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  - Foivas, Anargyros
AU  - Malenović, Anđelija
AU  - Kostić, Nada
AU  - Božić, Marija
AU  - Knežević, Miroslav
AU  - Loukas, Yannis L.
AU  - Dotsikas, Yannis
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2566
AB  - In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10 mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350 mL/min yielding retention times of 1.7 min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0 mu g/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 922 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method
VL  - 119
SP  - 84
EP  - 90
DO  - 10.1016/j.jpba.2015.11.043
ER  - 

@article{
author = "Foivas, Anargyros and Malenović, Anđelija and Kostić, Nada and Božić, Marija and Knežević, Miroslav and Loukas, Yannis L. and Dotsikas, Yannis",
year = "2016",
abstract = "In the current study, a rapid and sensitive LC-QTOF-MS/MS method for the determination of brinzolamide in dried blood spots (DBS) was developed and validated. This novel sample collection, storage and transfer technique was suitable for analyzing a drug with high distribution into red blood cells and negligible plasma levels. The method included an isocratic mobile phase consisting of methanol and 10 mM ammonium formate (90:10, v/v) and detection in positive electrospray mode (ESI+). The flow rate was adjusted to 0.350 mL/min yielding retention times of 1.7 min for both brinzolamide and internal standard (IS) rabeprazole on a Cyano analytical column, respectively. The validation of the proposed method over the concentration range 0.500-20.0 mu g/mL was performed in compliance with EMEA and FDA guidelines, assessing all major performance characteristics. Inter- and intra- assay precisions were less than 14%, while inter- and intra- assay accuracies varied from 922 to 111%. No matrix effect was observed and the mean brinzolamide extraction recovery was 93.5%. The method was successfully applied to real DBS samples from patients in steady state condition, receiving brinzolamide ophthalmic suspension 1% (w/v) for several months. Initial concentrations were corrected due to hematocrit effect, using image processing algorithm written in Matlab.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method",
volume = "119",
pages = "84-90",
doi = "10.1016/j.jpba.2015.11.043"
}

Foivas, A., Malenović, A., Kostić, N., Božić, M., Knežević, M., Loukas, Y. L.,& Dotsikas, Y.. (2016). Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 119, 84-90.
https://doi.org/10.1016/j.jpba.2015.11.043

Foivas A, Malenović A, Kostić N, Božić M, Knežević M, Loukas YL, Dotsikas Y. Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method. in Journal of Pharmaceutical and Biomedical Analysis. 2016;119:84-90.
doi:10.1016/j.jpba.2015.11.043 .

Foivas, Anargyros, Malenović, Anđelija, Kostić, Nada, Božić, Marija, Knežević, Miroslav, Loukas, Yannis L., Dotsikas, Yannis, "Quantitation of brinzolamide in dried blood spots by a novel LC-QTOF-MS/MS method" in Journal of Pharmaceutical and Biomedical Analysis, 119 (2016):84-90,
https://doi.org/10.1016/j.jpba.2015.11.043 . .

TY  - JOUR
AU  - Pantović, Jasmina
AU  - Malenović, Anđelija
AU  - Vemić, Ana
AU  - Kostić, Nada
AU  - Medenica, Mirjana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2454
AB  - In this paper, the development of reversed-phase liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality by design (QbD) approach is presented. The defined analytical target profile (ATP) was the efficient baseline separation and the accurate determination of the investigated analytes. The selected critical quality attributes (CQAs) were the separation criterions between the critical peak pairs because the mixture complexity imposed a gradient elution mode. The critical process parameters (CPPs) studied in this research were acetonitrile content at the beginning of gradient program, acetonitrile content at the end of gradient program and the gradient time. Plan of experiments was defined by Box-Behnken design. The experimental domains of the three selected factors x1 - content of the acetonitrile at the start of linear gradient, x2 - content of the acetonitrile at the end of linear gradient and x3 - gradient time (t(G)) were 110%, 30%], [48%, 60%] and [8 min, 15 min], respectively. In order to define the design space (DS) as a zone where the desired quality criteria is met providing also the quality assurance, Monte Carlo simulations were performed. The uniform error distribution equal to the calculated standard error was added to the model coefficient estimates. Monte Carlo simulation included 5000 iterations in each of 3969 defined grid points and the region having the probability pi >= 95% to achieve satisfactory values of all defined CQAs was computed. As a working point, following chromatographic conditions suited in the middle of the DS were chosen: 22% acetonitrile at the start of gradient program, 55.5% acetonitrile at the end of gradient program end and the gradient time of 11.5 min. The developed method was validated in order to prove its reliability.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology
VL  - 111
SP  - 7
EP  - 13
DO  - 10.1016/j.jpba.2015.03.009
ER  - 

@article{
author = "Pantović, Jasmina and Malenović, Anđelija and Vemić, Ana and Kostić, Nada and Medenica, Mirjana",
year = "2015",
abstract = "In this paper, the development of reversed-phase liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality by design (QbD) approach is presented. The defined analytical target profile (ATP) was the efficient baseline separation and the accurate determination of the investigated analytes. The selected critical quality attributes (CQAs) were the separation criterions between the critical peak pairs because the mixture complexity imposed a gradient elution mode. The critical process parameters (CPPs) studied in this research were acetonitrile content at the beginning of gradient program, acetonitrile content at the end of gradient program and the gradient time. Plan of experiments was defined by Box-Behnken design. The experimental domains of the three selected factors x1 - content of the acetonitrile at the start of linear gradient, x2 - content of the acetonitrile at the end of linear gradient and x3 - gradient time (t(G)) were 110%, 30%], [48%, 60%] and [8 min, 15 min], respectively. In order to define the design space (DS) as a zone where the desired quality criteria is met providing also the quality assurance, Monte Carlo simulations were performed. The uniform error distribution equal to the calculated standard error was added to the model coefficient estimates. Monte Carlo simulation included 5000 iterations in each of 3969 defined grid points and the region having the probability pi >= 95% to achieve satisfactory values of all defined CQAs was computed. As a working point, following chromatographic conditions suited in the middle of the DS were chosen: 22% acetonitrile at the start of gradient program, 55.5% acetonitrile at the end of gradient program end and the gradient time of 11.5 min. The developed method was validated in order to prove its reliability.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology",
volume = "111",
pages = "7-13",
doi = "10.1016/j.jpba.2015.03.009"
}

Pantović, J., Malenović, A., Vemić, A., Kostić, N.,& Medenica, M.. (2015). Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 111, 7-13.
https://doi.org/10.1016/j.jpba.2015.03.009

Pantović J, Malenović A, Vemić A, Kostić N, Medenica M. Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology. in Journal of Pharmaceutical and Biomedical Analysis. 2015;111:7-13.
doi:10.1016/j.jpba.2015.03.009 .

Pantović, Jasmina, Malenović, Anđelija, Vemić, Ana, Kostić, Nada, Medenica, Mirjana, "Development of liquid chromatographic method for the analysis of dabigatran etexilate mesilate and its ten impurities supported by quality-by-design methodology" in Journal of Pharmaceutical and Biomedical Analysis, 111 (2015):7-13,
https://doi.org/10.1016/j.jpba.2015.03.009 . .

TY  - JOUR
AU  - Kostić, Nada
AU  - Dotsikas, Yannis
AU  - Jović, Nebojša
AU  - Stevanović, Galina
AU  - Malenović, Anđelija
AU  - Medenica, Mirjana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2410
AB  - In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50 mm x 4.0 mm, 3 mu m particle size) maintained at 30 degrees C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550 mu L/min and total run time 2 min. Established methods were fully validated over the concentration range of 0.200-20.0 mu g/mL for DBS and 0.400-40.0 mu g/mL for DPS, respectively, while specificity, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods
VL  - 109
SP  - 79
EP  - 84
DO  - 10.1016/j.jpba.2015.02.023
ER  - 

@article{
author = "Kostić, Nada and Dotsikas, Yannis and Jović, Nebojša and Stevanović, Galina and Malenović, Anđelija and Medenica, Mirjana",
year = "2015",
abstract = "In this paper, novel LC-MS/MS methods for the determination of antiepileptic drug pregabalin in dried matrix spots (DMS) are presented. This attractive technique of sample collection in micro amount was utilized in the form of dried blood spots (DBS) and dried plasma spots (DPS). Following a pre-column derivatization procedure, using n-propyl chloroformate in the presence of n-propanol, and consecutive liquid-liquid extraction, derivatized pregabalin and its internal standard, 4-aminocyclohexanecarboxylic acid, were detected in positive ion mode by applying two SRM transitions per analyte. A YMC-Pack Octyl column (50 mm x 4.0 mm, 3 mu m particle size) maintained at 30 degrees C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550 mu L/min and total run time 2 min. Established methods were fully validated over the concentration range of 0.200-20.0 mu g/mL for DBS and 0.400-40.0 mu g/mL for DPS, respectively, while specificity, accuracy, precision, recovery, matrix-effect, stability, dilution integrity and spot homogeneity were found within acceptance criteria. Validated methods were applied for the determination of pregabalin levels in dried blood and plasma samples obtained from patients with epilepsy, after per os administration of commercial capsules. Comparison of drug level in blood and plasma, as well as correction steps undertaken in order to overcome hematocrit issue, when analyzing DBS, are also given.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods",
volume = "109",
pages = "79-84",
doi = "10.1016/j.jpba.2015.02.023"
}

Kostić, N., Dotsikas, Y., Jović, N., Stevanović, G., Malenović, A.,& Medenica, M.. (2015). Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 109, 79-84.
https://doi.org/10.1016/j.jpba.2015.02.023

Kostić N, Dotsikas Y, Jović N, Stevanović G, Malenović A, Medenica M. Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods. in Journal of Pharmaceutical and Biomedical Analysis. 2015;109:79-84.
doi:10.1016/j.jpba.2015.02.023 .

Kostić, Nada, Dotsikas, Yannis, Jović, Nebojša, Stevanović, Galina, Malenović, Anđelija, Medenica, Mirjana, "Quantitation of pregabalin in dried blood spots and dried plasma spots by validated LC-MS/MS methods" in Journal of Pharmaceutical and Biomedical Analysis, 109 (2015):79-84,
https://doi.org/10.1016/j.jpba.2015.02.023 . .

TY  - JOUR
AU  - Kostić, Nada
AU  - Dotsikas, Yannis
AU  - Malenović, Anđelija
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2228
AB  - Drugs with antiepileptic activity constitute a group of heterogeneous compounds and therefore their determination cannot follow a universal procedure. Among them, vigabatrin, pregabalin, and gabapentin are of similar nature, due to their zwitterionic structure. This structure enables similar approaches for their determination, including derivatization protocols. This article presents a thorough survey on published methods for the determination of this subgroup of antiepileptic compounds in bulk and pharmaceutical preparations. Spectrophotometric and spectrofluorimetric methods, with or without derivatization reagents, as thin-layer chromatography, high-performance liquid chromatography with various detectors, gas chromatography, capillary electrophoresis, infrared, and potentiometric methods, have been extensively applied for these compounds, providing reliable results. Additionally, the number of citations and purpose for each method were discussed with critical commentary.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Instrumentation Science & Technology
T1  - Critical review on the analytical methods for the determination of zwitterionic antiepileptic drugs-Vigabatrin, Pregabalin, and Gabapentin - In bulk and formulations
VL  - 42
IS  - 4
SP  - 486
EP  - 512
DO  - 10.1080/10739149.2013.876545
ER  - 

@article{
author = "Kostić, Nada and Dotsikas, Yannis and Malenović, Anđelija",
year = "2014",
abstract = "Drugs with antiepileptic activity constitute a group of heterogeneous compounds and therefore their determination cannot follow a universal procedure. Among them, vigabatrin, pregabalin, and gabapentin are of similar nature, due to their zwitterionic structure. This structure enables similar approaches for their determination, including derivatization protocols. This article presents a thorough survey on published methods for the determination of this subgroup of antiepileptic compounds in bulk and pharmaceutical preparations. Spectrophotometric and spectrofluorimetric methods, with or without derivatization reagents, as thin-layer chromatography, high-performance liquid chromatography with various detectors, gas chromatography, capillary electrophoresis, infrared, and potentiometric methods, have been extensively applied for these compounds, providing reliable results. Additionally, the number of citations and purpose for each method were discussed with critical commentary.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Instrumentation Science & Technology",
title = "Critical review on the analytical methods for the determination of zwitterionic antiepileptic drugs-Vigabatrin, Pregabalin, and Gabapentin - In bulk and formulations",
volume = "42",
number = "4",
pages = "486-512",
doi = "10.1080/10739149.2013.876545"
}

Kostić, N., Dotsikas, Y.,& Malenović, A.. (2014). Critical review on the analytical methods for the determination of zwitterionic antiepileptic drugs-Vigabatrin, Pregabalin, and Gabapentin - In bulk and formulations. in Instrumentation Science & Technology
Taylor & Francis Inc, Philadelphia., 42(4), 486-512.
https://doi.org/10.1080/10739149.2013.876545

Kostić N, Dotsikas Y, Malenović A. Critical review on the analytical methods for the determination of zwitterionic antiepileptic drugs-Vigabatrin, Pregabalin, and Gabapentin - In bulk and formulations. in Instrumentation Science & Technology. 2014;42(4):486-512.
doi:10.1080/10739149.2013.876545 .

Kostić, Nada, Dotsikas, Yannis, Malenović, Anđelija, "Critical review on the analytical methods for the determination of zwitterionic antiepileptic drugs-Vigabatrin, Pregabalin, and Gabapentin - In bulk and formulations" in Instrumentation Science & Technology, 42, no. 4 (2014):486-512,
https://doi.org/10.1080/10739149.2013.876545 . .

TY  - JOUR
AU  - Kostić, Nada
AU  - Dotsikas, Yannis
AU  - Jović, Nebojša
AU  - Stevanović, Galina
AU  - Malenović, Anđelija
AU  - Medenica, Mirjana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2212
AB  - This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time. A relatively novel sample collection technique, DPS, was utilized, offering easy sample handling and analysis, using a sample in micro amount (similar to 5 mu L). Derivatized vigabatrin and its internal standard, 4-aminocyclohexanecarboxylic acid, were extracted by liquid-liquid extraction (LLE) and determined in positive ion mode by applying two SRM transitions per analyte. A Zorbax Eclipse XDB-C8 column (150 x 4.6 mm, 5 mu m particle size) maintained at 30 degrees C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550 mu L/min and total run time 4.5 min. The assay exhibited excellent linearity over the concentration range of 0.500-50.0 mu g/mL, which is suitable for the determination of vigabatrin level after per os administration in children and youths with epilepsy, who were on vigabatrin therapy, with or without co-medication. Specificity, accuracy, precision, recovery, matrix-effect and stability were also estimated and assessed within acceptance criteria.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences
T1  - Vigabatrin in dried plasma spots: Validation of a novel LC-MS/MS method and application to clinical practice
VL  - 962
SP  - 102
EP  - 108
DO  - 10.1016/j.jchromb.2014.05.037
ER  - 

@article{
author = "Kostić, Nada and Dotsikas, Yannis and Jović, Nebojša and Stevanović, Galina and Malenović, Anđelija and Medenica, Mirjana",
year = "2014",
abstract = "This paper presents a LC-MS/MS method for the determination of antiepileptic drug vigabatrin in dried plasma spots (DPS). Due to its zwitterionic chemical structure, a pre-column derivatization procedure was performed, aiming to yield enhanced ionization efficiency and improved chromatographic behaviour. Propyl chloroformate, in the presence of propanol, was selected as the best derivatization reagent, providing a strong signal along with reasonable run time. A relatively novel sample collection technique, DPS, was utilized, offering easy sample handling and analysis, using a sample in micro amount (similar to 5 mu L). Derivatized vigabatrin and its internal standard, 4-aminocyclohexanecarboxylic acid, were extracted by liquid-liquid extraction (LLE) and determined in positive ion mode by applying two SRM transitions per analyte. A Zorbax Eclipse XDB-C8 column (150 x 4.6 mm, 5 mu m particle size) maintained at 30 degrees C, was utilized with running mobile phase composed of acetonitrile: 0.15% formic acid (85:15, v/v). Flow rate was 550 mu L/min and total run time 4.5 min. The assay exhibited excellent linearity over the concentration range of 0.500-50.0 mu g/mL, which is suitable for the determination of vigabatrin level after per os administration in children and youths with epilepsy, who were on vigabatrin therapy, with or without co-medication. Specificity, accuracy, precision, recovery, matrix-effect and stability were also estimated and assessed within acceptance criteria.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences",
title = "Vigabatrin in dried plasma spots: Validation of a novel LC-MS/MS method and application to clinical practice",
volume = "962",
pages = "102-108",
doi = "10.1016/j.jchromb.2014.05.037"
}

Kostić, N., Dotsikas, Y., Jović, N., Stevanović, G., Malenović, A.,& Medenica, M.. (2014). Vigabatrin in dried plasma spots: Validation of a novel LC-MS/MS method and application to clinical practice. in Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences
Elsevier Science BV, Amsterdam., 962, 102-108.
https://doi.org/10.1016/j.jchromb.2014.05.037

Kostić N, Dotsikas Y, Jović N, Stevanović G, Malenović A, Medenica M. Vigabatrin in dried plasma spots: Validation of a novel LC-MS/MS method and application to clinical practice. in Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences. 2014;962:102-108.
doi:10.1016/j.jchromb.2014.05.037 .

Kostić, Nada, Dotsikas, Yannis, Jović, Nebojša, Stevanović, Galina, Malenović, Anđelija, Medenica, Mirjana, "Vigabatrin in dried plasma spots: Validation of a novel LC-MS/MS method and application to clinical practice" in Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 962 (2014):102-108,
https://doi.org/10.1016/j.jchromb.2014.05.037 . .

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 . .

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  - 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  - Kostić, Nada
AU  - Dotsikas, Yannis
AU  - Malenović, Anđelija
AU  - Jančić-Stojanović, Biljana
AU  - Rakić, Tijana
AU  - Ivanović, Darko
AU  - Medenica, Mirjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1967
AB  - In this article, a step-by-step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate-mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal-to-noise ratios, to be improved, enabling achievement of lower limit of detection values. Results from the current study demonstrate that optimization of parameters such as scan time, geometry of ion source, sheath and auxiliary gas pressure, capillary temperature, collision pressure and mobile phase composition can have a positive impact on sensitivity of LC-MS/MS methods. Optimization of LC and MS parameters led to a total increment of 53.9%, 83.3% and 95.7% in areas of derivatized vigabatrin, pregabalin and gabapentin, respectively, while for signal-to-noise values, an improvement of 140.0%, 93.6% and 124.0% was achieved, compared to autotune settings. After defining the final optimal conditions, a time-segmented method was validated for the determination of mentioned drugs in plasma. The method proved to be accurate and precise with excellent linearity for the tested concentration range (40.0ngml(-1)-10.0x10(3)ngml(-1)). Copyright
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Mass Spectrometry
T1  - Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design
VL  - 48
IS  - 7
SP  - 875
EP  - 884
DO  - 10.1002/jms.3236
ER  - 

@article{
author = "Kostić, Nada and Dotsikas, Yannis and Malenović, Anđelija and Jančić-Stojanović, Biljana and Rakić, Tijana and Ivanović, Darko and Medenica, Mirjana",
year = "2013",
abstract = "In this article, a step-by-step optimization procedure for improving analyte response with implementation of experimental design is described. Zwitterionic antiepileptics, namely vigabatrin, pregabalin and gabapentin, were chosen as model compounds to undergo chloroformate-mediated derivatization followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) analysis. Application of a planned stepwise optimization procedure allowed responses of analytes, expressed as areas and signal-to-noise ratios, to be improved, enabling achievement of lower limit of detection values. Results from the current study demonstrate that optimization of parameters such as scan time, geometry of ion source, sheath and auxiliary gas pressure, capillary temperature, collision pressure and mobile phase composition can have a positive impact on sensitivity of LC-MS/MS methods. Optimization of LC and MS parameters led to a total increment of 53.9%, 83.3% and 95.7% in areas of derivatized vigabatrin, pregabalin and gabapentin, respectively, while for signal-to-noise values, an improvement of 140.0%, 93.6% and 124.0% was achieved, compared to autotune settings. After defining the final optimal conditions, a time-segmented method was validated for the determination of mentioned drugs in plasma. The method proved to be accurate and precise with excellent linearity for the tested concentration range (40.0ngml(-1)-10.0x10(3)ngml(-1)). Copyright",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Mass Spectrometry",
title = "Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design",
volume = "48",
number = "7",
pages = "875-884",
doi = "10.1002/jms.3236"
}

Kostić, N., Dotsikas, Y., Malenović, A., Jančić-Stojanović, B., Rakić, T., Ivanović, D.,& Medenica, M.. (2013). Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design. in Journal of Mass Spectrometry
Wiley-Blackwell, Hoboken., 48(7), 875-884.
https://doi.org/10.1002/jms.3236

Kostić N, Dotsikas Y, Malenović A, Jančić-Stojanović B, Rakić T, Ivanović D, Medenica M. Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design. in Journal of Mass Spectrometry. 2013;48(7):875-884.
doi:10.1002/jms.3236 .

Kostić, Nada, Dotsikas, Yannis, Malenović, Anđelija, Jančić-Stojanović, Biljana, Rakić, Tijana, Ivanović, Darko, Medenica, Mirjana, "Stepwise optimization approach for improving LC-MS/MS analysis of zwitterionic antiepileptic drugs with implementation of experimental design" in Journal of Mass Spectrometry, 48, no. 7 (2013):875-884,
https://doi.org/10.1002/jms.3236 . .

TY  - JOUR
AU  - Malenović, Anđelija
AU  - Vemić, Ana
AU  - Kostić, Nada
AU  - Ivanović, D.
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1916
AB  - In this paper, a chemometrically assisted validation of RP-HPLC method, intended for the quantitative analysis of cefuroxime axetil (A and B), cefuroxime acid, cefuroxime lactone, cefuroxime axetil sulfoxide (A and B), a dagger(3)-cefuroxime axetil and anti cefuroxime axetil (A and B) in tablets, is presented. Since the successful separation could be achieved with the mobile phase containing only methanol and water, Luna C18 column was selected for the analysis. Under these circumstances, the optimization was quite straightforward and included only a fine tuning of the chromatographic conditions to reduce total run time and maintain the achieved separation. The established method was then subjected to the method validation and the required validation parameters were tested. For the robustness evaluation, a fractional factorial 2(4-1) design was utilized and factors that might significantly affect the system performance were defined. For the significant factors, the non-significant intervals were determined and the acceptable system suitability limit for resolution factor between cefuroxime axetil A and cefuroxime axetil a dagger(3) isomer (R (2)) was calculated. As the other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of cefuroxime axetil, cefuroxime acid, cefuroxime lactone, cefuroxime axetil sulfoxide, a dagger(3)-cefuroxime axetil and anti cefuroxime axetil in any laboratory under different circumstances is proven.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Evaluation of RP-HPLC Method Intended for the Analysis of Cefuroxime Axetil and ITS Impurities Supported by Experimental Design
VL  - 76
IS  - 5-6
SP  - 293
EP  - 298
DO  - 10.1007/s10337-013-2391-0
ER  - 

@article{
author = "Malenović, Anđelija and Vemić, Ana and Kostić, Nada and Ivanović, D.",
year = "2013",
abstract = "In this paper, a chemometrically assisted validation of RP-HPLC method, intended for the quantitative analysis of cefuroxime axetil (A and B), cefuroxime acid, cefuroxime lactone, cefuroxime axetil sulfoxide (A and B), a dagger(3)-cefuroxime axetil and anti cefuroxime axetil (A and B) in tablets, is presented. Since the successful separation could be achieved with the mobile phase containing only methanol and water, Luna C18 column was selected for the analysis. Under these circumstances, the optimization was quite straightforward and included only a fine tuning of the chromatographic conditions to reduce total run time and maintain the achieved separation. The established method was then subjected to the method validation and the required validation parameters were tested. For the robustness evaluation, a fractional factorial 2(4-1) design was utilized and factors that might significantly affect the system performance were defined. For the significant factors, the non-significant intervals were determined and the acceptable system suitability limit for resolution factor between cefuroxime axetil A and cefuroxime axetil a dagger(3) isomer (R (2)) was calculated. As the other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of cefuroxime axetil, cefuroxime acid, cefuroxime lactone, cefuroxime axetil sulfoxide, a dagger(3)-cefuroxime axetil and anti cefuroxime axetil in any laboratory under different circumstances is proven.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Evaluation of RP-HPLC Method Intended for the Analysis of Cefuroxime Axetil and ITS Impurities Supported by Experimental Design",
volume = "76",
number = "5-6",
pages = "293-298",
doi = "10.1007/s10337-013-2391-0"
}

Malenović, A., Vemić, A., Kostić, N.,& Ivanović, D.. (2013). Evaluation of RP-HPLC Method Intended for the Analysis of Cefuroxime Axetil and ITS Impurities Supported by Experimental Design. in Chromatographia
Springer Heidelberg, Heidelberg., 76(5-6), 293-298.
https://doi.org/10.1007/s10337-013-2391-0

Malenović A, Vemić A, Kostić N, Ivanović D. Evaluation of RP-HPLC Method Intended for the Analysis of Cefuroxime Axetil and ITS Impurities Supported by Experimental Design. in Chromatographia. 2013;76(5-6):293-298.
doi:10.1007/s10337-013-2391-0 .

Malenović, Anđelija, Vemić, Ana, Kostić, Nada, Ivanović, D., "Evaluation of RP-HPLC Method Intended for the Analysis of Cefuroxime Axetil and ITS Impurities Supported by Experimental Design" in Chromatographia, 76, no. 5-6 (2013):293-298,
https://doi.org/10.1007/s10337-013-2391-0 . .

TY  - JOUR
AU  - Kostić, Nada
AU  - Dotsikas, Yannis
AU  - Malenović, Anđelija
AU  - Medenica, Mirjana
PY  - 2013
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1911
AB  - In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances.
PB  - Elsevier Science BV, Amsterdam
T2  - Talanta
T1  - Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs
VL  - 116
SP  - 91
EP  - 99
DO  - 10.1016/j.talanta.2013.04.082
ER  - 

@article{
author = "Kostić, Nada and Dotsikas, Yannis and Malenović, Anđelija and Medenica, Mirjana",
year = "2013",
abstract = "In the current study, three antiepileptic drugs with zwitterionic properties, namely vigabatrin, pregabalin and gabapentin, were chosen as model analytes to undergo derivatization by applying various n-alkyl chloroformate/n-alcohol combinations, followed by LC-ESI-MS/MS analysis. The employment of 16 combinations per drug using methyl, ethyl, propyl or butyl chloroformate coupled with methanol, ethanol, propanol or butanol, greatly affected a series of parameters of the derivatives, such as retention time on C8 column, signal expressed via areas, limit of detection values, as well as the yields of the main and side reactions. Practically, even slight modification of n-alkyl group of either chloroformate or alcohol resulted in significant changes in the chromatographic and mass spectrometric behavior of the novel derivative. It was clearly demonstrated that all the estimated parameters were highly correlated with the length of n-alkyl groups of the involved chloroformate and alcohol. The most significant influence was monitored in peak area values, indicating that the length of the n-alkyl chain plays an important role in electrospray ionization efficiency. For this parameter, increasing the n-alkyl chain from methyl to butyl led to increment up to 2089%, 508.7% and 1075% for area values of derivatized vigabatrin, pregabalin and gabapentin, respectively. These changes affected also the corresponding values of limits of detection, with the estimated improvements up to 1553%, 397.7% and 875.0% for the aforementioned derivatized drugs, respectively. Besides the obvious utilization of these conclusions in the development of bioanalytical methods for these analytes with the current protocol, this study offers valuable data which can be useful in more general approaches, giving insights into the effects of this derivatization reaction and its performances.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Talanta",
title = "Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs",
volume = "116",
pages = "91-99",
doi = "10.1016/j.talanta.2013.04.082"
}

Kostić, N., Dotsikas, Y., Malenović, A.,& Medenica, M.. (2013). Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs. in Talanta
Elsevier Science BV, Amsterdam., 116, 91-99.
https://doi.org/10.1016/j.talanta.2013.04.082

Kostić N, Dotsikas Y, Malenović A, Medenica M. Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs. in Talanta. 2013;116:91-99.
doi:10.1016/j.talanta.2013.04.082 .

Kostić, Nada, Dotsikas, Yannis, Malenović, Anđelija, Medenica, Mirjana, "Effects of derivatization reagents consisting of n-alkyl chloroformate/n-alcohol combinations in LC-ESI-MS/MS analysis of zwitterionic antiepileptic drugs" in Talanta, 116 (2013):91-99,
https://doi.org/10.1016/j.talanta.2013.04.082 . .

TY  - JOUR
AU  - Malenović, Anđelija
AU  - Jovanović, Marko
AU  - Petrović, Sonja
AU  - Kostić, Nada
AU  - Vemić, Ana
AU  - Jančić-Stojanović, Biljana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1749
AB  - In this article, the multiobjective optimization of reversed-phase high-performance liquid chromatography (RP-HPLC) method for the analysis of folic acid and its two impurities, p-aminobenzoic acid and N-(4-aminobenzoyl)-L-glutamic acid, is presented. During the preliminary study, the independent variables whose impact should be further examined in the optimization were defined (acetonitrile content in the mobile phase, molarity of sodium 1-heptanesulfonate in the aqueous phase, and pH of the aqueous phase). The face-centered central composite design was chosen for the method optimization. As the dependent variables, the separation between the impurities and the retention factor of folic acid were followed. The analysis of variance (ANOVA) test was done, and good correlation among results was confirmed. For the more accurate and reliable optimization, Derringer's desirability function was applied. On the basis of restrictions adopted for the selected targets, the resulting optimal composition of the mobile phase was acetonitrile -3 mM sodium 1-heptanesulfonate (5.3:94.7 V/V), pH of the aqueous phase adjusted to 2.1 with the concentrated ortho-phosphoric acid. Furthermore, the method was subjected to method validation. It proved to be reliable and suitable for the routine analysis of investigated substances in active pharmaceutical ingredients, as well as in pharmaceutical preparations.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Instrumentation Science & Technology
T1  - Optimization of liquid chromatographic method for the separation of folic acid and its two impurities
VL  - 40
IS  - 2-3
SP  - 138
EP  - 149
DO  - 10.1080/10739149.2011.651670
ER  - 

@article{
author = "Malenović, Anđelija and Jovanović, Marko and Petrović, Sonja and Kostić, Nada and Vemić, Ana and Jančić-Stojanović, Biljana",
year = "2012",
abstract = "In this article, the multiobjective optimization of reversed-phase high-performance liquid chromatography (RP-HPLC) method for the analysis of folic acid and its two impurities, p-aminobenzoic acid and N-(4-aminobenzoyl)-L-glutamic acid, is presented. During the preliminary study, the independent variables whose impact should be further examined in the optimization were defined (acetonitrile content in the mobile phase, molarity of sodium 1-heptanesulfonate in the aqueous phase, and pH of the aqueous phase). The face-centered central composite design was chosen for the method optimization. As the dependent variables, the separation between the impurities and the retention factor of folic acid were followed. The analysis of variance (ANOVA) test was done, and good correlation among results was confirmed. For the more accurate and reliable optimization, Derringer's desirability function was applied. On the basis of restrictions adopted for the selected targets, the resulting optimal composition of the mobile phase was acetonitrile -3 mM sodium 1-heptanesulfonate (5.3:94.7 V/V), pH of the aqueous phase adjusted to 2.1 with the concentrated ortho-phosphoric acid. Furthermore, the method was subjected to method validation. It proved to be reliable and suitable for the routine analysis of investigated substances in active pharmaceutical ingredients, as well as in pharmaceutical preparations.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Instrumentation Science & Technology",
title = "Optimization of liquid chromatographic method for the separation of folic acid and its two impurities",
volume = "40",
number = "2-3",
pages = "138-149",
doi = "10.1080/10739149.2011.651670"
}

Malenović, A., Jovanović, M., Petrović, S., Kostić, N., Vemić, A.,& Jančić-Stojanović, B.. (2012). Optimization of liquid chromatographic method for the separation of folic acid and its two impurities. in Instrumentation Science & Technology
Taylor & Francis Inc, Philadelphia., 40(2-3), 138-149.
https://doi.org/10.1080/10739149.2011.651670

Malenović A, Jovanović M, Petrović S, Kostić N, Vemić A, Jančić-Stojanović B. Optimization of liquid chromatographic method for the separation of folic acid and its two impurities. in Instrumentation Science & Technology. 2012;40(2-3):138-149.
doi:10.1080/10739149.2011.651670 .

Malenović, Anđelija, Jovanović, Marko, Petrović, Sonja, Kostić, Nada, Vemić, Ana, Jančić-Stojanović, Biljana, "Optimization of liquid chromatographic method for the separation of folic acid and its two impurities" in Instrumentation Science & Technology, 40, no. 2-3 (2012):138-149,
https://doi.org/10.1080/10739149.2011.651670 . .

TY  - JOUR
AU  - Jovović, M.
AU  - Kostić, Nada
AU  - Jančić-Stojanović, Biljana
AU  - Malenović, Anđelija
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1696
AB  - In this study, a development of stability indicating method (SIM) that could be used to detect a decrease in the amount of tropicamide and benzalkonium chloride due to their degradation is described. In the method development, stress samples should be used. Benzalkanium chloride proved to be very stable under all stress conditions. Acid stress with 0.1 M HCl C led to 10% degradation of tropicamide alter >= 30 min. The alkaline stress with 1 M NaOH at 70 degrees C induced faster degradation and more than 20% of tropicamide degraded after 30 mm. On the other hand, tropicamide proved to be exceptionally stable to oxidative stress and no degradation was observed with 30% H2O2 even alter heating at 70 degrees C for 90 min. The mobile phase consisted of acetonitrile and water phase 70:30v/v (water phase: 5 mM sodium heptan sulphonate and 1% triethylamine MA) with phi of the mobile phase adjusted to 3.5 with ortophosphoric acid. The flaw rate was 2 mL min(-1). In order to confirm the method adequacy for intended purpose, the proposed method was validated. Finally, the proper validation of developed SIM performed according to the official guidelines proved that the method accomplishes its intended purpose.
PB  - Taylor & Francis Inc, Philadelphia
T2  - Journal of Liquid Chromatography & Related Technologies
T1  - Investigation of tropicamide and benzalkonium chloride stability using liquid chromatography
VL  - 35
IS  - 1-4
SP  - 231
EP  - 239
DO  - 10.1080/10826076.2011.597072
ER  - 

@article{
author = "Jovović, M. and Kostić, Nada and Jančić-Stojanović, Biljana and Malenović, Anđelija",
year = "2012",
abstract = "In this study, a development of stability indicating method (SIM) that could be used to detect a decrease in the amount of tropicamide and benzalkonium chloride due to their degradation is described. In the method development, stress samples should be used. Benzalkanium chloride proved to be very stable under all stress conditions. Acid stress with 0.1 M HCl C led to 10% degradation of tropicamide alter >= 30 min. The alkaline stress with 1 M NaOH at 70 degrees C induced faster degradation and more than 20% of tropicamide degraded after 30 mm. On the other hand, tropicamide proved to be exceptionally stable to oxidative stress and no degradation was observed with 30% H2O2 even alter heating at 70 degrees C for 90 min. The mobile phase consisted of acetonitrile and water phase 70:30v/v (water phase: 5 mM sodium heptan sulphonate and 1% triethylamine MA) with phi of the mobile phase adjusted to 3.5 with ortophosphoric acid. The flaw rate was 2 mL min(-1). In order to confirm the method adequacy for intended purpose, the proposed method was validated. Finally, the proper validation of developed SIM performed according to the official guidelines proved that the method accomplishes its intended purpose.",
publisher = "Taylor & Francis Inc, Philadelphia",
journal = "Journal of Liquid Chromatography & Related Technologies",
title = "Investigation of tropicamide and benzalkonium chloride stability using liquid chromatography",
volume = "35",
number = "1-4",
pages = "231-239",
doi = "10.1080/10826076.2011.597072"
}

Jovović, M., Kostić, N., Jančić-Stojanović, B.,& Malenović, A.. (2012). Investigation of tropicamide and benzalkonium chloride stability using liquid chromatography. in Journal of Liquid Chromatography & Related Technologies
Taylor & Francis Inc, Philadelphia., 35(1-4), 231-239.
https://doi.org/10.1080/10826076.2011.597072

Jovović M, Kostić N, Jančić-Stojanović B, Malenović A. Investigation of tropicamide and benzalkonium chloride stability using liquid chromatography. in Journal of Liquid Chromatography & Related Technologies. 2012;35(1-4):231-239.
doi:10.1080/10826076.2011.597072 .

Jovović, M., Kostić, Nada, Jančić-Stojanović, Biljana, Malenović, Anđelija, "Investigation of tropicamide and benzalkonium chloride stability using liquid chromatography" in Journal of Liquid Chromatography & Related Technologies, 35, no. 1-4 (2012):231-239,
https://doi.org/10.1080/10826076.2011.597072 . .

TY  - JOUR
AU  - Malenović, Anđelija
AU  - Jančić-Stojanović, Biljana
AU  - Kostić, Nada
AU  - Ivanović, Darko
AU  - Medenica, Mirjana
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1521
AB  - Artificial Neural Networks (ANNs) present a powerful tool for the modeling of chromatographic retention. In this paper, the main objective was to use ANNs as a tool in modeling of atorvastatin and its impurities' retention in a micellar liquid chromatography (MLC) protocol. Factors referred to MLC were evaluated through 30 experiments defined by the Central Composite Design. In this manner, 5-x-3 topology as a starting point for ANNs' optimization was defined too. In the next step, in order to set the network with the best performance, network optimization was done. In the first part, the number of nodes in the hidden layer and the number of experimental data points in training set were simultaneously varied, and their importance was estimated with suitable statistical parameters. Furthermore, a series of training algorithms was applied to the current network. The Back Propagation, Conjugate Gradient-descent, Quick Propagation, Quasi-Newton, and Delta-bar-Delta algorithms were used to obtain the optimal network. Finally, the predictive ability of the optimized neural network was confirmed through several statistical tests. The obtained network showed high ability to predict chromatographic retention of atorvastatin and its impurities in MLC.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Optimization of Artificial Neural Networks for Modeling of Atorvastatin and Its Impurities Retention in Micellar Liquid Chromatography
VL  - 73
IS  - 9-10
SP  - 993
EP  - 998
DO  - 10.1007/s10337-011-1994-6
ER  - 

@article{
author = "Malenović, Anđelija and Jančić-Stojanović, Biljana and Kostić, Nada and Ivanović, Darko and Medenica, Mirjana",
year = "2011",
abstract = "Artificial Neural Networks (ANNs) present a powerful tool for the modeling of chromatographic retention. In this paper, the main objective was to use ANNs as a tool in modeling of atorvastatin and its impurities' retention in a micellar liquid chromatography (MLC) protocol. Factors referred to MLC were evaluated through 30 experiments defined by the Central Composite Design. In this manner, 5-x-3 topology as a starting point for ANNs' optimization was defined too. In the next step, in order to set the network with the best performance, network optimization was done. In the first part, the number of nodes in the hidden layer and the number of experimental data points in training set were simultaneously varied, and their importance was estimated with suitable statistical parameters. Furthermore, a series of training algorithms was applied to the current network. The Back Propagation, Conjugate Gradient-descent, Quick Propagation, Quasi-Newton, and Delta-bar-Delta algorithms were used to obtain the optimal network. Finally, the predictive ability of the optimized neural network was confirmed through several statistical tests. The obtained network showed high ability to predict chromatographic retention of atorvastatin and its impurities in MLC.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Optimization of Artificial Neural Networks for Modeling of Atorvastatin and Its Impurities Retention in Micellar Liquid Chromatography",
volume = "73",
number = "9-10",
pages = "993-998",
doi = "10.1007/s10337-011-1994-6"
}

Malenović, A., Jančić-Stojanović, B., Kostić, N., Ivanović, D.,& Medenica, M.. (2011). Optimization of Artificial Neural Networks for Modeling of Atorvastatin and Its Impurities Retention in Micellar Liquid Chromatography. in Chromatographia
Springer Heidelberg, Heidelberg., 73(9-10), 993-998.
https://doi.org/10.1007/s10337-011-1994-6

Malenović A, Jančić-Stojanović B, Kostić N, Ivanović D, Medenica M. Optimization of Artificial Neural Networks for Modeling of Atorvastatin and Its Impurities Retention in Micellar Liquid Chromatography. in Chromatographia. 2011;73(9-10):993-998.
doi:10.1007/s10337-011-1994-6 .

Malenović, Anđelija, Jančić-Stojanović, Biljana, Kostić, Nada, Ivanović, Darko, Medenica, Mirjana, "Optimization of Artificial Neural Networks for Modeling of Atorvastatin and Its Impurities Retention in Micellar Liquid Chromatography" in Chromatographia, 73, no. 9-10 (2011):993-998,
https://doi.org/10.1007/s10337-011-1994-6 . .

TY  - JOUR
AU  - Jančić-Stojanović, Biljana
AU  - Rakić, Tijana
AU  - Kostić, Nada
AU  - Vemić, Ana
AU  - Malenović, Anđelija
AU  - Ivanović, D.
AU  - Medenica, Mirjana
PY  - 2011
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1477
AB  - In this paper a new chromatographic response function (CRF) is designed and proposed for utilization in the optimization strategies. The function capability to represent the overall quality of a experimentally obtained chromatograms was compared to the other two objective functions and proved to give more accurate and reliable results. The new CRF has improved concept of separation and time term estimation. It reflects all important defects of the chromatogram such as the appearance of asymmetrical or overlapping peaks and prolonged elution time and allows the appropriate weighting of each of them. The LC separation of raloxifene and its four impurities was evaluated through the central composite design experimental plan choosing the new CRF to be the only output of the system. The function demonstrated the ability to judge the impact of the complex interactions of the selected chromatographic parameters (acetonitrile content in the mobile phase, sodium dodecyl sulfate concentration in the water phase, pH of the mobile phase and column temperature) on the mixture behavior and led to the determination of the optimal separation conditions. The newly developed CRF proved to have the advanced performances and it presents the important step forward in the optimization of the chromatographic separation.
PB  - Elsevier Science BV, Amsterdam
T2  - Talanta
T1  - Advancement in optimization tactic achieved by newly developed chromatographic response function: Application to LC separation of raloxifene and its impurities
VL  - 85
IS  - 3
SP  - 1453
EP  - 1460
DO  - 10.1016/j.talanta.2011.06.029
ER  - 

@article{
author = "Jančić-Stojanović, Biljana and Rakić, Tijana and Kostić, Nada and Vemić, Ana and Malenović, Anđelija and Ivanović, D. and Medenica, Mirjana",
year = "2011",
abstract = "In this paper a new chromatographic response function (CRF) is designed and proposed for utilization in the optimization strategies. The function capability to represent the overall quality of a experimentally obtained chromatograms was compared to the other two objective functions and proved to give more accurate and reliable results. The new CRF has improved concept of separation and time term estimation. It reflects all important defects of the chromatogram such as the appearance of asymmetrical or overlapping peaks and prolonged elution time and allows the appropriate weighting of each of them. The LC separation of raloxifene and its four impurities was evaluated through the central composite design experimental plan choosing the new CRF to be the only output of the system. The function demonstrated the ability to judge the impact of the complex interactions of the selected chromatographic parameters (acetonitrile content in the mobile phase, sodium dodecyl sulfate concentration in the water phase, pH of the mobile phase and column temperature) on the mixture behavior and led to the determination of the optimal separation conditions. The newly developed CRF proved to have the advanced performances and it presents the important step forward in the optimization of the chromatographic separation.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Talanta",
title = "Advancement in optimization tactic achieved by newly developed chromatographic response function: Application to LC separation of raloxifene and its impurities",
volume = "85",
number = "3",
pages = "1453-1460",
doi = "10.1016/j.talanta.2011.06.029"
}

Jančić-Stojanović, B., Rakić, T., Kostić, N., Vemić, A., Malenović, A., Ivanović, D.,& Medenica, M.. (2011). Advancement in optimization tactic achieved by newly developed chromatographic response function: Application to LC separation of raloxifene and its impurities. in Talanta
Elsevier Science BV, Amsterdam., 85(3), 1453-1460.
https://doi.org/10.1016/j.talanta.2011.06.029

Jančić-Stojanović B, Rakić T, Kostić N, Vemić A, Malenović A, Ivanović D, Medenica M. Advancement in optimization tactic achieved by newly developed chromatographic response function: Application to LC separation of raloxifene and its impurities. in Talanta. 2011;85(3):1453-1460.
doi:10.1016/j.talanta.2011.06.029 .

Jančić-Stojanović, Biljana, Rakić, Tijana, Kostić, Nada, Vemić, Ana, Malenović, Anđelija, Ivanović, D., Medenica, Mirjana, "Advancement in optimization tactic achieved by newly developed chromatographic response function: Application to LC separation of raloxifene and its impurities" in Talanta, 85, no. 3 (2011):1453-1460,
https://doi.org/10.1016/j.talanta.2011.06.029 . .