. The assessment of the influence of the concentration of organic modifier on analytes' retention on each column was provided by fitting the retention data into theoretical models. Utilizing the statistical analysis, the selection of the model that provides better prediction of the retention behavior was enabled. Dual RP-HILIC mechanism was suggested on cyanopropyl and diol columns, therefore the transition points between the two mechanisms on these columns were calculated. Furthermore, in order to investigate the impact of three factors simultaneously on the retention behavior of the analyzed substances on Betasil Silica column, chemometrically-aided empirical models were built. The experiments were conducted according to the matrix of Box-Behnken design and on the basis of the retention data, six quadratic models were obtained and their adequacy was confirmed using ANOVA test. The obtained coefficients of quadratic models enabled the elucidation of both single factor and factor interactions influence. This was also graphically presented in 3D response surface plots.",
publisher = "Versita, Warsaw",
journal = "Central European Journal of Chemistry",
title = "Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography",
volume = "11",
number = "7",
pages = "1150-1162",
doi = "10.2478/s11532-013-0245-0"
}

Jovanović, M., Jančić-Stojanović, B., Rakić, T., Malenović, A., Ivanović, D.,& Medenica, M.. (2013). Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography. in Central European Journal of Chemistry
Versita, Warsaw., 11(7), 1150-1162.
https://doi.org/10.2478/s11532-013-0245-0

Jovanović M, Jančić-Stojanović B, Rakić T, Malenović A, Ivanović D, Medenica M. Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography. in Central European Journal of Chemistry. 2013;11(7):1150-1162.
doi:10.2478/s11532-013-0245-0 .

Jovanović, Marko, Jančić-Stojanović, Biljana, Rakić, Tijana, Malenović, Anđelija, Ivanović, Darko, Medenica, Mirjana, "Five different columns in the analysis of basic drugs in hydrophilic interaction liquid chromatography" in Central European Journal of Chemistry, 11, no. 7 (2013):1150-1162,
https://doi.org/10.2478/s11532-013-0245-0 . .

TY  - JOUR
AU  - Rakić, Tijana
AU  - Jančić-Stojanović, Biljana
AU  - Jovanović, Marko
AU  - Malenović, Anđelija
AU  - Ivanović, Darko
AU  - Medenica, Mirjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2003
AB  - This paper investigates the ability of seven chromatographic response functions to measure the quality of chromatograms obtained in hydrophilic interaction liquid chromatography (HILIC). First, the functions were tested on a set of simulated chromatograms and differences in their mathematical design were discussed. Second, the functions were evaluated on the experimentally obtained chromatograms in HILIC analysis of model mixture consisted of beta agonists and antagonists. The ranking of chromatograms obtained by different functions was significantly different, implying that the accuracy of the optimization procedure is strongly dependent on the function that was selected as an output. Investigation of potential drawbacks of each function was conducted and general recommendations concerning the use of chromatographic response functions in optimization strategies are proposed.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Analytical Letters
T1  - Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System
VL  - 46
IS  - 8
SP  - 1198
EP  - 1212
DO  - 10.1080/00032719.2012.755689
ER  - 

@article{
author = "Rakić, Tijana and Jančić-Stojanović, Biljana and Jovanović, Marko and Malenović, Anđelija and Ivanović, Darko and Medenica, Mirjana",
year = "2013",
abstract = "This paper investigates the ability of seven chromatographic response functions to measure the quality of chromatograms obtained in hydrophilic interaction liquid chromatography (HILIC). First, the functions were tested on a set of simulated chromatograms and differences in their mathematical design were discussed. Second, the functions were evaluated on the experimentally obtained chromatograms in HILIC analysis of model mixture consisted of beta agonists and antagonists. The ranking of chromatograms obtained by different functions was significantly different, implying that the accuracy of the optimization procedure is strongly dependent on the function that was selected as an output. Investigation of potential drawbacks of each function was conducted and general recommendations concerning the use of chromatographic response functions in optimization strategies are proposed.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Analytical Letters",
title = "Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System",
volume = "46",
number = "8",
pages = "1198-1212",
doi = "10.1080/00032719.2012.755689"
}

Rakić, T., Jančić-Stojanović, B., Jovanović, M., Malenović, A., Ivanović, D.,& Medenica, M.. (2013). Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System. in Analytical Letters
Taylor & Francis Inc, Philadelphia., 46(8), 1198-1212.
https://doi.org/10.1080/00032719.2012.755689

Rakić T, Jančić-Stojanović B, Jovanović M, Malenović A, Ivanović D, Medenica M. Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System. in Analytical Letters. 2013;46(8):1198-1212.
doi:10.1080/00032719.2012.755689 .

Rakić, Tijana, Jančić-Stojanović, Biljana, Jovanović, Marko, Malenović, Anđelija, Ivanović, Darko, Medenica, Mirjana, "Evaluation of Seven Chromatographic Response Functions on Simulated and Experimentally Obtained Chromatograms in Hydrophilic Interaction Liquid Chromatography System" in Analytical Letters, 46, no. 8 (2013):1198-1212,
https://doi.org/10.1080/00032719.2012.755689 . .