TY  - JOUR
AU  - Colović, Jelena
AU  - Rmandić, Milena
AU  - Malenović, Anđelija
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3310
AB  - In this study robust optimization was applied for the development of a reliable analytical assay for lamotrigine, its impurity A, and impurity G in tablets by chaotropic chromatography. The influence of the critical method parameters (acetonitrile content, concentration of chaotropic agent, and pH of the water phase) on the set of selected critical method attributes (retention factor of impurity A, separation factor between lamotrigine and impurity G, and retention factor of impurity G) is studied by Box-Behnken design. Monte Carlo simulations were applied to propagate the errors originating from the model coefficients' calculation to the selected responses and obtain their predictive distribution. Design space was defined (95%) and a working point selected: 23% of acetonitrile in the mobile phase, 77% of water phase containing 140mM of perchloric acid, and pH of the water phase adjusted to 2.50. Further robustness testing was performed by Plackett-Burman design to evaluate the quantitative performance of the developed method. The obtained models included not only active main effects but also interactions that were identified as active with the aid of an alias matrix approach and examination of resulting alias plots. The method was validated and its reliability for routine pharmaceutical analysis confirmed. [GRAPHICS] .
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Robust Optimization of Chaotropic Chromatography Assay for Lamotrigine and its Two Impurities in Tablets
VL  - 82
IS  - 2
SP  - 565
EP  - 577
DO  - 10.1007/s10337-018-3661-7
ER  - 

@article{
author = "Colović, Jelena and Rmandić, Milena and Malenović, Anđelija",
year = "2019",
abstract = "In this study robust optimization was applied for the development of a reliable analytical assay for lamotrigine, its impurity A, and impurity G in tablets by chaotropic chromatography. The influence of the critical method parameters (acetonitrile content, concentration of chaotropic agent, and pH of the water phase) on the set of selected critical method attributes (retention factor of impurity A, separation factor between lamotrigine and impurity G, and retention factor of impurity G) is studied by Box-Behnken design. Monte Carlo simulations were applied to propagate the errors originating from the model coefficients' calculation to the selected responses and obtain their predictive distribution. Design space was defined (95%) and a working point selected: 23% of acetonitrile in the mobile phase, 77% of water phase containing 140mM of perchloric acid, and pH of the water phase adjusted to 2.50. Further robustness testing was performed by Plackett-Burman design to evaluate the quantitative performance of the developed method. The obtained models included not only active main effects but also interactions that were identified as active with the aid of an alias matrix approach and examination of resulting alias plots. The method was validated and its reliability for routine pharmaceutical analysis confirmed. [GRAPHICS] .",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Robust Optimization of Chaotropic Chromatography Assay for Lamotrigine and its Two Impurities in Tablets",
volume = "82",
number = "2",
pages = "565-577",
doi = "10.1007/s10337-018-3661-7"
}

Colović, J., Rmandić, M.,& Malenović, A.. (2019). Robust Optimization of Chaotropic Chromatography Assay for Lamotrigine and its Two Impurities in Tablets. in Chromatographia
Springer Heidelberg, Heidelberg., 82(2), 565-577.
https://doi.org/10.1007/s10337-018-3661-7

Colović J, Rmandić M, Malenović A. Robust Optimization of Chaotropic Chromatography Assay for Lamotrigine and its Two Impurities in Tablets. in Chromatographia. 2019;82(2):565-577.
doi:10.1007/s10337-018-3661-7 .

Colović, Jelena, Rmandić, Milena, Malenović, Anđelija, "Robust Optimization of Chaotropic Chromatography Assay for Lamotrigine and its Two Impurities in Tablets" in Chromatographia, 82, no. 2 (2019):565-577,
https://doi.org/10.1007/s10337-018-3661-7 . .

TY  - JOUR
AU  - Čolović, Jelena
AU  - Rmandić, Milena
AU  - Malenović, Anđelija
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3197
AB  - Numerous stationary phases have been developed with the aim to provide desired performances during chromatographic analysis of the basic solutes in their protonated form. In this work, the procedure for the characterization of bonded stationary phase performance, when both qualitative and quantitative chromatographic factors were varied in chaotropic chromatography, was proposed. Risperidone and its three impurities were selected as model substances, while acetonitrile content in the mobile phase (20-30%), the pH of the aqueous phase (3.00-5.00), the content of chaotropic agents in the aqueous phase (10-100 mM), type of chaotropic agent (NaClO4, CF3COONa), and stationary phase type (Zorbax Eclipse XDB, Zorbax Extend) were studied as chromatographic factors. The proposed procedure implies the combination of D-optimal experimental design, indirect modeling, and polynomial-modified Gaussian model, while grid point search method was selected for the final choice of the experimental conditions which lead to the best possible stationary phase performance for basic solutes. Good agreement between experimentally obtained chromatogram and simulated chromatogram for chosen experimental conditions (25% acetonitrile, 75 mM of NaClO4, pH 4.00 on Zorbax Eclipse XDB column) confirmed the applicability of the proposed procedure. The additional point was selected for the verification of proposed procedure ability to distinguish changes in solutes' elution order. Simulated chromatogram for 21.5% acetonitrile, 85 mM of NaClO4, pH 5.00 on Zorbax Eclipse XDB column was in line with experimental data. Furthermore, the values of left and right peak half-widths obtained from indirect modeling were used in order to evaluate performances of differently modified stationary phases applying a half-width plots approach. The results from half-width plot approach as well as from the proposed procedure indicate higher efficiency and better separation performance of the stationary phase extra densely bonded and double end-capped with trimethylsilyl group than the stationary phase with the combination of end-capping and bidentate silane bonding for chromatographic analysis of basic solutes in RP-HPLC systems with chaotropic agents.
PB  - Springer Heidelberg, Heidelberg
T2  - Analytical and Bioanalytical Chemistry
T1  - Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances
VL  - 410
IS  - 20
SP  - 4855
EP  - 4866
DO  - 10.1007/s00216-018-1122-7
ER  - 

@article{
author = "Čolović, Jelena and Rmandić, Milena and Malenović, Anđelija",
year = "2018",
abstract = "Numerous stationary phases have been developed with the aim to provide desired performances during chromatographic analysis of the basic solutes in their protonated form. In this work, the procedure for the characterization of bonded stationary phase performance, when both qualitative and quantitative chromatographic factors were varied in chaotropic chromatography, was proposed. Risperidone and its three impurities were selected as model substances, while acetonitrile content in the mobile phase (20-30%), the pH of the aqueous phase (3.00-5.00), the content of chaotropic agents in the aqueous phase (10-100 mM), type of chaotropic agent (NaClO4, CF3COONa), and stationary phase type (Zorbax Eclipse XDB, Zorbax Extend) were studied as chromatographic factors. The proposed procedure implies the combination of D-optimal experimental design, indirect modeling, and polynomial-modified Gaussian model, while grid point search method was selected for the final choice of the experimental conditions which lead to the best possible stationary phase performance for basic solutes. Good agreement between experimentally obtained chromatogram and simulated chromatogram for chosen experimental conditions (25% acetonitrile, 75 mM of NaClO4, pH 4.00 on Zorbax Eclipse XDB column) confirmed the applicability of the proposed procedure. The additional point was selected for the verification of proposed procedure ability to distinguish changes in solutes' elution order. Simulated chromatogram for 21.5% acetonitrile, 85 mM of NaClO4, pH 5.00 on Zorbax Eclipse XDB column was in line with experimental data. Furthermore, the values of left and right peak half-widths obtained from indirect modeling were used in order to evaluate performances of differently modified stationary phases applying a half-width plots approach. The results from half-width plot approach as well as from the proposed procedure indicate higher efficiency and better separation performance of the stationary phase extra densely bonded and double end-capped with trimethylsilyl group than the stationary phase with the combination of end-capping and bidentate silane bonding for chromatographic analysis of basic solutes in RP-HPLC systems with chaotropic agents.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Analytical and Bioanalytical Chemistry",
title = "Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances",
volume = "410",
number = "20",
pages = "4855-4866",
doi = "10.1007/s00216-018-1122-7"
}

Čolović, J., Rmandić, M.,& Malenović, A.. (2018). Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances. in Analytical and Bioanalytical Chemistry
Springer Heidelberg, Heidelberg., 410(20), 4855-4866.
https://doi.org/10.1007/s00216-018-1122-7

Čolović J, Rmandić M, Malenović A. Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances. in Analytical and Bioanalytical Chemistry. 2018;410(20):4855-4866.
doi:10.1007/s00216-018-1122-7 .

Čolović, Jelena, Rmandić, Milena, Malenović, Anđelija, "Characterization of bonded stationary phase performance as a function of qualitative and quantitative chromatographic factors in chaotropic chromatography with risperidone and its impurities as model substances" in Analytical and Bioanalytical Chemistry, 410, no. 20 (2018):4855-4866,
https://doi.org/10.1007/s00216-018-1122-7 . .

TY  - JOUR
AU  - Božić, Dragana
AU  - Pavlović, Bojan
AU  - Milovanović, Jovica
AU  - Jotić, Ana
AU  - Colović, Jelena
AU  - Cirković, Ivana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3212
AB  - Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). The aim of our study was to evaluate in vitro effects of amoxicillin-clavulanic acid and levofloxacin on biofilm formation by bacterial species isolated from sinus tissue in patients with CRSwNP. The sinus mucosal specimens were harvested from the upper parts and roof of ethmoid cavity of 48 patients with CRSwNP. Each sample was washed thoroughly in three separate beakers of sterile saline to remove any planktonic bacteria and further subjected to microbiology analysis. The biofilm-forming capacity of isolated strains was detected by microtiter-plate method and the effects of subinhibitory (1/2x to 1/16x MIC) and suprainhibitory concentrations (4, 8, 16, 32, and 64 A mu g/ml) of amoxicillin-clavulanic acid and levofloxacin on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one microorganism in 80.9% and two microorganisms in 19.1% of patients. The most prevalent bacteria in CRSwNP biofilms were Staphylococcus epidermidis (34%) and S. aureus (28%) followed by S. haemolyticus (12%), Pseudomonas aeruginosa (8%), Moraxella catarrhalis (6%), Streptococcus pneumoniae (6%), and other staphylococci (6%). Subinhibitory concentrations of amoxicillin-clavulanic acid and levofloxacin significantly reduced biofilm formation (p  lt  0.01 and p  lt  0.05, respectively), with better efficacy of amoxicillin-clavulanic acid (1/2-1/8x MIC) on staphylococci and levofloxacin (1/2- 1/4x MIC) on M. catarrhalis and P. aeruginosa biofilm formation. Suprainhibitory concentrations of both tested antibiotics (4-64 A mu g/ml) significantly eradicated mature biofilms of staphylococci (p  lt  0.01). The effect of levofloxacin on eradication of staphylococcal biofilms was more noticeable, compared to the effect of amoxicillin-clavulanic acid (p  lt  0.01). Suprainhibitory concentrations of both tested antibiotics had no effect on eradication of previously formed M. catarrhalis and P. aeruginosa biofilms (p > 0.05). The amoxicillin-clavulanic acid and levofloxacin are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and the volume of formed biofilm.
PB  - Springer, New York
T2  - European Archives of Oto-Rhino-Laryngology
T1  - Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients with chronic rhinosinusitis with nasal polyposis
VL  - 275
IS  - 8
SP  - 2051
EP  - 2059
DO  - 10.1007/s00405-018-5049-6
ER  - 

@article{
author = "Božić, Dragana and Pavlović, Bojan and Milovanović, Jovica and Jotić, Ana and Colović, Jelena and Cirković, Ivana",
year = "2018",
abstract = "Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). The aim of our study was to evaluate in vitro effects of amoxicillin-clavulanic acid and levofloxacin on biofilm formation by bacterial species isolated from sinus tissue in patients with CRSwNP. The sinus mucosal specimens were harvested from the upper parts and roof of ethmoid cavity of 48 patients with CRSwNP. Each sample was washed thoroughly in three separate beakers of sterile saline to remove any planktonic bacteria and further subjected to microbiology analysis. The biofilm-forming capacity of isolated strains was detected by microtiter-plate method and the effects of subinhibitory (1/2x to 1/16x MIC) and suprainhibitory concentrations (4, 8, 16, 32, and 64 A mu g/ml) of amoxicillin-clavulanic acid and levofloxacin on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one microorganism in 80.9% and two microorganisms in 19.1% of patients. The most prevalent bacteria in CRSwNP biofilms were Staphylococcus epidermidis (34%) and S. aureus (28%) followed by S. haemolyticus (12%), Pseudomonas aeruginosa (8%), Moraxella catarrhalis (6%), Streptococcus pneumoniae (6%), and other staphylococci (6%). Subinhibitory concentrations of amoxicillin-clavulanic acid and levofloxacin significantly reduced biofilm formation (p  lt  0.01 and p  lt  0.05, respectively), with better efficacy of amoxicillin-clavulanic acid (1/2-1/8x MIC) on staphylococci and levofloxacin (1/2- 1/4x MIC) on M. catarrhalis and P. aeruginosa biofilm formation. Suprainhibitory concentrations of both tested antibiotics (4-64 A mu g/ml) significantly eradicated mature biofilms of staphylococci (p  lt  0.01). The effect of levofloxacin on eradication of staphylococcal biofilms was more noticeable, compared to the effect of amoxicillin-clavulanic acid (p  lt  0.01). Suprainhibitory concentrations of both tested antibiotics had no effect on eradication of previously formed M. catarrhalis and P. aeruginosa biofilms (p > 0.05). The amoxicillin-clavulanic acid and levofloxacin are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and the volume of formed biofilm.",
publisher = "Springer, New York",
journal = "European Archives of Oto-Rhino-Laryngology",
title = "Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients with chronic rhinosinusitis with nasal polyposis",
volume = "275",
number = "8",
pages = "2051-2059",
doi = "10.1007/s00405-018-5049-6"
}

Božić, D., Pavlović, B., Milovanović, J., Jotić, A., Colović, J.,& Cirković, I.. (2018). Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients with chronic rhinosinusitis with nasal polyposis. in European Archives of Oto-Rhino-Laryngology
Springer, New York., 275(8), 2051-2059.
https://doi.org/10.1007/s00405-018-5049-6

Božić D, Pavlović B, Milovanović J, Jotić A, Colović J, Cirković I. Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients with chronic rhinosinusitis with nasal polyposis. in European Archives of Oto-Rhino-Laryngology. 2018;275(8):2051-2059.
doi:10.1007/s00405-018-5049-6 .

Božić, Dragana, Pavlović, Bojan, Milovanović, Jovica, Jotić, Ana, Colović, Jelena, Cirković, Ivana, "Antibiofilm effects of amoxicillin-clavulanic acid and levofloxacin in patients with chronic rhinosinusitis with nasal polyposis" in European Archives of Oto-Rhino-Laryngology, 275, no. 8 (2018):2051-2059,
https://doi.org/10.1007/s00405-018-5049-6 . .

TY  - CHAP
AU  - Vemić, Ana
AU  - Kalinić, Marko
AU  - Čolović, Jelena
AU  - Erić, Slavica
AU  - Malenović, Anđelija
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3235
PB  - CRC Press-Taylor and Francis Group
T2  - Advances in Chromatography, Vol 54
T1  - Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications
VL  - 54
SP  - 1
EP  - 41
UR  - https://hdl.handle.net/21.15107/rcub_farfar_3235
ER  - 

@inbook{
author = "Vemić, Ana and Kalinić, Marko and Čolović, Jelena and Erić, Slavica and Malenović, Anđelija",
year = "2018",
publisher = "CRC Press-Taylor and Francis Group",
journal = "Advances in Chromatography, Vol 54",
booktitle = "Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications",
volume = "54",
pages = "1-41",
url = "https://hdl.handle.net/21.15107/rcub_farfar_3235"
}

Vemić, A., Kalinić, M., Čolović, J., Erić, S.,& Malenović, A.. (2018). Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications. in Advances in Chromatography, Vol 54
CRC Press-Taylor and Francis Group., 54, 1-41.
https://hdl.handle.net/21.15107/rcub_farfar_3235

Vemić A, Kalinić M, Čolović J, Erić S, Malenović A. Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications. in Advances in Chromatography, Vol 54. 2018;54:1-41.
https://hdl.handle.net/21.15107/rcub_farfar_3235 .

Vemić, Ana, Kalinić, Marko, Čolović, Jelena, Erić, Slavica, Malenović, Anđelija, "Recent Progress in Fundamental Understanding and Practice of Chaotropic Chromatography Rationalizing the Effects of Analytes' Structure with Pharmaceutical Applications" in Advances in Chromatography, Vol 54, 54 (2018):1-41,
https://hdl.handle.net/21.15107/rcub_farfar_3235 .

TY  - JOUR
AU  - Colović, Jelena
AU  - Kalinić, Marko
AU  - Vemić, Ana
AU  - Erić, Slavica
AU  - Malenović, Anđelija
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2807
AB  - In this study, we present novel insights into the pH-dependent retention behavior of protonated basic solutes in chaotropic chromatography. To this end, two sets of experiments were performed to distinguish between mobile phase pH and ionic strength effects. In the first set, the ionic strength (I) was varied with the concentration of NaPF6 and additives that adjusted the mobile phase pH, while in the second set, I was kept constant by adding the appropriate amount of NaCl. In each set, the retention behavior of 13 analytes was qualitatively examined in 21 chromatographic systems, which were defined by the NaPF6 concentration in their aqueous phases (1-50 mM) and the pH of their mobile phases (2,3 or 4); the acetonitrile content was fixed at 40%. The addition of NaCl significantly reduced the differences among retention factors at studied pH values due to the effect of the Na+ ions on PF6- adsorption to the stationary phase and the magnitude of the consequential development of the surface potential. A quantitative description of the observed phenomenon was obtained by an extended thermodynamic approach. The contribution of ion-pair formation in the stationary phase to the retention of the solutes was confirmed across models at the studied pH values in the set with varying I In the systems with a constant I, the shielding effect of the Na+ ions on the surface charge lowered the attractive surface potential and diminished the aforementioned interactions and hence the effect of the mobile phase pH on analyte retention. Eventually, we developed a readily interpretable empirical retention model that simultaneously takes into account analyte molecular structures and the most relevant chromatographic factors. Its coefficients have clear physical meaning, and owing to its good predictive capabilities, the model could be successfully used to clarify the contributions of analyte molecular structures and chromatographic factors to the specific processes underlying separation in chaotropic chromatography.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography
VL  - 1511
SP  - 68
EP  - 76
DO  - 10.1016/j.chroma.2017.06.069
ER  - 

@article{
author = "Colović, Jelena and Kalinić, Marko and Vemić, Ana and Erić, Slavica and Malenović, Anđelija",
year = "2017",
abstract = "In this study, we present novel insights into the pH-dependent retention behavior of protonated basic solutes in chaotropic chromatography. To this end, two sets of experiments were performed to distinguish between mobile phase pH and ionic strength effects. In the first set, the ionic strength (I) was varied with the concentration of NaPF6 and additives that adjusted the mobile phase pH, while in the second set, I was kept constant by adding the appropriate amount of NaCl. In each set, the retention behavior of 13 analytes was qualitatively examined in 21 chromatographic systems, which were defined by the NaPF6 concentration in their aqueous phases (1-50 mM) and the pH of their mobile phases (2,3 or 4); the acetonitrile content was fixed at 40%. The addition of NaCl significantly reduced the differences among retention factors at studied pH values due to the effect of the Na+ ions on PF6- adsorption to the stationary phase and the magnitude of the consequential development of the surface potential. A quantitative description of the observed phenomenon was obtained by an extended thermodynamic approach. The contribution of ion-pair formation in the stationary phase to the retention of the solutes was confirmed across models at the studied pH values in the set with varying I In the systems with a constant I, the shielding effect of the Na+ ions on the surface charge lowered the attractive surface potential and diminished the aforementioned interactions and hence the effect of the mobile phase pH on analyte retention. Eventually, we developed a readily interpretable empirical retention model that simultaneously takes into account analyte molecular structures and the most relevant chromatographic factors. Its coefficients have clear physical meaning, and owing to its good predictive capabilities, the model could be successfully used to clarify the contributions of analyte molecular structures and chromatographic factors to the specific processes underlying separation in chaotropic chromatography.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography",
volume = "1511",
pages = "68-76",
doi = "10.1016/j.chroma.2017.06.069"
}

Colović, J., Kalinić, M., Vemić, A., Erić, S.,& Malenović, A.. (2017). Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1511, 68-76.
https://doi.org/10.1016/j.chroma.2017.06.069

Colović J, Kalinić M, Vemić A, Erić S, Malenović A. Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography. in Journal of Chromatography A. 2017;1511:68-76.
doi:10.1016/j.chroma.2017.06.069 .

Colović, Jelena, Kalinić, Marko, Vemić, Ana, Erić, Slavica, Malenović, Anđelija, "Influence of the mobile phase and molecular structure parameters on the retention behavior of protonated basic solutes in chaotropic chromatography" in Journal of Chromatography A, 1511 (2017):68-76,
https://doi.org/10.1016/j.chroma.2017.06.069 . .

TY  - JOUR
AU  - Milošević, Nenad
AU  - Vemić, Ana
AU  - Colović, Jelena
AU  - Kostić, Nada
AU  - Malenović, Anđelija
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3004
AB  - The quality by design approach has been applied to develop a chaotropic chromatography method for determination of trimetazidine dihydrochloride (TMZ) and two impurities (Y-145, Y-234). Baseline separation and accurate determination of the investigated analytes was set as the target analytical profile, with k (Y-145), k (TMZ), and alpha (Y-145/TMZ) selected as critical quality attributes. The critical process parameters studied in this research were pH of water phase, acetonitrile content in mobile phase, and concentration of perchloric acid in water phase. To compute a design space as a region of the knowledge space having satisfactory values of all critical quality attributes at the desired quality level, Monte Carlo simulations were performed to propagate the error originating from the calculated model coefficients to the predicted responses. At each of 4851 defined grid points, 5000 iterations were performed and the region having probability pi ae lt yen> 95% of achieving all defined critical quality attributes was computed. A working point situated in the center of the design space was chosen, corresponding to 27% acetonitrile in mobile phase, 63% 170 mM perchloric acid in water phase, and pH of water phase adjusted to 3.60. The method was validated to confirm its reliability for use in routine pharmaceutical analysis.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Design of Experiments-Design Space Approach for Development of Chaotropic Chromatography Method for Determination of Trimetazidine Dihydrochloride and Two Impurities
VL  - 80
IS  - 4
SP  - 585
EP  - 592
DO  - 10.1007/s10337-017-3275-5
ER  - 

@article{
author = "Milošević, Nenad and Vemić, Ana and Colović, Jelena and Kostić, Nada and Malenović, Anđelija",
year = "2017",
abstract = "The quality by design approach has been applied to develop a chaotropic chromatography method for determination of trimetazidine dihydrochloride (TMZ) and two impurities (Y-145, Y-234). Baseline separation and accurate determination of the investigated analytes was set as the target analytical profile, with k (Y-145), k (TMZ), and alpha (Y-145/TMZ) selected as critical quality attributes. The critical process parameters studied in this research were pH of water phase, acetonitrile content in mobile phase, and concentration of perchloric acid in water phase. To compute a design space as a region of the knowledge space having satisfactory values of all critical quality attributes at the desired quality level, Monte Carlo simulations were performed to propagate the error originating from the calculated model coefficients to the predicted responses. At each of 4851 defined grid points, 5000 iterations were performed and the region having probability pi ae lt yen> 95% of achieving all defined critical quality attributes was computed. A working point situated in the center of the design space was chosen, corresponding to 27% acetonitrile in mobile phase, 63% 170 mM perchloric acid in water phase, and pH of water phase adjusted to 3.60. The method was validated to confirm its reliability for use in routine pharmaceutical analysis.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Design of Experiments-Design Space Approach for Development of Chaotropic Chromatography Method for Determination of Trimetazidine Dihydrochloride and Two Impurities",
volume = "80",
number = "4",
pages = "585-592",
doi = "10.1007/s10337-017-3275-5"
}

Milošević, N., Vemić, A., Colović, J., Kostić, N.,& Malenović, A.. (2017). Design of Experiments-Design Space Approach for Development of Chaotropic Chromatography Method for Determination of Trimetazidine Dihydrochloride and Two Impurities. in Chromatographia
Springer Heidelberg, Heidelberg., 80(4), 585-592.
https://doi.org/10.1007/s10337-017-3275-5

Milošević N, Vemić A, Colović J, Kostić N, Malenović A. Design of Experiments-Design Space Approach for Development of Chaotropic Chromatography Method for Determination of Trimetazidine Dihydrochloride and Two Impurities. in Chromatographia. 2017;80(4):585-592.
doi:10.1007/s10337-017-3275-5 .

Milošević, Nenad, Vemić, Ana, Colović, Jelena, Kostić, Nada, Malenović, Anđelija, "Design of Experiments-Design Space Approach for Development of Chaotropic Chromatography Method for Determination of Trimetazidine Dihydrochloride and Two Impurities" in Chromatographia, 80, no. 4 (2017):585-592,
https://doi.org/10.1007/s10337-017-3275-5 . .

TY  - JOUR
AU  - Colović, Jelena
AU  - Kalinić, Marko
AU  - Vemić, Ana
AU  - Erić, Slavica
AU  - Malenović, Anđelija
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2365
AB  - The aim of this study was to systematically investigate the phenomena affecting the retention behavior of structurally diverse basic drugs in ion-interaction chromatographic systems with chaotropic additives. To this end, the influence of three factors was studied: pH value of the aqueous phase, concentration of sodium hexafluorophosphate, and content of acetonitrile in the mobile phase. Mobile phase pH was found to affect the thermodynamic equilibria in the studied system beyond its effects on the analytes' ionization state. Specifically, increasing pH from 2 to 4 led to longer retention times, even with analytes which remain completely protonated. An explanation for this phenomenon was sought by studying the adsorption behavior of acetonitrile and chaotropic additive onto stationary phase. It was shown that the magnitude of the developed surface potential, which significantly affects retention - increases with pH, and that this can be attributed to the larger surface excess of acetonitrile. To study how analytes' structural properties influence their retention, quantitative structure-retention modeling was performed next. A support vector machine regression model was developed, relating mobile phase constituents and structural descriptors with retention data. While the ETA_EtaP_B_RC and XlogP can be considered as molecular descriptors which describe factors affecting retention in any RP-HPLC system, TDB9p and RDF45p are molecular descriptors which account for spatial arrangement of polarizable atoms and they can clearly relate to analytes' behavior on the stationary phase surface, where the electrostatic potential develops. Complementarity of analytes' structure with that of the electric double layer can be seen as a key factor influencing their retention behavior. Structural diversity of analytes and good predictive capabilities over a range of experimental conditions make the established model a useful tool in predicting retention behavior in the studied chromatographic system.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties
VL  - 1425
SP  - 150
EP  - 157
DO  - 10.1016/j.chroma.2015.11.027
ER  - 

@article{
author = "Colović, Jelena and Kalinić, Marko and Vemić, Ana and Erić, Slavica and Malenović, Anđelija",
year = "2015",
abstract = "The aim of this study was to systematically investigate the phenomena affecting the retention behavior of structurally diverse basic drugs in ion-interaction chromatographic systems with chaotropic additives. To this end, the influence of three factors was studied: pH value of the aqueous phase, concentration of sodium hexafluorophosphate, and content of acetonitrile in the mobile phase. Mobile phase pH was found to affect the thermodynamic equilibria in the studied system beyond its effects on the analytes' ionization state. Specifically, increasing pH from 2 to 4 led to longer retention times, even with analytes which remain completely protonated. An explanation for this phenomenon was sought by studying the adsorption behavior of acetonitrile and chaotropic additive onto stationary phase. It was shown that the magnitude of the developed surface potential, which significantly affects retention - increases with pH, and that this can be attributed to the larger surface excess of acetonitrile. To study how analytes' structural properties influence their retention, quantitative structure-retention modeling was performed next. A support vector machine regression model was developed, relating mobile phase constituents and structural descriptors with retention data. While the ETA_EtaP_B_RC and XlogP can be considered as molecular descriptors which describe factors affecting retention in any RP-HPLC system, TDB9p and RDF45p are molecular descriptors which account for spatial arrangement of polarizable atoms and they can clearly relate to analytes' behavior on the stationary phase surface, where the electrostatic potential develops. Complementarity of analytes' structure with that of the electric double layer can be seen as a key factor influencing their retention behavior. Structural diversity of analytes and good predictive capabilities over a range of experimental conditions make the established model a useful tool in predicting retention behavior in the studied chromatographic system.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties",
volume = "1425",
pages = "150-157",
doi = "10.1016/j.chroma.2015.11.027"
}

Colović, J., Kalinić, M., Vemić, A., Erić, S.,& Malenović, A.. (2015). Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1425, 150-157.
https://doi.org/10.1016/j.chroma.2015.11.027

Colović J, Kalinić M, Vemić A, Erić S, Malenović A. Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties. in Journal of Chromatography A. 2015;1425:150-157.
doi:10.1016/j.chroma.2015.11.027 .

Colović, Jelena, Kalinić, Marko, Vemić, Ana, Erić, Slavica, Malenović, Anđelija, "Investigation into the phenomena affecting the retention behavior of basic analytes in chaotropic chromatography: Joint effects of the most relevant chromatographic factors and analytes' molecular properties" in Journal of Chromatography A, 1425 (2015):150-157,
https://doi.org/10.1016/j.chroma.2015.11.027 . .

TY  - JOUR
AU  - Colović, Jelena
AU  - Vemić, Ana
AU  - Kostić, Nada
AU  - Malenović, Anđelija
AU  - Medenica, Mirjana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2092
AB  - In this paper, the capability of a polynomial-modified Gaussian model to relate the peak shape of basic analytes, amlodipine, and its impurity A, with the change of chromatographic conditions was tested. For the accurate simulation of real chromatographic peaks the authors proposed the three-step procedure based on indirect modeling of peak width at 10% of peak height (W-0.1), individual values of left-half width (A) and right-half width (B), number of theoretical plates (N), and tailing factor (Tf). The values of retention factors corresponding to the peak beginning (k(B)), peak apex (k(A)), peak ending (k(E)), and peak heights (H-0) of the analytes were directly modeled. Then, the investigated experimental domain was divided to acquire a grid of appropriate density, which allowed the subsequent calculation of W-0.1, A, B, N, and Tf. On the basis of the predicted results for Tf and N, as well as the defined criteria for the simulation the following conditions were selected: 33% acetonitrile/67% aqueous phase (55 mM perchloric acid, pH 2.2) at 40 degrees C column temperature. Perfect agreement between predicted and experimental values was obtained confirming the ability of polynomial modified Gaussian model and three-step procedure to successfully simulate the real chromatograms in ion-interaction chromatography.
PB  - Wiley-VCH Verlag GMBH, Weinheim
T2  - Journal of Separation Science
T1  - Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography
VL  - 37
IS  - 14
SP  - 1797
EP  - 1804
DO  - 10.1002/jssc.201400206
ER  - 

@article{
author = "Colović, Jelena and Vemić, Ana and Kostić, Nada and Malenović, Anđelija and Medenica, Mirjana",
year = "2014",
abstract = "In this paper, the capability of a polynomial-modified Gaussian model to relate the peak shape of basic analytes, amlodipine, and its impurity A, with the change of chromatographic conditions was tested. For the accurate simulation of real chromatographic peaks the authors proposed the three-step procedure based on indirect modeling of peak width at 10% of peak height (W-0.1), individual values of left-half width (A) and right-half width (B), number of theoretical plates (N), and tailing factor (Tf). The values of retention factors corresponding to the peak beginning (k(B)), peak apex (k(A)), peak ending (k(E)), and peak heights (H-0) of the analytes were directly modeled. Then, the investigated experimental domain was divided to acquire a grid of appropriate density, which allowed the subsequent calculation of W-0.1, A, B, N, and Tf. On the basis of the predicted results for Tf and N, as well as the defined criteria for the simulation the following conditions were selected: 33% acetonitrile/67% aqueous phase (55 mM perchloric acid, pH 2.2) at 40 degrees C column temperature. Perfect agreement between predicted and experimental values was obtained confirming the ability of polynomial modified Gaussian model and three-step procedure to successfully simulate the real chromatograms in ion-interaction chromatography.",
publisher = "Wiley-VCH Verlag GMBH, Weinheim",
journal = "Journal of Separation Science",
title = "Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography",
volume = "37",
number = "14",
pages = "1797-1804",
doi = "10.1002/jssc.201400206"
}

Colović, J., Vemić, A., Kostić, N., Malenović, A.,& Medenica, M.. (2014). Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography. in Journal of Separation Science
Wiley-VCH Verlag GMBH, Weinheim., 37(14), 1797-1804.
https://doi.org/10.1002/jssc.201400206

Colović J, Vemić A, Kostić N, Malenović A, Medenica M. Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography. in Journal of Separation Science. 2014;37(14):1797-1804.
doi:10.1002/jssc.201400206 .

Colović, Jelena, Vemić, Ana, Kostić, Nada, Malenović, Anđelija, Medenica, Mirjana, "Testing the capability of a polynomial-modified gaussian model in the description and simulation of chromatographic peaks of amlodipine and its impurity in ion-interaction chromatography" in Journal of Separation Science, 37, no. 14 (2014):1797-1804,
https://doi.org/10.1002/jssc.201400206 . .