TY  - CONF
AU  - Malenović, Anđelija
AU  - Rmandić, Milena
AU  - Dotsikas, Yannis
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5554
AB  - When using DBS as sample collection tool, several specific factors can contribute to assay bias and compromise regulatory-based acceptance criteria. Certain factors like hematocrit (Hct) level, pipettes, sample volume and laboratory personnel have a potential to contribute bioanalytical method bias inherently. The proper understanding of Hct effect and the efficient resolving of the related concerns may determine the future of DBS sampling practice in regulated bioanalysis. Therefore, we aimed at reaching a procedure that enables accurate and precise blood spotting onto the filter paper by simultaneous investigation of factors that were suggested to be scientifically relevant in this context. The effects of five qualitative factors - temperature of blood samples, type of pipettes, pipetting technique, age of blood samples and analyst - were investigated using a multilevel categorical D-optimal design. Five responses were observed in the study (RSD22%Hct, RSD30%Hct, RSD39%Hct, RSD51%Hct, RSD62%Hct) as they can provide information on the influence of factor settings on the consistency of DBS areas. DBS cards with four spot replicates, corresponding to particular combination of investigated factors defined by experimental plan, were scanned and the area of blood spots was determined by image processing. The principle of backward elimination was applied in computation of the adequate qualitative linear mathematical models with added appropriate two-factor interactions to relate selected responses with studied factors. It was concluded that %RSD value of DBS, regardless Hct levels, is completely independent of type of pipettes and age of blood samples, but can significantly be affected by blood sample temperature, pipetting technique and level of training of analyst. Consequently, the procedure for precise and accurate formation of DBS of uniform area, regardless the Hct value, implies samples at body/room temperature, reversed pipetting technique for rigorous delivery of a sample volume onto the card and a properly trained analyst for handling blood samples. The adequacy of the suggested procedure was confirmed by a verification experiment. Identification of the factors affecting the consistency of DBS formation provided the evidence that this contribution to total assay bias can be successfully controlled and reduced.
C3  - IV Poznańska Konferencja Naukowo – Szkoleniowej - „Modern pharmaceutical and biomedical analytics in health care”
T1  - Critical issues in quantitative bioanalysis of Dried Blood Spot samples
SP  - 48
EP  - 48
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5554
ER  - 

@conference{
author = "Malenović, Anđelija and Rmandić, Milena and Dotsikas, Yannis",
year = "2023",
abstract = "When using DBS as sample collection tool, several specific factors can contribute to assay bias and compromise regulatory-based acceptance criteria. Certain factors like hematocrit (Hct) level, pipettes, sample volume and laboratory personnel have a potential to contribute bioanalytical method bias inherently. The proper understanding of Hct effect and the efficient resolving of the related concerns may determine the future of DBS sampling practice in regulated bioanalysis. Therefore, we aimed at reaching a procedure that enables accurate and precise blood spotting onto the filter paper by simultaneous investigation of factors that were suggested to be scientifically relevant in this context. The effects of five qualitative factors - temperature of blood samples, type of pipettes, pipetting technique, age of blood samples and analyst - were investigated using a multilevel categorical D-optimal design. Five responses were observed in the study (RSD22%Hct, RSD30%Hct, RSD39%Hct, RSD51%Hct, RSD62%Hct) as they can provide information on the influence of factor settings on the consistency of DBS areas. DBS cards with four spot replicates, corresponding to particular combination of investigated factors defined by experimental plan, were scanned and the area of blood spots was determined by image processing. The principle of backward elimination was applied in computation of the adequate qualitative linear mathematical models with added appropriate two-factor interactions to relate selected responses with studied factors. It was concluded that %RSD value of DBS, regardless Hct levels, is completely independent of type of pipettes and age of blood samples, but can significantly be affected by blood sample temperature, pipetting technique and level of training of analyst. Consequently, the procedure for precise and accurate formation of DBS of uniform area, regardless the Hct value, implies samples at body/room temperature, reversed pipetting technique for rigorous delivery of a sample volume onto the card and a properly trained analyst for handling blood samples. The adequacy of the suggested procedure was confirmed by a verification experiment. Identification of the factors affecting the consistency of DBS formation provided the evidence that this contribution to total assay bias can be successfully controlled and reduced.",
journal = "IV Poznańska Konferencja Naukowo – Szkoleniowej - „Modern pharmaceutical and biomedical analytics in health care”",
title = "Critical issues in quantitative bioanalysis of Dried Blood Spot samples",
pages = "48-48",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5554"
}

Malenović, A., Rmandić, M.,& Dotsikas, Y.. (2023). Critical issues in quantitative bioanalysis of Dried Blood Spot samples. in IV Poznańska Konferencja Naukowo – Szkoleniowej - „Modern pharmaceutical and biomedical analytics in health care”, 48-48.
https://hdl.handle.net/21.15107/rcub_farfar_5554

Malenović A, Rmandić M, Dotsikas Y. Critical issues in quantitative bioanalysis of Dried Blood Spot samples. in IV Poznańska Konferencja Naukowo – Szkoleniowej - „Modern pharmaceutical and biomedical analytics in health care”. 2023;:48-48.
https://hdl.handle.net/21.15107/rcub_farfar_5554 .

Malenović, Anđelija, Rmandić, Milena, Dotsikas, Yannis, "Critical issues in quantitative bioanalysis of Dried Blood Spot samples" in IV Poznańska Konferencja Naukowo – Szkoleniowej - „Modern pharmaceutical and biomedical analytics in health care” (2023):48-48,
https://hdl.handle.net/21.15107/rcub_farfar_5554 .

TY  - JOUR
AU  - Rmandić, Milena
AU  - Vasilić, Đorđe
AU  - Rašević, Marija
AU  - Zečević, Mira
AU  - Otašević, Biljana
AU  - Protić, Ana
AU  - Malenović, Anđelija
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5055
AB  - In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (t_imp. V, t_imp. V − t_imp. I, S and <WUSP>) was studied by Box–Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained. The design space was computed (π ≥ 80%), and a working point was selected: initial methanol fraction 38.5%, final methanol fraction 77.5%, and gradient duration 16.25 min. Furthermore, the quantitative robustness of the developed method was tested using the Plackett–Burman design. P_imp II and P_imp V were found to be significantly affected, the first by mobile phase flow rate and the second by gradient duration. Finally, the method was validated, and its reliability for routine quality control in capsules was confirmed.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination
VL  - 16
IS  - 9
DO  - 10.3390/ph16091296
ER  - 

@article{
author = "Rmandić, Milena and Vasilić, Đorđe and Rašević, Marija and Zečević, Mira and Otašević, Biljana and Protić, Ana and Malenović, Anđelija",
year = "2023",
abstract = "In this study, an AQbD-compliant chaotropic chromatography method for ziprasidone and the determination of its five impurities was developed. The influence of critical method parameters (initial and final methanol fraction in the mobile phase, gradient duration) on the set of selected critical method attributes (t_imp. V, t_imp. V − t_imp. I, S and <WUSP>) was studied by Box–Behnken design. The errors resulting from the calculation of the model coefficients were propagated to the selected responses by Monte Carlo simulations, and their predictive distribution was obtained. The design space was computed (π ≥ 80%), and a working point was selected: initial methanol fraction 38.5%, final methanol fraction 77.5%, and gradient duration 16.25 min. Furthermore, the quantitative robustness of the developed method was tested using the Plackett–Burman design. P_imp II and P_imp V were found to be significantly affected, the first by mobile phase flow rate and the second by gradient duration. Finally, the method was validated, and its reliability for routine quality control in capsules was confirmed.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination",
volume = "16",
number = "9",
doi = "10.3390/ph16091296"
}

Rmandić, M., Vasilić, Đ., Rašević, M., Zečević, M., Otašević, B., Protić, A.,& Malenović, A.. (2023). Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination. in Pharmaceuticals
MDPI., 16(9).
https://doi.org/10.3390/ph16091296

Rmandić M, Vasilić Đ, Rašević M, Zečević M, Otašević B, Protić A, Malenović A. Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination. in Pharmaceuticals. 2023;16(9).
doi:10.3390/ph16091296 .

Rmandić, Milena, Vasilić, Đorđe, Rašević, Marija, Zečević, Mira, Otašević, Biljana, Protić, Ana, Malenović, Anđelija, "Development of Analytical Quality by Design Compliant Chaotropic Chromatography Method for Ziprasidone and Its Five Impurities Determination" in Pharmaceuticals, 16, no. 9 (2023),
https://doi.org/10.3390/ph16091296 . .

TY  - JOUR
AU  - Ćirić, Ana
AU  - Milinković Budinčić, Jelena
AU  - Dobričić, Vladimir
AU  - Rmandić, Milena
AU  - Barudžija, Tanja
AU  - Malenović, Anđelija
AU  - Petrović, Lidija
AU  - Đekić, Ljiljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4272
AB  - Escin is an amphiphilic and weakly acidic drug that oral administration may lead to the irritation of gastric mucosa. The entrapment of escin into chitosan (CH)/xanthan gum (XG)-based polyelectrolyte complexes (PECs) can facilitate controlled drug release which may be beneficial for the reduction of its side effects. This study aimed to investigate the influence of escin content and drying method on the formation, physicochemical, and controlled, pH-dependent drug release properties of CH/XG-based PECs. Measurements of transmittance, con- ductivity, and rheological characterization confirmed the formation of CH/XG-based PECs with escin entrapped at escin-to-polymers mass ratios 1:1, 1:2, and 1:4. Ambient-dried PECs had higher yield, entrapment efficiency, and escin content in comparison with spray-dried ones. FT-IR spectra confirmed the interactions between CH, XG, and escin, which were stronger in ambient-dried PECs. PXRD and DSC analyses showed the amorphous escin character in all dry PECs, regardless of the drying method. The most promising controlled and pH-dependent in vitro escin release was from the ambient-dried PEC at the escin-to-polymers mass ratio of 1:1. For that reason and due to the highest yield and entrapment efficiency, this carrier has the potential to prevent the irritation of gastric mucosa after oral administration of escin.
PB  - Elsevier B.V.
T2  - International Journal of Biological Macromolecules
T1  - Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin
VL  - 221
SP  - 48
EP  - 60
DO  - 10.1016/j.ijbiomac.2022.08.190
ER  - 

@article{
author = "Ćirić, Ana and Milinković Budinčić, Jelena and Dobričić, Vladimir and Rmandić, Milena and Barudžija, Tanja and Malenović, Anđelija and Petrović, Lidija and Đekić, Ljiljana",
year = "2022",
abstract = "Escin is an amphiphilic and weakly acidic drug that oral administration may lead to the irritation of gastric mucosa. The entrapment of escin into chitosan (CH)/xanthan gum (XG)-based polyelectrolyte complexes (PECs) can facilitate controlled drug release which may be beneficial for the reduction of its side effects. This study aimed to investigate the influence of escin content and drying method on the formation, physicochemical, and controlled, pH-dependent drug release properties of CH/XG-based PECs. Measurements of transmittance, con- ductivity, and rheological characterization confirmed the formation of CH/XG-based PECs with escin entrapped at escin-to-polymers mass ratios 1:1, 1:2, and 1:4. Ambient-dried PECs had higher yield, entrapment efficiency, and escin content in comparison with spray-dried ones. FT-IR spectra confirmed the interactions between CH, XG, and escin, which were stronger in ambient-dried PECs. PXRD and DSC analyses showed the amorphous escin character in all dry PECs, regardless of the drying method. The most promising controlled and pH-dependent in vitro escin release was from the ambient-dried PEC at the escin-to-polymers mass ratio of 1:1. For that reason and due to the highest yield and entrapment efficiency, this carrier has the potential to prevent the irritation of gastric mucosa after oral administration of escin.",
publisher = "Elsevier B.V.",
journal = "International Journal of Biological Macromolecules",
title = "Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin",
volume = "221",
pages = "48-60",
doi = "10.1016/j.ijbiomac.2022.08.190"
}

Ćirić, A., Milinković Budinčić, J., Dobričić, V., Rmandić, M., Barudžija, T., Malenović, A., Petrović, L.,& Đekić, L.. (2022). Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin. in International Journal of Biological Macromolecules
Elsevier B.V.., 221, 48-60.
https://doi.org/10.1016/j.ijbiomac.2022.08.190

Ćirić A, Milinković Budinčić J, Dobričić V, Rmandić M, Barudžija T, Malenović A, Petrović L, Đekić L. Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin. in International Journal of Biological Macromolecules. 2022;221:48-60.
doi:10.1016/j.ijbiomac.2022.08.190 .

Ćirić, Ana, Milinković Budinčić, Jelena, Dobričić, Vladimir, Rmandić, Milena, Barudžija, Tanja, Malenović, Anđelija, Petrović, Lidija, Đekić, Ljiljana, "Evaluation of chitosan/xanthan gum polyelectrolyte complexes potential for pH-dependent oral delivery of escin" in International Journal of Biological Macromolecules, 221 (2022):48-60,
https://doi.org/10.1016/j.ijbiomac.2022.08.190 . .

TY  - JOUR
AU  - Ćirić, Ana
AU  - Milinković Budinčić, Jelena
AU  - Medarević, Đorđe
AU  - Dobričić, Vladimir
AU  - Rmandić, Milena
AU  - Barudžija, Tanja
AU  - Malenović, Anđelija
AU  - Petrović, Lidija
AU  - Đekić, Ljiljana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4179
AB  - Polyelectrolyte complexes (PECs) are attractive carriers with recognized potential to
enhance oral delivery of poorly soluble high-dosed low-molecular-weight drugs. The formulation
of solid oral dosage forms requires the drying of PECs, which may affect their physicochemical
and biopharmaceutical properties. The aim of this study was to investigate the effect of spray-
drying on the properties of ibuprofen-loaded chitosan/xanthan gum PECs and to assess the drug
release kinetics from such PECs filled into hard capsules in comparison with corresponding PECs
which are dried under ambient conditions. The yield, ibuprofen content, entrapment efficiency,
and residual moisture content of spray-dried PECs were lower than those of ambient-dried PECs.
Better flowability of spray-dried PECs was attributed to the almost spherical particle shape,
shown by scanning electron microscopy. DSC and PXRD analysis confirmed the amorphization
of ibuprofen during spray-drying. All the investigated PECs, obtained by drying under ambient
conditions as well as by spray-drying, had high rehydration capacity both in 0.1 M hydrochloric
acid (pH 1.2) and phosphate buffer pH 7.4. In vitro ibuprofen release from dried PECs was
controlled during 12 h with the release of approximately 30% of entrapped ibuprofen. Spray-dried
PECs provided better control of ibuprofen diffusion from the carrier compared to the ambient-
dried ones.
AB  - Polielektrolitni kompleksi (PEK) su atraktivni nosači sa potencijalom poboljšanja peroralne isporuke slabo rastvorljivih visokodoziranih lekovitih supstanci niske molekulske mase. Formulisanje čvrstih oralnih farmaceutskih oblika na bazi PEK zahteva njihovo sušenje, što može uticati na fizičko-hemijska i biofarmaceutska svojstva kompleksa. Cilj ove studije bio je da se ispita efekat sušenja raspršivanjem na svojstva PEK hitozana i ksantan gume u koje je inkorporiran ibuprofen i da se proceni kinetika oslobađanja lekovite supstance iz takvih PEK napunjenih u tvrde kapsule u poređenju sa odgovarajućim PEK koji su sušeni pod ambijentalnim uslovima. Prinos, sadržaj ibuprofena, efikasnost inkorporiranja i sadržaj vlage PEK sušenih raspršivanjem bili su niži nego kod PEK sušenih pod ambijentalnim uslovima. Bolja protočnost PEK osušenih raspršivanjem je posledica skoro sfernog oblika čestica, što je pokazano skenirajućom elektronskom mikroskopijom. Rezultati DSC i PXRD analiza su potvrdili amorfizaciju ibuprofena tokom sušenja raspršivanjem. Ispitivani PEK osušeni pod različitim uslovima imali su visoku sposobnost rehidratacije u 0,1 M hlorovodoničnoj kiselini (pH 1,2) i fosfatnom puferu pH 7,4. In vitro oslobađanje ibuprofena iz osušenih PEK bilo je kontrolisano tokom 12 h uz oslobađanje približno 30% inkorporiranog ibuprofena. PEK sušeni raspršivanjem obezbedili su bolju kontrolu difuzije ibuprofena iz nosača u poređenju sa onima sušenim pod ambijentalnim uslovima.
PB  - Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen
T1  - Uticaj postupka sušenja raspršivanjem na svojstva polielektrolitnih kompleksa hitozana i ksantan gume kao nosača za peroralnu isporuku ibuprofena
VL  - 72
IS  - 1
SP  - 36
EP  - 60
DO  - 10.5937/arhfarm72-35133
ER  - 

@article{
author = "Ćirić, Ana and Milinković Budinčić, Jelena and Medarević, Đorđe and Dobričić, Vladimir and Rmandić, Milena and Barudžija, Tanja and Malenović, Anđelija and Petrović, Lidija and Đekić, Ljiljana",
year = "2022",
abstract = "Polyelectrolyte complexes (PECs) are attractive carriers with recognized potential to
enhance oral delivery of poorly soluble high-dosed low-molecular-weight drugs. The formulation
of solid oral dosage forms requires the drying of PECs, which may affect their physicochemical
and biopharmaceutical properties. The aim of this study was to investigate the effect of spray-
drying on the properties of ibuprofen-loaded chitosan/xanthan gum PECs and to assess the drug
release kinetics from such PECs filled into hard capsules in comparison with corresponding PECs
which are dried under ambient conditions. The yield, ibuprofen content, entrapment efficiency,
and residual moisture content of spray-dried PECs were lower than those of ambient-dried PECs.
Better flowability of spray-dried PECs was attributed to the almost spherical particle shape,
shown by scanning electron microscopy. DSC and PXRD analysis confirmed the amorphization
of ibuprofen during spray-drying. All the investigated PECs, obtained by drying under ambient
conditions as well as by spray-drying, had high rehydration capacity both in 0.1 M hydrochloric
acid (pH 1.2) and phosphate buffer pH 7.4. In vitro ibuprofen release from dried PECs was
controlled during 12 h with the release of approximately 30% of entrapped ibuprofen. Spray-dried
PECs provided better control of ibuprofen diffusion from the carrier compared to the ambient-
dried ones., Polielektrolitni kompleksi (PEK) su atraktivni nosači sa potencijalom poboljšanja peroralne isporuke slabo rastvorljivih visokodoziranih lekovitih supstanci niske molekulske mase. Formulisanje čvrstih oralnih farmaceutskih oblika na bazi PEK zahteva njihovo sušenje, što može uticati na fizičko-hemijska i biofarmaceutska svojstva kompleksa. Cilj ove studije bio je da se ispita efekat sušenja raspršivanjem na svojstva PEK hitozana i ksantan gume u koje je inkorporiran ibuprofen i da se proceni kinetika oslobađanja lekovite supstance iz takvih PEK napunjenih u tvrde kapsule u poređenju sa odgovarajućim PEK koji su sušeni pod ambijentalnim uslovima. Prinos, sadržaj ibuprofena, efikasnost inkorporiranja i sadržaj vlage PEK sušenih raspršivanjem bili su niži nego kod PEK sušenih pod ambijentalnim uslovima. Bolja protočnost PEK osušenih raspršivanjem je posledica skoro sfernog oblika čestica, što je pokazano skenirajućom elektronskom mikroskopijom. Rezultati DSC i PXRD analiza su potvrdili amorfizaciju ibuprofena tokom sušenja raspršivanjem. Ispitivani PEK osušeni pod različitim uslovima imali su visoku sposobnost rehidratacije u 0,1 M hlorovodoničnoj kiselini (pH 1,2) i fosfatnom puferu pH 7,4. In vitro oslobađanje ibuprofena iz osušenih PEK bilo je kontrolisano tokom 12 h uz oslobađanje približno 30% inkorporiranog ibuprofena. PEK sušeni raspršivanjem obezbedili su bolju kontrolu difuzije ibuprofena iz nosača u poređenju sa onima sušenim pod ambijentalnim uslovima.",
publisher = "Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen, Uticaj postupka sušenja raspršivanjem na svojstva polielektrolitnih kompleksa hitozana i ksantan gume kao nosača za peroralnu isporuku ibuprofena",
volume = "72",
number = "1",
pages = "36-60",
doi = "10.5937/arhfarm72-35133"
}

Ćirić, A., Milinković Budinčić, J., Medarević, Đ., Dobričić, V., Rmandić, M., Barudžija, T., Malenović, A., Petrović, L.,& Đekić, L.. (2022). Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije., 72(1), 36-60.
https://doi.org/10.5937/arhfarm72-35133

Ćirić A, Milinković Budinčić J, Medarević Đ, Dobričić V, Rmandić M, Barudžija T, Malenović A, Petrović L, Đekić L. Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen. in Arhiv za farmaciju. 2022;72(1):36-60.
doi:10.5937/arhfarm72-35133 .

Ćirić, Ana, Milinković Budinčić, Jelena, Medarević, Đorđe, Dobričić, Vladimir, Rmandić, Milena, Barudžija, Tanja, Malenović, Anđelija, Petrović, Lidija, Đekić, Ljiljana, "Influence of spray-drying process on properties of chitosan/xanthan gum polyelectrolyte complexes as carriers for oral delivery of ibuprofen" in Arhiv za farmaciju, 72, no. 1 (2022):36-60,
https://doi.org/10.5937/arhfarm72-35133 . .

TY  - JOUR
AU  - Rmandić, Milena
AU  - Stajić, Ana
AU  - Jančić, Jasna
AU  - Samardžić, Janko
AU  - Jović, Nebojša
AU  - Malenović, Anđelija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4262
AB  - In this research, a UHPLC–MS/MS method was developed and validated for the deter-
mination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of
zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by
monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using
Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 μm particle size) column with mobile phase com-
prising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min,
the column temperature was 30 ◦C and the injection volume was 3 μL. Desolvation temperature,
desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart
software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS
areas were determined by the image processing tool. The influence of hematocrit values (20–60%)
on accuracy and precision was evaluated to determine the range within which method for DBSs is
free from Hct or dependency is within acceptable limits. The validated method was applied to the
determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its
suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was
estimated by correlating its DPS and DBS levels.
PB  - MDPI
T2  - Molecules
T1  - Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice
VL  - 27
IS  - 15
DO  - 10.3390/molecules27154899
ER  - 

@article{
author = "Rmandić, Milena and Stajić, Ana and Jančić, Jasna and Samardžić, Janko and Jović, Nebojša and Malenović, Anđelija",
year = "2022",
abstract = "In this research, a UHPLC–MS/MS method was developed and validated for the deter-
mination of zonisamide in dried plasma spots (DPS) and dried blood spots (DBS). Detection of
zonisamide and internal standard, 1-(2,3-dichlorphenyl)piperazine, was carried out in ESI+ mode by
monitoring two MRM transitions per analyte. Total run time, less than 2.5 min, was achieved using
Acquity UPLC BEH Amide (2.1 × 100 mm, 1.7 μm particle size) column with mobile phase com-
prising acetonitrile–water (85:15%, v/v) with 0.075% formic acid. The flow rate was 0.225 mL/min,
the column temperature was 30 ◦C and the injection volume was 3 μL. Desolvation temperature,
desolvation gas flow rate, ion source temperature and cone gas flow rate were set by the IntelliStart
software tool in combination with tuning. All of the Guthrie cards were scanned, and DPS/DBS
areas were determined by the image processing tool. The influence of hematocrit values (20–60%)
on accuracy and precision was evaluated to determine the range within which method for DBSs is
free from Hct or dependency is within acceptable limits. The validated method was applied to the
determination of zonisamide levels in DPS and DBS samples obtained from patients confirming its
suitability for clinical application. Finally, the distribution of zonisamide into the red blood cells was
estimated by correlating its DPS and DBS levels.",
publisher = "MDPI",
journal = "Molecules",
title = "Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice",
volume = "27",
number = "15",
doi = "10.3390/molecules27154899"
}

Rmandić, M., Stajić, A., Jančić, J., Samardžić, J., Jović, N.,& Malenović, A.. (2022). Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice. in Molecules
MDPI., 27(15).
https://doi.org/10.3390/molecules27154899

Rmandić M, Stajić A, Jančić J, Samardžić J, Jović N, Malenović A. Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice. in Molecules. 2022;27(15).
doi:10.3390/molecules27154899 .

Rmandić, Milena, Stajić, Ana, Jančić, Jasna, Samardžić, Janko, Jović, Nebojša, Malenović, Anđelija, "Quantification of Zonisamide in Dried Blood Spots and Dried Plasma Spots by UPLC–MS/MS: Application to Clinical Practice" in Molecules, 27, no. 15 (2022),
https://doi.org/10.3390/molecules27154899 . .

TY  - JOUR
AU  - Đajić, Nevena
AU  - Krmar, Jovana
AU  - Rmandić, Milena
AU  - Rašević, Marija
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Malenović, Anđelija
AU  - Protić, Ana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4995
AB  - Most commonly used analytical technique for determination of active pharmaceutical ingredients and their impurities in quality control throughout all phases of drug research, development and manufacture is definitely reversed-phase high performance liquid chromatography (RP-HPLC). However, pharmaceutical industry professionals are often faced with various challenges in RP mode, which cannot be resolved with common variations in the composition of the mobile phase. These challenges often occur when analyzing compounds that contain basic ionizable groups, possess large differences in polarities and require consumption of high amounts of toxic organic solvents. Among available strategies for addressing the aforementioned issues, the most convenient one includes RP-HPLC mobile phase modifications by an addition of the proper chemical compounds. In that respect, RP-HPLC method can be easily adapted to the needs of the analysis without time-consuming and expensive equipment procurement. In this review the chaotropic chromatography, micellar liquid chromatography, and cyclodextrin modified RP-HPLC systems are presented and discussed in details. Special attention is devoted to the theoretical background, the possibility of retention modeling and applications in various fields of pharmacy, as well as their prospective in further research.
PB  - Elsevier B.V.
T2  - Journal of Chromatography Open
T1  - Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography
VL  - 2
DO  - 10.1016/j.jcoa.2021.100023
ER  - 

@article{
author = "Đajić, Nevena and Krmar, Jovana and Rmandić, Milena and Rašević, Marija and Otašević, Biljana and Zečević, Mira and Malenović, Anđelija and Protić, Ana",
year = "2022",
abstract = "Most commonly used analytical technique for determination of active pharmaceutical ingredients and their impurities in quality control throughout all phases of drug research, development and manufacture is definitely reversed-phase high performance liquid chromatography (RP-HPLC). However, pharmaceutical industry professionals are often faced with various challenges in RP mode, which cannot be resolved with common variations in the composition of the mobile phase. These challenges often occur when analyzing compounds that contain basic ionizable groups, possess large differences in polarities and require consumption of high amounts of toxic organic solvents. Among available strategies for addressing the aforementioned issues, the most convenient one includes RP-HPLC mobile phase modifications by an addition of the proper chemical compounds. In that respect, RP-HPLC method can be easily adapted to the needs of the analysis without time-consuming and expensive equipment procurement. In this review the chaotropic chromatography, micellar liquid chromatography, and cyclodextrin modified RP-HPLC systems are presented and discussed in details. Special attention is devoted to the theoretical background, the possibility of retention modeling and applications in various fields of pharmacy, as well as their prospective in further research.",
publisher = "Elsevier B.V.",
journal = "Journal of Chromatography Open",
title = "Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography",
volume = "2",
doi = "10.1016/j.jcoa.2021.100023"
}

Đajić, N., Krmar, J., Rmandić, M., Rašević, M., Otašević, B., Zečević, M., Malenović, A.,& Protić, A.. (2022). Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography. in Journal of Chromatography Open
Elsevier B.V.., 2.
https://doi.org/10.1016/j.jcoa.2021.100023

Đajić N, Krmar J, Rmandić M, Rašević M, Otašević B, Zečević M, Malenović A, Protić A. Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography. in Journal of Chromatography Open. 2022;2.
doi:10.1016/j.jcoa.2021.100023 .

Đajić, Nevena, Krmar, Jovana, Rmandić, Milena, Rašević, Marija, Otašević, Biljana, Zečević, Mira, Malenović, Anđelija, Protić, Ana, "Modified aqueous mobile phases: A way to improve retention behavior of active pharmaceutical compounds and their impurities in liquid chromatography" in Journal of Chromatography Open, 2 (2022),
https://doi.org/10.1016/j.jcoa.2021.100023 . .

TY  - JOUR
AU  - Koravović, Mladen
AU  - Marković, Bojan
AU  - Kovačević, Milena
AU  - Rmandić, Milena
AU  - Tasić, Gordana
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4296
AB  - The traditional concept of drug discovery is based on the occupancydriven pharmacology model. It implies the development of inhibitors occupying binding sites that directly affect protein functions. Therefore, proteins that do not have such binding sites are generally considered as pharmacologically intractable. Furthermore, drugs that act in this way must be administered in dosage regimens that often result in high systemic drug exposures in order to maintain sufficient protein inhibition. Thus, there is a risk of the onset of off-target binding and side effects. The landscape of drug discovery has been markedly changed since proteolysis targeting chimera (PROTAC) molecules emerged twenty years ago as a part of the event-driven pharmacology model. These are bifunctional molecules that harness the ubiquitin-proteasome system, and are composed of a ligand that binds the protein of interest (POI), a ligand that recruits E3 ubiquitin ligase (E3UL) and a linker that connects these two parts. Pharmacologically, PROTACs bring POI and E3UL into close proximity, which triggers the formation of a functional ternary complex POI-PROTAC-E3UL. This event drives polyubiquitination and subsequent POI degradation by the 26S proteasome. The development and exceptional properties of PROTAC molecules that brought them to clinical studies will be discussed in this paper. © 2022 Serbian Chemical Society. All rights reserved.
AB  - Традиционални концепт открића лекова базиран је на фармаколошком моделу заснованом на окупираности циљних протеина. То подразумева развој инхибитора који окупирају везујућа места директно повезана са функцијама протеина. Стога, протеини који немају таква везујућа места се генерално сматрају фармаколошки недодирљивим. Осим тога, лекови који делују на овакав начин морају се примењивати у режимима дозирања који често доводе до претеране системске изложености леку ради одржања довољне инхибиције протеина. Дакле, постоји ризик од појаве везивања лека ван свог примарног места дејства и нежељених ефеката. Окосница развоја лекова је значајно измењена откако су се појавили PROTAC (енг. proteolysis targeting chimera) молекули пре двадесет година као део фармаколошког модела заснованог на покретању догађаја који доводе до разградње циљних протеина. Ово су бифункционални молекули који користе убиквитин-протеазом систем, а састоје се од лиганда који се везује за протеин од инте- реса (POI), лиганда који регрутује Е3 убиквитин лигазу (E3UL) и линкера који повезује ова два дела. Фармаколошки, PROTAC молекули доводе POI и Е3UL у близину, што води формирању функционалног тернарног комплекса POI–PROTAC–Е3UL. Овај догађај води полиубиквитинацији и следственој деградацији POI 26S протеазомом. Развој и изу- зетна својства PROTAC молекула која су их довела до клиничких студија дискутовани су овом раду.
PB  - Serbian Chemical Society
T2  - Journal of the Serbian Chemical Society
T1  - Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy
T1  - Деградација протеина индукована PROTAC молекулима као нова стратегија у развоју лекова
VL  - 87
IS  - 7-8
SP  - 785
EP  - 811
DO  - 10.2298/JSC211209027K
ER  - 

@article{
author = "Koravović, Mladen and Marković, Bojan and Kovačević, Milena and Rmandić, Milena and Tasić, Gordana",
year = "2022",
abstract = "The traditional concept of drug discovery is based on the occupancydriven pharmacology model. It implies the development of inhibitors occupying binding sites that directly affect protein functions. Therefore, proteins that do not have such binding sites are generally considered as pharmacologically intractable. Furthermore, drugs that act in this way must be administered in dosage regimens that often result in high systemic drug exposures in order to maintain sufficient protein inhibition. Thus, there is a risk of the onset of off-target binding and side effects. The landscape of drug discovery has been markedly changed since proteolysis targeting chimera (PROTAC) molecules emerged twenty years ago as a part of the event-driven pharmacology model. These are bifunctional molecules that harness the ubiquitin-proteasome system, and are composed of a ligand that binds the protein of interest (POI), a ligand that recruits E3 ubiquitin ligase (E3UL) and a linker that connects these two parts. Pharmacologically, PROTACs bring POI and E3UL into close proximity, which triggers the formation of a functional ternary complex POI-PROTAC-E3UL. This event drives polyubiquitination and subsequent POI degradation by the 26S proteasome. The development and exceptional properties of PROTAC molecules that brought them to clinical studies will be discussed in this paper. © 2022 Serbian Chemical Society. All rights reserved., Традиционални концепт открића лекова базиран је на фармаколошком моделу заснованом на окупираности циљних протеина. То подразумева развој инхибитора који окупирају везујућа места директно повезана са функцијама протеина. Стога, протеини који немају таква везујућа места се генерално сматрају фармаколошки недодирљивим. Осим тога, лекови који делују на овакав начин морају се примењивати у режимима дозирања који често доводе до претеране системске изложености леку ради одржања довољне инхибиције протеина. Дакле, постоји ризик од појаве везивања лека ван свог примарног места дејства и нежељених ефеката. Окосница развоја лекова је значајно измењена откако су се појавили PROTAC (енг. proteolysis targeting chimera) молекули пре двадесет година као део фармаколошког модела заснованог на покретању догађаја који доводе до разградње циљних протеина. Ово су бифункционални молекули који користе убиквитин-протеазом систем, а састоје се од лиганда који се везује за протеин од инте- реса (POI), лиганда који регрутује Е3 убиквитин лигазу (E3UL) и линкера који повезује ова два дела. Фармаколошки, PROTAC молекули доводе POI и Е3UL у близину, што води формирању функционалног тернарног комплекса POI–PROTAC–Е3UL. Овај догађај води полиубиквитинацији и следственој деградацији POI 26S протеазомом. Развој и изу- зетна својства PROTAC молекула која су их довела до клиничких студија дискутовани су овом раду.",
publisher = "Serbian Chemical Society",
journal = "Journal of the Serbian Chemical Society",
title = "Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy, Деградација протеина индукована PROTAC молекулима као нова стратегија у развоју лекова",
volume = "87",
number = "7-8",
pages = "785-811",
doi = "10.2298/JSC211209027K"
}

Koravović, M., Marković, B., Kovačević, M., Rmandić, M.,& Tasić, G.. (2022). Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy. in Journal of the Serbian Chemical Society
Serbian Chemical Society., 87(7-8), 785-811.
https://doi.org/10.2298/JSC211209027K

Koravović M, Marković B, Kovačević M, Rmandić M, Tasić G. Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy. in Journal of the Serbian Chemical Society. 2022;87(7-8):785-811.
doi:10.2298/JSC211209027K .

Koravović, Mladen, Marković, Bojan, Kovačević, Milena, Rmandić, Milena, Tasić, Gordana, "Protein degradation induced by PROTAC molecules as an emerging drug discovery strategy" in Journal of the Serbian Chemical Society, 87, no. 7-8 (2022):785-811,
https://doi.org/10.2298/JSC211209027K . .

TY  - JOUR
AU  - Ćirić, Ana
AU  - Medarević, Đorđe
AU  - Čalija, Bojan
AU  - Dobričić, Vladimir
AU  - Rmandić, Milena
AU  - Barudžija, Tanja
AU  - Malenović, Anđelija
AU  - Đekić, Ljiljana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3759
AB  - The effect of the entrapment procedure of a poorly water soluble drug (ibuprofen) on physicochemical and drug release performances of chitosan/xanthan polyelectrolyte complexes (PECs) was investigated to achieve controlled drug release as the ultimate goal. The formation of PECs for two drug entrapment procedures (before or after the mixing of polymers) at pH 4.6 and 5.6 and three chitosan-to-xanthan mass ratios (1:1, 1:2 and 1:3) was observed by continuous decrease in conductivity during the PECs formation and increased apparent viscosity and hysteresis values. The most extensive crosslinking was observed with ibuprofen added before the PECs formation at pH 4.6 and chitosan-to-xanthan mass ratio 1:1. The PECs prepared at polymers' mass ratios 1:2 and 1:3 had higher yield and drug entrapment efficiency. DSC and FT-IR analysis confirmed ibuprofen entrapment in PECs and the partial disruption of its crystallinity. All ibuprofen release profiles were similar, with 60–70% of drug released after 12 h, mainly by diffusion, but erosion and polymer chain relaxation were also included. Potentially optimal can be considered the PEC prepared at pH 4.6, ibuprofen entrapped before the mixing of polymers at chitosan-to-xanthan mass ratio 1:2, which provided controlled drug release by zero-order kinetics, high yield, and drug entrapment efficiency.
PB  - Elsevier B.V.
T2  - International Journal of Biological Macromolecules
T1  - Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes
VL  - 167
SP  - 547
EP  - 558
DO  - 10.1016/j.ijbiomac.2020.11.201
ER  - 

@article{
author = "Ćirić, Ana and Medarević, Đorđe and Čalija, Bojan and Dobričić, Vladimir and Rmandić, Milena and Barudžija, Tanja and Malenović, Anđelija and Đekić, Ljiljana",
year = "2021",
abstract = "The effect of the entrapment procedure of a poorly water soluble drug (ibuprofen) on physicochemical and drug release performances of chitosan/xanthan polyelectrolyte complexes (PECs) was investigated to achieve controlled drug release as the ultimate goal. The formation of PECs for two drug entrapment procedures (before or after the mixing of polymers) at pH 4.6 and 5.6 and three chitosan-to-xanthan mass ratios (1:1, 1:2 and 1:3) was observed by continuous decrease in conductivity during the PECs formation and increased apparent viscosity and hysteresis values. The most extensive crosslinking was observed with ibuprofen added before the PECs formation at pH 4.6 and chitosan-to-xanthan mass ratio 1:1. The PECs prepared at polymers' mass ratios 1:2 and 1:3 had higher yield and drug entrapment efficiency. DSC and FT-IR analysis confirmed ibuprofen entrapment in PECs and the partial disruption of its crystallinity. All ibuprofen release profiles were similar, with 60–70% of drug released after 12 h, mainly by diffusion, but erosion and polymer chain relaxation were also included. Potentially optimal can be considered the PEC prepared at pH 4.6, ibuprofen entrapped before the mixing of polymers at chitosan-to-xanthan mass ratio 1:2, which provided controlled drug release by zero-order kinetics, high yield, and drug entrapment efficiency.",
publisher = "Elsevier B.V.",
journal = "International Journal of Biological Macromolecules",
title = "Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes",
volume = "167",
pages = "547-558",
doi = "10.1016/j.ijbiomac.2020.11.201"
}

Ćirić, A., Medarević, Đ., Čalija, B., Dobričić, V., Rmandić, M., Barudžija, T., Malenović, A.,& Đekić, L.. (2021). Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes. in International Journal of Biological Macromolecules
Elsevier B.V.., 167, 547-558.
https://doi.org/10.1016/j.ijbiomac.2020.11.201

Ćirić A, Medarević Đ, Čalija B, Dobričić V, Rmandić M, Barudžija T, Malenović A, Đekić L. Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes. in International Journal of Biological Macromolecules. 2021;167:547-558.
doi:10.1016/j.ijbiomac.2020.11.201 .

Ćirić, Ana, Medarević, Đorđe, Čalija, Bojan, Dobričić, Vladimir, Rmandić, Milena, Barudžija, Tanja, Malenović, Anđelija, Đekić, Ljiljana, "Effect of ibuprofen entrapment procedure on physicochemical and controlled drug release performances of chitosan/xanthan gum polyelectrolyte complexes" in International Journal of Biological Macromolecules, 167 (2021):547-558,
https://doi.org/10.1016/j.ijbiomac.2020.11.201 . .

TY  - JOUR
AU  - Rmandić, Milena
AU  - Rađenović, Miloš
AU  - Stanković, Jovana
AU  - Protić, Ana
AU  - Otašević, Biljana
AU  - Malenović, Anđelija
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4897
AB  - In this research, Analytical Quality by Design (AQbD) methodology was used to develop
the HILIC-PDA-CAD method for the determination of magnesium, pyridoxine and thiamine
content in a dietary supplement. Experiments were conducted on the Dionex Ulitimate 3000
HPLC system with PDA and CAD detectors. Separations were performed on the ZIC-HILIC
PEEK column (100 × 4.6 mm, 5 μm) with a mixture of acetonitrile, acetone and ammonium
acetate/ammonium formate aqueous solution (48:12:40, v/v/v) as the mobile phase. The detection
was performed at 220 nm. The optimal settings of CAD were defined with the one-factor-at-atime
approach: evaporation temperature 50°C, filter constant 10 s, pressure gas 60 psi. The
influence of qualitative (salt type) and quantitative factors (pH and salt concentration) on the
magnesium retention factor, kMg and the selectivity factor between pyridoxine and chloride anion,
αB6/Cl
-, was tested using the I-optimal design. The design space was defined by Monte Carlo
simulations and model coefficients’ errors were propagated with the aim of identifying the
conditions that meet the following criteria: kMg<4 and αB6/Cl
->3.5, with the probability π=95%.
From the derived 2D-Design Space graph, 95 mM of ammonium formate pH 4.4 was selected as
the optimal composition of the aqueous phase. The method was validated and its reliability in
routine application was confirmed.
AB  - U ovom istraživanju korišćena je metodologija ugradnje kvaliteta u metodu (AQbD) u cilju
razvoja HPLC-PDA-CAD metode za određivanje magnezijuma, pirodoksina i tiamina u
dijetetskom suplementu. Eksperimenti su izvedeni na Dionex Ulitimate 3000 HPLC sistemu sa
PDA i CAD detektorima. Razdvajanje je vršeno izokratskim eluiranjem mobilnom fazom koja je
smeša acetonitrila, acetona i vodenog rastvora amonijum acetata/amonijum formijata (48:12:40,
V/V/V) na ZIC-HILIC PEEK koloni (100 × 4.6 mm, 5 μm). Talasna dužina detekcije bila je 220
nm. Optimalna podešavanja CAD su definisana jednofaktorskim pristupom i obuhvaju:
temperaturu isparavanja 50°C, filter konstantu 10 s, pritisak gasa 60 psi. Uticaj kvalitativnih (vrsta
soli) i kvantitativnih faktora (pH vrednost i koncentracija soli) na retencioni faktor magnezijuma
(kMg) i faktor selektivnosti piridoksina i hloridnog anjona (αB6/Cl
-) ispitan je primenom Ioptimizacionog
dizajna. Prostor dizajna je definisan Monte Karlo simulacijom i propagiranjem
greške koeficijenata dobijenih matematičkih modela sa ciljem definisanja hromatografskih uslova
kod kojih su zadovoljeni sledeći kriterijumi: kMg<4 i αB6/Cl
->3,5, sa verovatnoćom π=95%. Iz
dobijenog 2D-grafika prostora dizajna izabran je optimalni sastav vodene faze koji je obuhvatao
95 mM amonijum formijat čija je pH vrednost podešena na 4,4. Metoda je validirana i dokazana
je njena pouzdanost u rutinskoj primeni.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - PDA-CAD method for the determination of magnesium, pyridoxine and thiamine in a dietary supplement supported by analytical quality by design methodology
VL  - 71
IS  - 5
SP  - 378
EP  - 392
DO  - 10.5937/arhfarm71‐32093
ER  - 

@article{
author = "Rmandić, Milena and Rađenović, Miloš and Stanković, Jovana and Protić, Ana and Otašević, Biljana and Malenović, Anđelija",
year = "2021",
abstract = "In this research, Analytical Quality by Design (AQbD) methodology was used to develop
the HILIC-PDA-CAD method for the determination of magnesium, pyridoxine and thiamine
content in a dietary supplement. Experiments were conducted on the Dionex Ulitimate 3000
HPLC system with PDA and CAD detectors. Separations were performed on the ZIC-HILIC
PEEK column (100 × 4.6 mm, 5 μm) with a mixture of acetonitrile, acetone and ammonium
acetate/ammonium formate aqueous solution (48:12:40, v/v/v) as the mobile phase. The detection
was performed at 220 nm. The optimal settings of CAD were defined with the one-factor-at-atime
approach: evaporation temperature 50°C, filter constant 10 s, pressure gas 60 psi. The
influence of qualitative (salt type) and quantitative factors (pH and salt concentration) on the
magnesium retention factor, kMg and the selectivity factor between pyridoxine and chloride anion,
αB6/Cl
-, was tested using the I-optimal design. The design space was defined by Monte Carlo
simulations and model coefficients’ errors were propagated with the aim of identifying the
conditions that meet the following criteria: kMg<4 and αB6/Cl
->3.5, with the probability π=95%.
From the derived 2D-Design Space graph, 95 mM of ammonium formate pH 4.4 was selected as
the optimal composition of the aqueous phase. The method was validated and its reliability in
routine application was confirmed., U ovom istraživanju korišćena je metodologija ugradnje kvaliteta u metodu (AQbD) u cilju
razvoja HPLC-PDA-CAD metode za određivanje magnezijuma, pirodoksina i tiamina u
dijetetskom suplementu. Eksperimenti su izvedeni na Dionex Ulitimate 3000 HPLC sistemu sa
PDA i CAD detektorima. Razdvajanje je vršeno izokratskim eluiranjem mobilnom fazom koja je
smeša acetonitrila, acetona i vodenog rastvora amonijum acetata/amonijum formijata (48:12:40,
V/V/V) na ZIC-HILIC PEEK koloni (100 × 4.6 mm, 5 μm). Talasna dužina detekcije bila je 220
nm. Optimalna podešavanja CAD su definisana jednofaktorskim pristupom i obuhvaju:
temperaturu isparavanja 50°C, filter konstantu 10 s, pritisak gasa 60 psi. Uticaj kvalitativnih (vrsta
soli) i kvantitativnih faktora (pH vrednost i koncentracija soli) na retencioni faktor magnezijuma
(kMg) i faktor selektivnosti piridoksina i hloridnog anjona (αB6/Cl
-) ispitan je primenom Ioptimizacionog
dizajna. Prostor dizajna je definisan Monte Karlo simulacijom i propagiranjem
greške koeficijenata dobijenih matematičkih modela sa ciljem definisanja hromatografskih uslova
kod kojih su zadovoljeni sledeći kriterijumi: kMg<4 i αB6/Cl
->3,5, sa verovatnoćom π=95%. Iz
dobijenog 2D-grafika prostora dizajna izabran je optimalni sastav vodene faze koji je obuhvatao
95 mM amonijum formijat čija je pH vrednost podešena na 4,4. Metoda je validirana i dokazana
je njena pouzdanost u rutinskoj primeni.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "PDA-CAD method for the determination of magnesium, pyridoxine and thiamine in a dietary supplement supported by analytical quality by design methodology",
volume = "71",
number = "5",
pages = "378-392",
doi = "10.5937/arhfarm71‐32093"
}

Rmandić, M., Rađenović, M., Stanković, J., Protić, A., Otašević, B.,& Malenović, A.. (2021). PDA-CAD method for the determination of magnesium, pyridoxine and thiamine in a dietary supplement supported by analytical quality by design methodology. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 71(5), 378-392.
https://doi.org/10.5937/arhfarm71‐32093

Rmandić M, Rađenović M, Stanković J, Protić A, Otašević B, Malenović A. PDA-CAD method for the determination of magnesium, pyridoxine and thiamine in a dietary supplement supported by analytical quality by design methodology. in Arhiv za farmaciju. 2021;71(5):378-392.
doi:10.5937/arhfarm71‐32093 .

Rmandić, Milena, Rađenović, Miloš, Stanković, Jovana, Protić, Ana, Otašević, Biljana, Malenović, Anđelija, "PDA-CAD method for the determination of magnesium, pyridoxine and thiamine in a dietary supplement supported by analytical quality by design methodology" in Arhiv za farmaciju, 71, no. 5 (2021):378-392,
https://doi.org/10.5937/arhfarm71‐32093 . .

TY  - JOUR
AU  - Koravović, Mladen
AU  - Tasić, Gordana
AU  - Rmandić, Milena
AU  - Marković, Bojan
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3918
AB  - Traditional drug discovery strategies are usually focused on occupancy of binding sites that directly affect functions of proteins. Hence, proteins that lack such binding sites are generally considered pharmacologically intractable. Modulators of protein activity, especially inhibitors, must be applied in appropriate dosage regimens that often lead to high systemic drug exposures in  order  to  maintain  sufficient  protein  inhibition in  vivo.  Consequently,  there  is  a  risk  of undesirable off-target drug binding and side effects. Recently, PROteolysis TArgeting Chimera (PROTAC) technology has emerged as a new pharmacological modality that exploits PROTAC molecules for induced protein degradation. PROTAC molecule is a heterobifunctional structure consisting of a ligand that binds a protein of interest (POI), a ligand for recruiting an E3 ubiquitin ligase (an enzyme involved in the POI ubiquitination) and a linker that connects these two. After POI-PROTAC-E3 ubiquitin ligase ternary complex formation, the POI undergoes ubiquitination (an enzymatic post-translational modification in which ubiquitin is attached to the POI) and degradation.  By  merging  the  principles  of  photopharmacology  and  PROTAC  technology, photocontrollable PROTACs for spatiotemporal control of induced protein degradation have recently emerged. The main advantage of photocontrollable over conventional PROTACs is the possible prevention of off-target toxicity thanks to local photoactivation.
AB  - Tradicionalne strategije razvoja lekova su obično osvrnute na okupiranje vezujućih mesta koja direktno utiču na funkcije proteina. Stoga se proteini koji nemaju takva vezujuća mesta generalno smatraju farmakološki nedodirljivim. Modulatori aktivnosti proteina, naročito inhibitori, koriste se u režimima doziranja koji često dovode do preterane sistemske izloženosti leku, a sve u cilju održavanja dovoljne inhibicije proteina in vivo. Posledično, postoji rizik od neželjenog vezivanja leka van svog primarnog mesta dejstva i neželjenih efekata. Nedavno je predstavljena tehnologija dirigovane proteolize (PROteolysis TArgeting Chimera, PROTAC) kao novi farmakološki modalitet koji koristi PROTAC molekule za indukovanu degradaciju proteina. PROTAC molekuli su heterobifunkcionalne strukture sačinjene od liganda koji se vezuje za protein od interesa (POI), liganda za regrutovanje E3 ubikvitin ligaze (enzima uključenog u ubikvitinaciju POI) i linkera koji ih povezuje. Nakon formiranja ternarnog kompleksa POI-PROTAC-E3 ubikvitin ligaza, POI podleže ubikvitinaciji (enzimskoj post-translacionoj modifikaciji u kojoj se ubikvitin vezuje za POI) i degradaciji. Integrisanjem principa fotofarmakologije i PROTAC tehnologije, nedavno su nastali su fotokontrolisani PROTAC molekuli za prostorno-vremensku kontrolu indukovane degradacije proteina. Zahvaljujući lokalnoj fotoaktivaciji, glavna prednost fotokontrolisanih nad konvencionalnim PROTAC molekulima je moguća prevencija toksičnosti koja nastaje usled dejstva van primarnog biološkog targeta.
PB  - Beograd : Savez farmaceutskih udruženja Srbije
T2  - Arhiv za farmaciju
T1  - Photocontrollable PROTAC molecules – structure and mechanism of action
T1  - Fotokontrolisani PROTAC molekuli - struktura i mehanizam dejstva
VL  - 71
IS  - 3
SP  - 161
EP  - 176
DO  - 10.5937/arhfarm71‐30785
ER  - 

@article{
author = "Koravović, Mladen and Tasić, Gordana and Rmandić, Milena and Marković, Bojan",
year = "2021",
abstract = "Traditional drug discovery strategies are usually focused on occupancy of binding sites that directly affect functions of proteins. Hence, proteins that lack such binding sites are generally considered pharmacologically intractable. Modulators of protein activity, especially inhibitors, must be applied in appropriate dosage regimens that often lead to high systemic drug exposures in  order  to  maintain  sufficient  protein  inhibition in  vivo.  Consequently,  there  is  a  risk  of undesirable off-target drug binding and side effects. Recently, PROteolysis TArgeting Chimera (PROTAC) technology has emerged as a new pharmacological modality that exploits PROTAC molecules for induced protein degradation. PROTAC molecule is a heterobifunctional structure consisting of a ligand that binds a protein of interest (POI), a ligand for recruiting an E3 ubiquitin ligase (an enzyme involved in the POI ubiquitination) and a linker that connects these two. After POI-PROTAC-E3 ubiquitin ligase ternary complex formation, the POI undergoes ubiquitination (an enzymatic post-translational modification in which ubiquitin is attached to the POI) and degradation.  By  merging  the  principles  of  photopharmacology  and  PROTAC  technology, photocontrollable PROTACs for spatiotemporal control of induced protein degradation have recently emerged. The main advantage of photocontrollable over conventional PROTACs is the possible prevention of off-target toxicity thanks to local photoactivation., Tradicionalne strategije razvoja lekova su obično osvrnute na okupiranje vezujućih mesta koja direktno utiču na funkcije proteina. Stoga se proteini koji nemaju takva vezujuća mesta generalno smatraju farmakološki nedodirljivim. Modulatori aktivnosti proteina, naročito inhibitori, koriste se u režimima doziranja koji često dovode do preterane sistemske izloženosti leku, a sve u cilju održavanja dovoljne inhibicije proteina in vivo. Posledično, postoji rizik od neželjenog vezivanja leka van svog primarnog mesta dejstva i neželjenih efekata. Nedavno je predstavljena tehnologija dirigovane proteolize (PROteolysis TArgeting Chimera, PROTAC) kao novi farmakološki modalitet koji koristi PROTAC molekule za indukovanu degradaciju proteina. PROTAC molekuli su heterobifunkcionalne strukture sačinjene od liganda koji se vezuje za protein od interesa (POI), liganda za regrutovanje E3 ubikvitin ligaze (enzima uključenog u ubikvitinaciju POI) i linkera koji ih povezuje. Nakon formiranja ternarnog kompleksa POI-PROTAC-E3 ubikvitin ligaza, POI podleže ubikvitinaciji (enzimskoj post-translacionoj modifikaciji u kojoj se ubikvitin vezuje za POI) i degradaciji. Integrisanjem principa fotofarmakologije i PROTAC tehnologije, nedavno su nastali su fotokontrolisani PROTAC molekuli za prostorno-vremensku kontrolu indukovane degradacije proteina. Zahvaljujući lokalnoj fotoaktivaciji, glavna prednost fotokontrolisanih nad konvencionalnim PROTAC molekulima je moguća prevencija toksičnosti koja nastaje usled dejstva van primarnog biološkog targeta.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Photocontrollable PROTAC molecules – structure and mechanism of action, Fotokontrolisani PROTAC molekuli - struktura i mehanizam dejstva",
volume = "71",
number = "3",
pages = "161-176",
doi = "10.5937/arhfarm71‐30785"
}

Koravović, M., Tasić, G., Rmandić, M.,& Marković, B.. (2021). Photocontrollable PROTAC molecules – structure and mechanism of action. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 71(3), 161-176.
https://doi.org/10.5937/arhfarm71‐30785

Koravović M, Tasić G, Rmandić M, Marković B. Photocontrollable PROTAC molecules – structure and mechanism of action. in Arhiv za farmaciju. 2021;71(3):161-176.
doi:10.5937/arhfarm71‐30785 .

Koravović, Mladen, Tasić, Gordana, Rmandić, Milena, Marković, Bojan, "Photocontrollable PROTAC molecules – structure and mechanism of action" in Arhiv za farmaciju, 71, no. 3 (2021):161-176,
https://doi.org/10.5937/arhfarm71‐30785 . .

TY  - JOUR
AU  - Rmandić, Milena
AU  - Malenović, Anđelija
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3647
AB  - In this paper, development of robust and reliable chaotropic chromatography method for the determination of aripiprazole and its impurities, following Analytical Quality by Design principles is presented. The efficient baseline separation and accurate determination of aripiprazole and its four impurities from tablets were set as Analytical Target Profile. In line with it, the influence of Critical Method Parameters (acetonitrile content, concentration of perchloric acid in water phase, and column temperature) on predefined Critical Method Attributes (separation of the critical pair of peaks, retention of the first and last eluting peak) was investigated with aid of the Central Composite Design. Further on Design Space, where Critical Method Parameters meet predefined acceptance limits with a high level of probability (π ≥ 85%), was computed as a result of performed Monte Carlo simulations. A normal operating conditions corresponding to 34% of acetonitrile, 66% of 42.5 mM perchloric acid, and column temperature at 35°C were selected from created Design Space. Robustness testing of the quantitative performances of the developed method was conducted combining Plackett–Burman design with alias matrix approach. Through the additional validation testing, reliability of the developed method for the use in the routine practice was completely confirmed
PB  - Wiley-VCH Verlag
T2  - Journal of Separation Science
T1  - Chaotropic chromatography method development for the determination of aripiprazole and its impurities following analytical quality by design principles
VL  - 43
IS  - 16
SP  - 3242
EP  - 3250
DO  - 10.1002/jssc.201900985
ER  - 

@article{
author = "Rmandić, Milena and Malenović, Anđelija",
year = "2020",
abstract = "In this paper, development of robust and reliable chaotropic chromatography method for the determination of aripiprazole and its impurities, following Analytical Quality by Design principles is presented. The efficient baseline separation and accurate determination of aripiprazole and its four impurities from tablets were set as Analytical Target Profile. In line with it, the influence of Critical Method Parameters (acetonitrile content, concentration of perchloric acid in water phase, and column temperature) on predefined Critical Method Attributes (separation of the critical pair of peaks, retention of the first and last eluting peak) was investigated with aid of the Central Composite Design. Further on Design Space, where Critical Method Parameters meet predefined acceptance limits with a high level of probability (π ≥ 85%), was computed as a result of performed Monte Carlo simulations. A normal operating conditions corresponding to 34% of acetonitrile, 66% of 42.5 mM perchloric acid, and column temperature at 35°C were selected from created Design Space. Robustness testing of the quantitative performances of the developed method was conducted combining Plackett–Burman design with alias matrix approach. Through the additional validation testing, reliability of the developed method for the use in the routine practice was completely confirmed",
publisher = "Wiley-VCH Verlag",
journal = "Journal of Separation Science",
title = "Chaotropic chromatography method development for the determination of aripiprazole and its impurities following analytical quality by design principles",
volume = "43",
number = "16",
pages = "3242-3250",
doi = "10.1002/jssc.201900985"
}

Rmandić, M.,& Malenović, A.. (2020). Chaotropic chromatography method development for the determination of aripiprazole and its impurities following analytical quality by design principles. in Journal of Separation Science
Wiley-VCH Verlag., 43(16), 3242-3250.
https://doi.org/10.1002/jssc.201900985

Rmandić M, Malenović A. Chaotropic chromatography method development for the determination of aripiprazole and its impurities following analytical quality by design principles. in Journal of Separation Science. 2020;43(16):3242-3250.
doi:10.1002/jssc.201900985 .

Rmandić, Milena, Malenović, Anđelija, "Chaotropic chromatography method development for the determination of aripiprazole and its impurities following analytical quality by design principles" in Journal of Separation Science, 43, no. 16 (2020):3242-3250,
https://doi.org/10.1002/jssc.201900985 . .

TY  - CONF
AU  - Rmandić, Milena
AU  - Dotsikas, Yannis
AU  - Stajić, Ana
AU  - Malenović, Anđelija
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4703
PB  - MSBM
C3  - XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.
T1  - Development of UHPLC- MS/MS Bioanalytical Method for Determination of Zonisamide in the Samples Collected in the Form of Dried Plasma Spots
SP  - 46
EP  - 46
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4703
ER  - 

@conference{
author = "Rmandić, Milena and Dotsikas, Yannis and Stajić, Ana and Malenović, Anđelija",
year = "2019",
publisher = "MSBM",
journal = "XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.",
title = "Development of UHPLC- MS/MS Bioanalytical Method for Determination of Zonisamide in the Samples Collected in the Form of Dried Plasma Spots",
pages = "46-46",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4703"
}

Rmandić, M., Dotsikas, Y., Stajić, A.,& Malenović, A.. (2019). Development of UHPLC- MS/MS Bioanalytical Method for Determination of Zonisamide in the Samples Collected in the Form of Dried Plasma Spots. in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.
MSBM., 46-46.
https://hdl.handle.net/21.15107/rcub_farfar_4703

Rmandić M, Dotsikas Y, Stajić A, Malenović A. Development of UHPLC- MS/MS Bioanalytical Method for Determination of Zonisamide in the Samples Collected in the Form of Dried Plasma Spots. in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia.. 2019;:46-46.
https://hdl.handle.net/21.15107/rcub_farfar_4703 .

Rmandić, Milena, Dotsikas, Yannis, Stajić, Ana, Malenović, Anđelija, "Development of UHPLC- MS/MS Bioanalytical Method for Determination of Zonisamide in the Samples Collected in the Form of Dried Plasma Spots" in XIII Mass Spectrometry in Biotechnology and Medicine (MSBM). July 7-13, 2019, Dubrovnik, Croatia. (2019):46-46,
https://hdl.handle.net/21.15107/rcub_farfar_4703 .

TY  - CONF
AU  - Rmandić, Milena
AU  - Dotsikas, Yannis
AU  - Malenović, Anđelija
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4707
PB  - University of Milano-Bicocca
C3  - 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.
T1  - Setting up procedure for precise and accurate formation of DBS of uniform area via experimental design and image processing methodology
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4707
ER  - 

@conference{
author = "Rmandić, Milena and Dotsikas, Yannis and Malenović, Anđelija",
year = "2019",
publisher = "University of Milano-Bicocca",
journal = "48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.",
title = "Setting up procedure for precise and accurate formation of DBS of uniform area via experimental design and image processing methodology",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4707"
}

Rmandić, M., Dotsikas, Y.,& Malenović, A.. (2019). Setting up procedure for precise and accurate formation of DBS of uniform area via experimental design and image processing methodology. in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.
University of Milano-Bicocca..
https://hdl.handle.net/21.15107/rcub_farfar_4707

Rmandić M, Dotsikas Y, Malenović A. Setting up procedure for precise and accurate formation of DBS of uniform area via experimental design and image processing methodology. in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy.. 2019;.
https://hdl.handle.net/21.15107/rcub_farfar_4707 .

Rmandić, Milena, Dotsikas, Yannis, Malenović, Anđelija, "Setting up procedure for precise and accurate formation of DBS of uniform area via experimental design and image processing methodology" in 48th International Symposium on High-Performance Liquid Phase Separations and Related Techniques HPLC 2019, June 16-20, 2019, Milan, Italy. (2019),
https://hdl.handle.net/21.15107/rcub_farfar_4707 .

TY  - JOUR
AU  - Rmandić, Milena
AU  - Dotsikas, Yannis
AU  - Malenović, Anđelija
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3325
AB  - In the present study we aimed at reaching a procedure for control of factors that have a potential to contribute to bioanalytical method bias and consistent dried blood spot (DBS) formation. The most influencing factors were identified via experimental design and image processing methodology. The effects of five qualitative factors temperature of blood samples, type of pipettes, pipetting technique, age of blood samples and analysts were investigated by multilevel categorical D-optimal design. Due to well-known influence of hematocrit (Hct) level on rheological characteristic of blood samples, five responses were observed through the study (RSD22%Hct, RSD30%Hct, RSD39%Hct, RSD51%Hct, RSD62%Hct) for their ability to provide insights into influence of factor settings onto DBS areas consistency. The area of blood spots was determined by image processing after scanning DBS cards with four spot replicates, corresponding to particular combination of investigated factors, as defined by experimental plan. The qualitative linear mathematical models with added appropriate two-factor interactions were derived by the principle of backward elimination. It was concluded that %RSD value of DBS, for all investigated Hct levels, is completely independent of type of pipettes and age of blood samples, but can significantly be affected by blood sample temperature, pipetting technique and training of analyst. Therefore, the procedure for precise and accurate formation of DBS of uniform area, regardless the Hct value, implies samples at body/room temperature, reversed pipetting technique for rigorous delivery of a sample volume onto the card and a properly trained analyst for handling samples. Finally, a verification experiment was performed and the adequacy of the suggested procedure was confirmed. Identification of the factors affecting the consistency of DBS formation provided the evidence that this contribution to total assay bias can be successfully controlled and reduced.
PB  - Elsevier Science BV, Amsterdam
T2  - Microchemical Journal
T1  - Identification of the factors affecting the consistency of DBS formation via experimental design and image processing methodology
VL  - 145
SP  - 1003
EP  - 1010
DO  - 10.1016/j.microc.2018.12.016
ER  - 

@article{
author = "Rmandić, Milena and Dotsikas, Yannis and Malenović, Anđelija",
year = "2019",
abstract = "In the present study we aimed at reaching a procedure for control of factors that have a potential to contribute to bioanalytical method bias and consistent dried blood spot (DBS) formation. The most influencing factors were identified via experimental design and image processing methodology. The effects of five qualitative factors temperature of blood samples, type of pipettes, pipetting technique, age of blood samples and analysts were investigated by multilevel categorical D-optimal design. Due to well-known influence of hematocrit (Hct) level on rheological characteristic of blood samples, five responses were observed through the study (RSD22%Hct, RSD30%Hct, RSD39%Hct, RSD51%Hct, RSD62%Hct) for their ability to provide insights into influence of factor settings onto DBS areas consistency. The area of blood spots was determined by image processing after scanning DBS cards with four spot replicates, corresponding to particular combination of investigated factors, as defined by experimental plan. The qualitative linear mathematical models with added appropriate two-factor interactions were derived by the principle of backward elimination. It was concluded that %RSD value of DBS, for all investigated Hct levels, is completely independent of type of pipettes and age of blood samples, but can significantly be affected by blood sample temperature, pipetting technique and training of analyst. Therefore, the procedure for precise and accurate formation of DBS of uniform area, regardless the Hct value, implies samples at body/room temperature, reversed pipetting technique for rigorous delivery of a sample volume onto the card and a properly trained analyst for handling samples. Finally, a verification experiment was performed and the adequacy of the suggested procedure was confirmed. Identification of the factors affecting the consistency of DBS formation provided the evidence that this contribution to total assay bias can be successfully controlled and reduced.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Microchemical Journal",
title = "Identification of the factors affecting the consistency of DBS formation via experimental design and image processing methodology",
volume = "145",
pages = "1003-1010",
doi = "10.1016/j.microc.2018.12.016"
}

Rmandić, M., Dotsikas, Y.,& Malenović, A.. (2019). Identification of the factors affecting the consistency of DBS formation via experimental design and image processing methodology. in Microchemical Journal
Elsevier Science BV, Amsterdam., 145, 1003-1010.
https://doi.org/10.1016/j.microc.2018.12.016

Rmandić M, Dotsikas Y, Malenović A. Identification of the factors affecting the consistency of DBS formation via experimental design and image processing methodology. in Microchemical Journal. 2019;145:1003-1010.
doi:10.1016/j.microc.2018.12.016 .

Rmandić, Milena, Dotsikas, Yannis, Malenović, Anđelija, "Identification of the factors affecting the consistency of DBS formation via experimental design and image processing methodology" in Microchemical Journal, 145 (2019):1003-1010,
https://doi.org/10.1016/j.microc.2018.12.016 . .

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 . .