TY  - CONF
AU  - Otašević, Biljana
AU  - Đajić, Nevena
AU  - Golubović, Jelena
AU  - Krmar, Jovana
AU  - Protić, Ana
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4667
AB  - Qualitative and quantitative assessment of drug substances and drug dosage forms is of utmost
importance for the quality control in pharmaceutical industry. Among the analytical techniques
available, high performance liquid chromatography (HPLC) stands out due to its high efficiency and
robustness. But, HPLC is also characterized by high consumption of toxic organic solvents used both for
method development and routine analyses. These solvents could harmfully impact the environment
and human health. Therefore, various strategies are developing for attracting eco-friendly character to
HPLC. Recently introduced green chromatography concept is based on the 3R rule (Reduce – Replace –
Recycle) implying the HPLC method development governed by the decreased use of acetonitrile labeled
as the most commonly used HPLC solvent and its replacement with ethanol or acetone (1). However,
these greener alternatives are known for their high UV absorbtion cut-off values making them
unsuitable for common UV/VIS detection. As appropriate solvent compatible solution, the use of
Corona Charged Aerosol Detector (CAD) is proposed. CAD is recognized as a universal detector
providing persistent mass sensitive analyte response independent of chemical structure (no need for
UV/VIS chromofores or ionization ability). The detection principle involves the nebulization of
chromatographic mobile phase, the evaporation of aerosol droplets and finally the production of
charged analyte particles (2). Assuming that chromatographic behavior and CAD generated responses
of analytes could be affected by various mobile phase related factors and/or detector parameters
settings, design of experiments (DoE) supported HPLC-CAD method development was performed for
the analysis of antipsychotic drug risperidone in presence of its impurities. By carefully planning the
number and the order of performing experiments, DoE methodology enables investigation of
significance effects of multiple factor effects together with their factor interactions. Different
experimental settings involving variation of organic solvent type and content in range 15-25% (V/V),
mobile phase flow rate (0.50-1.00 mL min -1) and column temperature (25-50 °C) were examined in
accordance with Box-Behnken design and selectivity factor between adjacent peaks on the
chromatogram was measured. The optimal conditions were defined applying mucticriteria decision
making approach by means of Derringer desirability function evaluation. Optimal separations were
achieved using 20% (V/V) of ethanol in mobile phase flowing at 0.6 mL min -1 under 37.5 °C column
temperature, while in case of acetone, optimum comprised 17% (V/V) of organic modifier, 0.8 mL min -1
and 37.5 °C. Finally, eco-friendly character of both methods was rated by Green Analytical Procedure
Index, GAPI (3).
AB  - Kvalitativna i kvantitativna analiza farmaceutskih supstanci i doziranih oblika predstavlja
činioce od najvećeg značaja za kontrolu kvaliteta u farmaceutskoj industriji. Među dostupnim
analitičkim tehnikama, tečna hromatografija pod visokim pritiskom (HPLC) ističe se svojom visokom
efikasnošć u i robusnošću. Ali, HPLC takođe karakteriše velika potrošnja toksičnih organskih rastvarača
koji se koriste za razvoj metoda i za rutinsku analizu lekova. Ovi rastvarači mogu štetno uticati i na
životnu sredinu i na zdravlje ljudi. Zbog toga se razvijaju različite strategije za obezbeđivanje ekološki
prihvatljivog karaktera HPLC metode. Nedavno predstavljeni koncept zelene hromatografije zasnovan
je na pravilu 3 R (Smanji - Zameni - Recikliraj), što podrazumeva razvoj HPLC metode koji se rukovodi
smanjenom upotrebom acetonitrila kao najčešće korišć enog rastvarača i njegovu zamenu etanolom ili
acetonom (1). Međutim, ove zelenije alternative poznate su po visokim vrednostima za UV apsorpciju,
što ih čini neprikladnim za uobičajenu UV/VIS detekciju. Kao odgovarajuće rešenje kompatibilno sa
pomenutim rastvaračima, predlaže se upotreba detektora naelektrisanja u aerosolu (CAD). CAD je
prepoznat kao univerzalni detektor koji pruža postojan odgovor zavistan od mase analita, a nezavisan
od hemijske strukture (postojanje UV/VIS hromofora ili sposobnosti jonizacije). Princip CAD detekcije
uključuje raspršivanje hromatografske mobilne faze u vidu kapljica aerosola, njihovo isparavanje i
konačno naelektrisavanje dobijenih čestica analita (2). Pretpostavljajuć i da na hromatografsko
ponašanje i CAD generisane odgovore analita mogu uticati različiti faktori povezani sa mobilnom fazom
i/ili parametrima podešavanja detektora, izvršen je razvoj HPLC-CAD metode za analizu antipsihotika
risperidona u prisustvu njegovih nečistoća uz podršku metodologije dizajna eksperimenata (DoE).
Pažljivim planiranjem broja i redosleda izvođenja eksperimenata, DoE omoguć ava ispitivanje značaja
efekata više faktora istovremeno zajedno sa njihovim faktorskim interakcijama. Različite
eksperimentalne postavke koje uključuju varijacije tipa i sadržaja organskog rastvarača u opsegu 15-
25% (V/V), protok mobilne faze (0,50-1,00 mL min -1) i temperaturu kolone (25-50 °C) ispitivane su u
skladu sa Boks-Behnken-ovim dizajnom i faktor selektivnosti između susednih vrhova na
hromatogramu je praćen. Optimalni uslovi definisani su primenom pristupa mutikriterijumskog
odlučivanja baziranog na izračunavanju Derringer-ove funkcije poželjnosti. Optimalna separacija je
postignuta primenom 20% (V/V) etanola u mobilnoj fazi koja teče pri 0,6 mL min -1 i pri temperaturi
kolone od 37,5 °C, dok je u slučaju acetona optimum podrazumevao 17% (V/V) organskog
modifikatora, protok 0,8 mL min -1 i temperaturu 37,5 °C. Konačno, ekološki karakter obe metode
procenjen je na osnovu indeksa zelenih analitičkih procedura, GAPI (3).
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - New strategies in the development of ecologically friendly RP‐HPLC methods based on the charged aerosol detector
T1  - Nove strategije u razvoju ekološki prihvatljivih RP‐HPLC metoda primenom detektora naelektrisanja u aerosolu
VL  - 71
IS  - 5 suplement
SP  - S24
EP  - S25
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4667
ER  - 

@conference{
author = "Otašević, Biljana and Đajić, Nevena and Golubović, Jelena and Krmar, Jovana and Protić, Ana",
year = "2021",
abstract = "Qualitative and quantitative assessment of drug substances and drug dosage forms is of utmost
importance for the quality control in pharmaceutical industry. Among the analytical techniques
available, high performance liquid chromatography (HPLC) stands out due to its high efficiency and
robustness. But, HPLC is also characterized by high consumption of toxic organic solvents used both for
method development and routine analyses. These solvents could harmfully impact the environment
and human health. Therefore, various strategies are developing for attracting eco-friendly character to
HPLC. Recently introduced green chromatography concept is based on the 3R rule (Reduce – Replace –
Recycle) implying the HPLC method development governed by the decreased use of acetonitrile labeled
as the most commonly used HPLC solvent and its replacement with ethanol or acetone (1). However,
these greener alternatives are known for their high UV absorbtion cut-off values making them
unsuitable for common UV/VIS detection. As appropriate solvent compatible solution, the use of
Corona Charged Aerosol Detector (CAD) is proposed. CAD is recognized as a universal detector
providing persistent mass sensitive analyte response independent of chemical structure (no need for
UV/VIS chromofores or ionization ability). The detection principle involves the nebulization of
chromatographic mobile phase, the evaporation of aerosol droplets and finally the production of
charged analyte particles (2). Assuming that chromatographic behavior and CAD generated responses
of analytes could be affected by various mobile phase related factors and/or detector parameters
settings, design of experiments (DoE) supported HPLC-CAD method development was performed for
the analysis of antipsychotic drug risperidone in presence of its impurities. By carefully planning the
number and the order of performing experiments, DoE methodology enables investigation of
significance effects of multiple factor effects together with their factor interactions. Different
experimental settings involving variation of organic solvent type and content in range 15-25% (V/V),
mobile phase flow rate (0.50-1.00 mL min -1) and column temperature (25-50 °C) were examined in
accordance with Box-Behnken design and selectivity factor between adjacent peaks on the
chromatogram was measured. The optimal conditions were defined applying mucticriteria decision
making approach by means of Derringer desirability function evaluation. Optimal separations were
achieved using 20% (V/V) of ethanol in mobile phase flowing at 0.6 mL min -1 under 37.5 °C column
temperature, while in case of acetone, optimum comprised 17% (V/V) of organic modifier, 0.8 mL min -1
and 37.5 °C. Finally, eco-friendly character of both methods was rated by Green Analytical Procedure
Index, GAPI (3)., Kvalitativna i kvantitativna analiza farmaceutskih supstanci i doziranih oblika predstavlja
činioce od najvećeg značaja za kontrolu kvaliteta u farmaceutskoj industriji. Među dostupnim
analitičkim tehnikama, tečna hromatografija pod visokim pritiskom (HPLC) ističe se svojom visokom
efikasnošć u i robusnošću. Ali, HPLC takođe karakteriše velika potrošnja toksičnih organskih rastvarača
koji se koriste za razvoj metoda i za rutinsku analizu lekova. Ovi rastvarači mogu štetno uticati i na
životnu sredinu i na zdravlje ljudi. Zbog toga se razvijaju različite strategije za obezbeđivanje ekološki
prihvatljivog karaktera HPLC metode. Nedavno predstavljeni koncept zelene hromatografije zasnovan
je na pravilu 3 R (Smanji - Zameni - Recikliraj), što podrazumeva razvoj HPLC metode koji se rukovodi
smanjenom upotrebom acetonitrila kao najčešće korišć enog rastvarača i njegovu zamenu etanolom ili
acetonom (1). Međutim, ove zelenije alternative poznate su po visokim vrednostima za UV apsorpciju,
što ih čini neprikladnim za uobičajenu UV/VIS detekciju. Kao odgovarajuće rešenje kompatibilno sa
pomenutim rastvaračima, predlaže se upotreba detektora naelektrisanja u aerosolu (CAD). CAD je
prepoznat kao univerzalni detektor koji pruža postojan odgovor zavistan od mase analita, a nezavisan
od hemijske strukture (postojanje UV/VIS hromofora ili sposobnosti jonizacije). Princip CAD detekcije
uključuje raspršivanje hromatografske mobilne faze u vidu kapljica aerosola, njihovo isparavanje i
konačno naelektrisavanje dobijenih čestica analita (2). Pretpostavljajuć i da na hromatografsko
ponašanje i CAD generisane odgovore analita mogu uticati različiti faktori povezani sa mobilnom fazom
i/ili parametrima podešavanja detektora, izvršen je razvoj HPLC-CAD metode za analizu antipsihotika
risperidona u prisustvu njegovih nečistoća uz podršku metodologije dizajna eksperimenata (DoE).
Pažljivim planiranjem broja i redosleda izvođenja eksperimenata, DoE omoguć ava ispitivanje značaja
efekata više faktora istovremeno zajedno sa njihovim faktorskim interakcijama. Različite
eksperimentalne postavke koje uključuju varijacije tipa i sadržaja organskog rastvarača u opsegu 15-
25% (V/V), protok mobilne faze (0,50-1,00 mL min -1) i temperaturu kolone (25-50 °C) ispitivane su u
skladu sa Boks-Behnken-ovim dizajnom i faktor selektivnosti između susednih vrhova na
hromatogramu je praćen. Optimalni uslovi definisani su primenom pristupa mutikriterijumskog
odlučivanja baziranog na izračunavanju Derringer-ove funkcije poželjnosti. Optimalna separacija je
postignuta primenom 20% (V/V) etanola u mobilnoj fazi koja teče pri 0,6 mL min -1 i pri temperaturi
kolone od 37,5 °C, dok je u slučaju acetona optimum podrazumevao 17% (V/V) organskog
modifikatora, protok 0,8 mL min -1 i temperaturu 37,5 °C. Konačno, ekološki karakter obe metode
procenjen je na osnovu indeksa zelenih analitičkih procedura, GAPI (3).",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "New strategies in the development of ecologically friendly RP‐HPLC methods based on the charged aerosol detector, Nove strategije u razvoju ekološki prihvatljivih RP‐HPLC metoda primenom detektora naelektrisanja u aerosolu",
volume = "71",
number = "5 suplement",
pages = "S24-S25",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4667"
}

Otašević, B., Đajić, N., Golubović, J., Krmar, J.,& Protić, A.. (2021). New strategies in the development of ecologically friendly RP‐HPLC methods based on the charged aerosol detector. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 71(5 suplement), S24-S25.
https://hdl.handle.net/21.15107/rcub_farfar_4667

Otašević B, Đajić N, Golubović J, Krmar J, Protić A. New strategies in the development of ecologically friendly RP‐HPLC methods based on the charged aerosol detector. in Arhiv za farmaciju. 2021;71(5 suplement):S24-S25.
https://hdl.handle.net/21.15107/rcub_farfar_4667 .

Otašević, Biljana, Đajić, Nevena, Golubović, Jelena, Krmar, Jovana, Protić, Ana, "New strategies in the development of ecologically friendly RP‐HPLC methods based on the charged aerosol detector" in Arhiv za farmaciju, 71, no. 5 suplement (2021):S24-S25,
https://hdl.handle.net/21.15107/rcub_farfar_4667 .

TY  - JOUR
AU  - Maljurić, Nevena
AU  - Otašević, Biljana
AU  - Golubović, Jelena
AU  - Krmar, Jovana
AU  - Zečević, Mira
AU  - Protić, Ana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3512
AB  - Green analytical chemistry is primarily directed towards minimization of the amount of waste associated with either the sample preparation or analysis. Among different chromatographic methods, liquid chromatography is considered the least green, allowing for various possibilities for greening. Using green solvents such as ethanol or acetone in RP-HPLC, as an alternative to acetonitrile, is recently attracting an attention. Both ethanol and acetone are characterized with low toxicity, with certain drawbacks limiting their regular use in RP-HPLC. Ethanol has low eluotropic strength and causes high backpressures, while acetone shows high UV cut-off, making it unsuitable for UV/Vis detection. To overcome the existing problems, Corona Charged Aerosol Detector was employed for development of RP-HPLC methods for separation of risperidone and its structurally related impurities with either ethanol or acetone as organic modifier. The methods were optimized by experimental design methodology, while optimal conditions for separation were determined using Derringer's desirability function. Detailed assessment of 3D surface plots of Derringer's desirability function enabled selection of 0.6 mL min−1 flow rate and 20% (v/v) organic modifier content as optimal when using ethanol, while in case of acetone mobile phase flow rate was 0.8 mL min−1 and organic modifier content 17% (v/v). Methods were validated and their eco-friendly character was confirmed through Green Analytical Procedure Index (GAPI). Although both methods are ecologically acceptable, the main drawback is reflected in the fact that no recycling or another waste treatment method exist. In the end, acetone was prioritized over ethanol, due to lower health hazard and decreased amount of generated waste.
PB  - Elsevier
T2  - Microchemical Journal
T1  - A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities
VL  - 153
DO  - 10.1016/j.microc.2019.104394
ER  - 

@article{
author = "Maljurić, Nevena and Otašević, Biljana and Golubović, Jelena and Krmar, Jovana and Zečević, Mira and Protić, Ana",
year = "2020",
abstract = "Green analytical chemistry is primarily directed towards minimization of the amount of waste associated with either the sample preparation or analysis. Among different chromatographic methods, liquid chromatography is considered the least green, allowing for various possibilities for greening. Using green solvents such as ethanol or acetone in RP-HPLC, as an alternative to acetonitrile, is recently attracting an attention. Both ethanol and acetone are characterized with low toxicity, with certain drawbacks limiting their regular use in RP-HPLC. Ethanol has low eluotropic strength and causes high backpressures, while acetone shows high UV cut-off, making it unsuitable for UV/Vis detection. To overcome the existing problems, Corona Charged Aerosol Detector was employed for development of RP-HPLC methods for separation of risperidone and its structurally related impurities with either ethanol or acetone as organic modifier. The methods were optimized by experimental design methodology, while optimal conditions for separation were determined using Derringer's desirability function. Detailed assessment of 3D surface plots of Derringer's desirability function enabled selection of 0.6 mL min−1 flow rate and 20% (v/v) organic modifier content as optimal when using ethanol, while in case of acetone mobile phase flow rate was 0.8 mL min−1 and organic modifier content 17% (v/v). Methods were validated and their eco-friendly character was confirmed through Green Analytical Procedure Index (GAPI). Although both methods are ecologically acceptable, the main drawback is reflected in the fact that no recycling or another waste treatment method exist. In the end, acetone was prioritized over ethanol, due to lower health hazard and decreased amount of generated waste.",
publisher = "Elsevier",
journal = "Microchemical Journal",
title = "A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities",
volume = "153",
doi = "10.1016/j.microc.2019.104394"
}

Maljurić, N., Otašević, B., Golubović, J., Krmar, J., Zečević, M.,& Protić, A.. (2020). A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities. in Microchemical Journal
Elsevier., 153.
https://doi.org/10.1016/j.microc.2019.104394

Maljurić N, Otašević B, Golubović J, Krmar J, Zečević M, Protić A. A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities. in Microchemical Journal. 2020;153.
doi:10.1016/j.microc.2019.104394 .

Maljurić, Nevena, Otašević, Biljana, Golubović, Jelena, Krmar, Jovana, Zečević, Mira, Protić, Ana, "A new strategy for development of eco-friendly RP-HPLC method using Corona Charged Aerosol Detector and its application for simultaneous analysis of risperidone and its related impurities" in Microchemical Journal, 153 (2020),
https://doi.org/10.1016/j.microc.2019.104394 . .

TY  - JOUR
AU  - Ignjatović, Janko
AU  - Maljurić, Nevena
AU  - Golubović, Jelena
AU  - Ravnikar, Matjaž
AU  - Petković, Miloš
AU  - Savodnik, Nika
AU  - Štrukelj, Borut
AU  - Otašević, Biljana
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3661
AB  - Recently, growing interest is devoted to investigation of bioactive secondary metabolites of endophytic fungi. Thus, as an extension to our previous achievements related to antimicrobial potential of endophytic fungi, Phomopsis species isolated from  conifer  needles  was  selected  as  appropriately  promising  natural  source  for  drug  discovery.  Its  dichloromethane  and  ethanol  extracts  considerably  inhibited  growth  of  Escherichia  coli  and  Staphylococcus  aureus.  Moreover,  the  indi-vidual compounds of dichloromethane extract have been separated, collected and purified using semi preparative liquid chromatographic analysis and comprehensively characterized using mass spectrometry (MS) and nuclear magnetic res-onance spectroscopy (NMR). Based on their antimicrobial activity and unique structural characteristics in comparison with  well-established  drugs  from  the  same  therapeutic  category,  two  dominant  compounds  (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3-(3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate  (denoted  as  325-3)  and  (Z)-(Z)-2-acetoxyprop-1-en-1-yl  3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate  (denoted  as  325-5)  were  recognized  as  valuable  leading structures for future discovery of novel antibiotics.
PB  - Slovenian Chemical Society
T2  - Acta Chimica Slovenica
T1  - Characterization of biomolecules with antibiotic activity from endophytic fungi phomopsis species
VL  - 67
IS  - 2
SP  - 445
EP  - 461
DO  - 10.17344/acsi.2019.5389
ER  - 

@article{
author = "Ignjatović, Janko and Maljurić, Nevena and Golubović, Jelena and Ravnikar, Matjaž and Petković, Miloš and Savodnik, Nika and Štrukelj, Borut and Otašević, Biljana",
year = "2020",
abstract = "Recently, growing interest is devoted to investigation of bioactive secondary metabolites of endophytic fungi. Thus, as an extension to our previous achievements related to antimicrobial potential of endophytic fungi, Phomopsis species isolated from  conifer  needles  was  selected  as  appropriately  promising  natural  source  for  drug  discovery.  Its  dichloromethane  and  ethanol  extracts  considerably  inhibited  growth  of  Escherichia  coli  and  Staphylococcus  aureus.  Moreover,  the  indi-vidual compounds of dichloromethane extract have been separated, collected and purified using semi preparative liquid chromatographic analysis and comprehensively characterized using mass spectrometry (MS) and nuclear magnetic res-onance spectroscopy (NMR). Based on their antimicrobial activity and unique structural characteristics in comparison with  well-established  drugs  from  the  same  therapeutic  category,  two  dominant  compounds  (Z)-(Z)-2-acetoxyprop-1-en-1-yl-3-(3-((E)-3,4-dihydroxypent-1-en-1-yl)oxiran-2-yl)acrylate  (denoted  as  325-3)  and  (Z)-(Z)-2-acetoxyprop-1-en-1-yl  3-(3-((E)-4-hydroxy-3-oxopent-1-en-1-yl)oxiran-2-yl)acrylate  (denoted  as  325-5)  were  recognized  as  valuable  leading structures for future discovery of novel antibiotics.",
publisher = "Slovenian Chemical Society",
journal = "Acta Chimica Slovenica",
title = "Characterization of biomolecules with antibiotic activity from endophytic fungi phomopsis species",
volume = "67",
number = "2",
pages = "445-461",
doi = "10.17344/acsi.2019.5389"
}

Ignjatović, J., Maljurić, N., Golubović, J., Ravnikar, M., Petković, M., Savodnik, N., Štrukelj, B.,& Otašević, B.. (2020). Characterization of biomolecules with antibiotic activity from endophytic fungi phomopsis species. in Acta Chimica Slovenica
Slovenian Chemical Society., 67(2), 445-461.
https://doi.org/10.17344/acsi.2019.5389

Ignjatović J, Maljurić N, Golubović J, Ravnikar M, Petković M, Savodnik N, Štrukelj B, Otašević B. Characterization of biomolecules with antibiotic activity from endophytic fungi phomopsis species. in Acta Chimica Slovenica. 2020;67(2):445-461.
doi:10.17344/acsi.2019.5389 .

Ignjatović, Janko, Maljurić, Nevena, Golubović, Jelena, Ravnikar, Matjaž, Petković, Miloš, Savodnik, Nika, Štrukelj, Borut, Otašević, Biljana, "Characterization of biomolecules with antibiotic activity from endophytic fungi phomopsis species" in Acta Chimica Slovenica, 67, no. 2 (2020):445-461,
https://doi.org/10.17344/acsi.2019.5389 . .

TY  - JOUR
AU  - Maljurić, Nevena
AU  - Golubović, Jelena
AU  - Otašević, Biljana
AU  - Krmar, Jovana
AU  - Zečević, Mira
AU  - Protić, Ana
PY  - 2019
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3666
AB  - Cyclodextrins (CDs) are widely used in pharmaceutical analysis due to its biodegradability and eco-friendly character. The particular structure of CDs, characterized by hydrophobic cavity, enables the formation of inclusion complexes with variety of organic compounds. As structures lacking chromophores, CDs could not be detected by Photodiode Array (PDA) detector and Corona Charged Aerosol Detector (CAD) was introduced as the most appropriate detector for the formed complexes. The aim of the study was to investigate the degree of complexation between telmisartan, used as a model substance, and β-CD. Moreover, the effect of different β-CD concentrations (5-15 mM) and pH of the aqueous part of mobile phase (3-7) on the degree of complexation was also assessed. The intensity of the formed complex appeared to be the highest when 15 mM β-CD was used for the complexation. Also, it was noticed that the increase in peak areas with an increasing β-CD concentration was more evident at pH 7 in comparison with the same trend at lower pH values. The reproducibility of the measurement was confirmed by low relative standard deviation (RSD) of peak areas within five measurements. These findings support the use of HPLC-CAD methods for studying the process of inclusion complexes formation.
PB  - Pharmaceutical Association of Serbia
T2  - Arhiv za farmaciju
T1  - The potential of corona charged aerosol detector for investigation of telmisartan-β-cyclodextrin inclusion complexes
VL  - 69
IS  - 1
SP  - 1
EP  - 14
DO  - 10.5937/arhfarm1901001M
ER  - 

@article{
author = "Maljurić, Nevena and Golubović, Jelena and Otašević, Biljana and Krmar, Jovana and Zečević, Mira and Protić, Ana",
year = "2019",
abstract = "Cyclodextrins (CDs) are widely used in pharmaceutical analysis due to its biodegradability and eco-friendly character. The particular structure of CDs, characterized by hydrophobic cavity, enables the formation of inclusion complexes with variety of organic compounds. As structures lacking chromophores, CDs could not be detected by Photodiode Array (PDA) detector and Corona Charged Aerosol Detector (CAD) was introduced as the most appropriate detector for the formed complexes. The aim of the study was to investigate the degree of complexation between telmisartan, used as a model substance, and β-CD. Moreover, the effect of different β-CD concentrations (5-15 mM) and pH of the aqueous part of mobile phase (3-7) on the degree of complexation was also assessed. The intensity of the formed complex appeared to be the highest when 15 mM β-CD was used for the complexation. Also, it was noticed that the increase in peak areas with an increasing β-CD concentration was more evident at pH 7 in comparison with the same trend at lower pH values. The reproducibility of the measurement was confirmed by low relative standard deviation (RSD) of peak areas within five measurements. These findings support the use of HPLC-CAD methods for studying the process of inclusion complexes formation.",
publisher = "Pharmaceutical Association of Serbia",
journal = "Arhiv za farmaciju",
title = "The potential of corona charged aerosol detector for investigation of telmisartan-β-cyclodextrin inclusion complexes",
volume = "69",
number = "1",
pages = "1-14",
doi = "10.5937/arhfarm1901001M"
}

Maljurić, N., Golubović, J., Otašević, B., Krmar, J., Zečević, M.,& Protić, A.. (2019). The potential of corona charged aerosol detector for investigation of telmisartan-β-cyclodextrin inclusion complexes. in Arhiv za farmaciju
Pharmaceutical Association of Serbia., 69(1), 1-14.
https://doi.org/10.5937/arhfarm1901001M

Maljurić N, Golubović J, Otašević B, Krmar J, Zečević M, Protić A. The potential of corona charged aerosol detector for investigation of telmisartan-β-cyclodextrin inclusion complexes. in Arhiv za farmaciju. 2019;69(1):1-14.
doi:10.5937/arhfarm1901001M .

Maljurić, Nevena, Golubović, Jelena, Otašević, Biljana, Krmar, Jovana, Zečević, Mira, Protić, Ana, "The potential of corona charged aerosol detector for investigation of telmisartan-β-cyclodextrin inclusion complexes" in Arhiv za farmaciju, 69, no. 1 (2019):1-14,
https://doi.org/10.5937/arhfarm1901001M . .

TY  - JOUR
AU  - Maljurić, Nevena
AU  - Golubović, Jelena
AU  - Ravnikar, Matjaz
AU  - Zigon, Dušan
AU  - Štrukelj, Borut
AU  - Otašević, Biljana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3182
AB  - Diabetes mellitus is one of the leading world's public health problems. Therefore, it is of a huge interest to develop new antidiabetic drugs. Apart from traditional therapy of diabetes, nowadays, importance is given to natural substances with antidiabetic potential. Fomes fomentarius is a mushroom widely used for different purposes, due to its range of already confirmed activities. Fomentariol is a constituent of Fomes fomentarius, responsible for its antidiabetic potential. In that respect, it is important to develop a method for isolation and quantification of fomentariol from fungal material, which will be simple and efficient. Multistep, complex extraction applied in the previously reported studies was avoided with ethanol, providing rapid single-step extraction. The presence of fomentariol in ethanolic extract was confirmed by high-resolution mass spectrometry. Semipreparative HPLC method was developed and applied for isolation from ethanol extract and purification of the active compound fomentariol. It was a gradient reversed-phase method with a mobile phase consisting of acetonitrile and 0.1% formic acid in water and total run time of 15 minutes. The amount of 6.5 mg of high-purity fomentariol was determined by quantitative NMR with toluene as internal standard. The isolated and determined amount of substance can be further used for the quantitative estimation of activity of fomentariol.
PB  - Hindawi Ltd, London
T2  - Journal of Analytical Methods in Chemistry
T1  - Isolation and Determination of Fomentariol: Novel Potential Antidiabetic Drug from Fungal Material
DO  - 10.1155/2018/2434691
ER  - 

@article{
author = "Maljurić, Nevena and Golubović, Jelena and Ravnikar, Matjaz and Zigon, Dušan and Štrukelj, Borut and Otašević, Biljana",
year = "2018",
abstract = "Diabetes mellitus is one of the leading world's public health problems. Therefore, it is of a huge interest to develop new antidiabetic drugs. Apart from traditional therapy of diabetes, nowadays, importance is given to natural substances with antidiabetic potential. Fomes fomentarius is a mushroom widely used for different purposes, due to its range of already confirmed activities. Fomentariol is a constituent of Fomes fomentarius, responsible for its antidiabetic potential. In that respect, it is important to develop a method for isolation and quantification of fomentariol from fungal material, which will be simple and efficient. Multistep, complex extraction applied in the previously reported studies was avoided with ethanol, providing rapid single-step extraction. The presence of fomentariol in ethanolic extract was confirmed by high-resolution mass spectrometry. Semipreparative HPLC method was developed and applied for isolation from ethanol extract and purification of the active compound fomentariol. It was a gradient reversed-phase method with a mobile phase consisting of acetonitrile and 0.1% formic acid in water and total run time of 15 minutes. The amount of 6.5 mg of high-purity fomentariol was determined by quantitative NMR with toluene as internal standard. The isolated and determined amount of substance can be further used for the quantitative estimation of activity of fomentariol.",
publisher = "Hindawi Ltd, London",
journal = "Journal of Analytical Methods in Chemistry",
title = "Isolation and Determination of Fomentariol: Novel Potential Antidiabetic Drug from Fungal Material",
doi = "10.1155/2018/2434691"
}

Maljurić, N., Golubović, J., Ravnikar, M., Zigon, D., Štrukelj, B.,& Otašević, B.. (2018). Isolation and Determination of Fomentariol: Novel Potential Antidiabetic Drug from Fungal Material. in Journal of Analytical Methods in Chemistry
Hindawi Ltd, London..
https://doi.org/10.1155/2018/2434691

Maljurić N, Golubović J, Ravnikar M, Zigon D, Štrukelj B, Otašević B. Isolation and Determination of Fomentariol: Novel Potential Antidiabetic Drug from Fungal Material. in Journal of Analytical Methods in Chemistry. 2018;.
doi:10.1155/2018/2434691 .

Maljurić, Nevena, Golubović, Jelena, Ravnikar, Matjaz, Zigon, Dušan, Štrukelj, Borut, Otašević, Biljana, "Isolation and Determination of Fomentariol: Novel Potential Antidiabetic Drug from Fungal Material" in Journal of Analytical Methods in Chemistry (2018),
https://doi.org/10.1155/2018/2434691 . .

TY  - JOUR
AU  - Maljurić, Nevena
AU  - Golubović, Jelena
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Protić, Ana
PY  - 2018
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3174
AB  - Applying green chromatography methods is currently one of the challenges in liquid chromatography. Among different strategies, using cyclodextrin (CD) mobile phase modifiers was applied in this paper. CDs can form inclusion complexes with a wide variety of hydrophobic organic compounds and, consequently, affect their retention behavior. CD-containing mobile phases possess complicated complexation and adsorption equilibria so retention is dependent not only on chromatographic parameters and properties of the compound but also on properties of compound-CD complex. Docking study was used to calculate association constants of the selected antipsychotics (risperidone, olanzapine, and their impurities) and beta-CD complexes and predict which part of the molecule structure will most likely incorporate into the beta-CD cavity. Quantitative structure-retention relationship model (QSRR) for selected model substances was built employing artificial neural network (ANN) technique. Reliable QSRR model was obtained using molecular descriptors, complex association constants, and chromatographic factors. The multilayer perceptron network with 11-8-1 topology, trained with back propagation algorithm, showed the best performance. Root mean square error for training, validation, and test was 0.2954, 0.3633, and 0.4864, respectively. The correlation coefficient (R-2) between experimentally obtained retention factor values [k(exp)] and values computed or predicted by ANN [k(ANN)] was 0.9962 for training, 0.9927 for validation, and 0.9829 for test, indicating good predictive ability of the model. The optimized network was used for development of green chromatography method for separation of risperidone and its related impurities, as well as olanzapine and its related impurities in a relatively short run time and with low consumption of organic modifier. The developed methods were validated in accordance with ICH Q2 (R1) quideline and all parameters fulfilled the defined criteria. The greenness of the proposed methods has also been demonstrated.
PB  - Springer Heidelberg, Heidelberg
T2  - Analytical and Bioanalytical Chemistry
T1  - Quantitative structure -retention relationship modeling of selected antipsychotics and their impurities in green liquid chromatography using cyclodextrin mobile phases
VL  - 410
IS  - 10
SP  - 2533
EP  - 2550
DO  - 10.1007/s00216-018-0911-3
ER  - 

@article{
author = "Maljurić, Nevena and Golubović, Jelena and Otašević, Biljana and Zečević, Mira and Protić, Ana",
year = "2018",
abstract = "Applying green chromatography methods is currently one of the challenges in liquid chromatography. Among different strategies, using cyclodextrin (CD) mobile phase modifiers was applied in this paper. CDs can form inclusion complexes with a wide variety of hydrophobic organic compounds and, consequently, affect their retention behavior. CD-containing mobile phases possess complicated complexation and adsorption equilibria so retention is dependent not only on chromatographic parameters and properties of the compound but also on properties of compound-CD complex. Docking study was used to calculate association constants of the selected antipsychotics (risperidone, olanzapine, and their impurities) and beta-CD complexes and predict which part of the molecule structure will most likely incorporate into the beta-CD cavity. Quantitative structure-retention relationship model (QSRR) for selected model substances was built employing artificial neural network (ANN) technique. Reliable QSRR model was obtained using molecular descriptors, complex association constants, and chromatographic factors. The multilayer perceptron network with 11-8-1 topology, trained with back propagation algorithm, showed the best performance. Root mean square error for training, validation, and test was 0.2954, 0.3633, and 0.4864, respectively. The correlation coefficient (R-2) between experimentally obtained retention factor values [k(exp)] and values computed or predicted by ANN [k(ANN)] was 0.9962 for training, 0.9927 for validation, and 0.9829 for test, indicating good predictive ability of the model. The optimized network was used for development of green chromatography method for separation of risperidone and its related impurities, as well as olanzapine and its related impurities in a relatively short run time and with low consumption of organic modifier. The developed methods were validated in accordance with ICH Q2 (R1) quideline and all parameters fulfilled the defined criteria. The greenness of the proposed methods has also been demonstrated.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Analytical and Bioanalytical Chemistry",
title = "Quantitative structure -retention relationship modeling of selected antipsychotics and their impurities in green liquid chromatography using cyclodextrin mobile phases",
volume = "410",
number = "10",
pages = "2533-2550",
doi = "10.1007/s00216-018-0911-3"
}

Maljurić, N., Golubović, J., Otašević, B., Zečević, M.,& Protić, A.. (2018). Quantitative structure -retention relationship modeling of selected antipsychotics and their impurities in green liquid chromatography using cyclodextrin mobile phases. in Analytical and Bioanalytical Chemistry
Springer Heidelberg, Heidelberg., 410(10), 2533-2550.
https://doi.org/10.1007/s00216-018-0911-3

Maljurić N, Golubović J, Otašević B, Zečević M, Protić A. Quantitative structure -retention relationship modeling of selected antipsychotics and their impurities in green liquid chromatography using cyclodextrin mobile phases. in Analytical and Bioanalytical Chemistry. 2018;410(10):2533-2550.
doi:10.1007/s00216-018-0911-3 .

Maljurić, Nevena, Golubović, Jelena, Otašević, Biljana, Zečević, Mira, Protić, Ana, "Quantitative structure -retention relationship modeling of selected antipsychotics and their impurities in green liquid chromatography using cyclodextrin mobile phases" in Analytical and Bioanalytical Chemistry, 410, no. 10 (2018):2533-2550,
https://doi.org/10.1007/s00216-018-0911-3 . .

TY  - JOUR
AU  - Sljivić, Jasmina
AU  - Protić, Ana
AU  - Otašević, Biljana
AU  - Golubović, Jelena
AU  - Zečević, Mira
AU  - Krmar, Jovana
PY  - 2017
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2905
AB  - Multicriteria optimization methodology was applied in development of UHPLC-UV-MS method for separation of cilazapril, hydrochlorothiazide and their degradation products. This method is also applicable for analysis of cilazapril, hydrochlorothiazide and their degradation products in combined tablet formulation. Prior to method optimization forced degradation studies were conducted. Cilazapril and hydrochlorothiazide were subjected to acidic (0.1, 0.5 and 1.0M HCl), basic (0.1, 0.5 and 1.0M NaOH), thermal (70 degrees C), oxidative (3-30% H2O2) degradation and photodegradation (day light). Cilazapril appeared to be unstable toward acid and base and resulted in formation of cilazaprilat. Hydrochlorothiazide significantly degraded after acid, base and thermal hydrolysis and formed degradation product was 4-amino-6-chlorobenzene-1.3-disulfonamide. For both substances, after oxidative degradation unknown products have arisen. Initial percentage of acetonitrile in mobile phase, final percentage of acetonitrile in mobile phase, time of gradient elution and column temperature were defined as variables to be optimized toward two chromatographic responses by means of central composite design and Derringer's desirability function. The satisfactory chromatographic analysis was achieved on Kinetex C18 (2.6 mu m, 50 x 2.1 mm) column with temperature set at 25 degrees C. The final mobile phase consisted of acetonitrile and 20mM ammonium formate buffer (pH adjusted to 8.5). The flow rate of the mobile phase was 400 mu L min(-1) and it was pumped in a gradient elution mode.
PB  - Oxford Univ Press Inc, Cary
T2  - Journal of Chromatographic Science
T1  - Multicriteria Optimization Methodology in Stability-Indicating Method Development of Cilazapril and Hydrochlorothiazide
VL  - 55
IS  - 6
SP  - 625
EP  - 637
DO  - 10.1093/chromsci/bmx018
ER  - 

@article{
author = "Sljivić, Jasmina and Protić, Ana and Otašević, Biljana and Golubović, Jelena and Zečević, Mira and Krmar, Jovana",
year = "2017",
abstract = "Multicriteria optimization methodology was applied in development of UHPLC-UV-MS method for separation of cilazapril, hydrochlorothiazide and their degradation products. This method is also applicable for analysis of cilazapril, hydrochlorothiazide and their degradation products in combined tablet formulation. Prior to method optimization forced degradation studies were conducted. Cilazapril and hydrochlorothiazide were subjected to acidic (0.1, 0.5 and 1.0M HCl), basic (0.1, 0.5 and 1.0M NaOH), thermal (70 degrees C), oxidative (3-30% H2O2) degradation and photodegradation (day light). Cilazapril appeared to be unstable toward acid and base and resulted in formation of cilazaprilat. Hydrochlorothiazide significantly degraded after acid, base and thermal hydrolysis and formed degradation product was 4-amino-6-chlorobenzene-1.3-disulfonamide. For both substances, after oxidative degradation unknown products have arisen. Initial percentage of acetonitrile in mobile phase, final percentage of acetonitrile in mobile phase, time of gradient elution and column temperature were defined as variables to be optimized toward two chromatographic responses by means of central composite design and Derringer's desirability function. The satisfactory chromatographic analysis was achieved on Kinetex C18 (2.6 mu m, 50 x 2.1 mm) column with temperature set at 25 degrees C. The final mobile phase consisted of acetonitrile and 20mM ammonium formate buffer (pH adjusted to 8.5). The flow rate of the mobile phase was 400 mu L min(-1) and it was pumped in a gradient elution mode.",
publisher = "Oxford Univ Press Inc, Cary",
journal = "Journal of Chromatographic Science",
title = "Multicriteria Optimization Methodology in Stability-Indicating Method Development of Cilazapril and Hydrochlorothiazide",
volume = "55",
number = "6",
pages = "625-637",
doi = "10.1093/chromsci/bmx018"
}

Sljivić, J., Protić, A., Otašević, B., Golubović, J., Zečević, M.,& Krmar, J.. (2017). Multicriteria Optimization Methodology in Stability-Indicating Method Development of Cilazapril and Hydrochlorothiazide. in Journal of Chromatographic Science
Oxford Univ Press Inc, Cary., 55(6), 625-637.
https://doi.org/10.1093/chromsci/bmx018

Sljivić J, Protić A, Otašević B, Golubović J, Zečević M, Krmar J. Multicriteria Optimization Methodology in Stability-Indicating Method Development of Cilazapril and Hydrochlorothiazide. in Journal of Chromatographic Science. 2017;55(6):625-637.
doi:10.1093/chromsci/bmx018 .

Sljivić, Jasmina, Protić, Ana, Otašević, Biljana, Golubović, Jelena, Zečević, Mira, Krmar, Jovana, "Multicriteria Optimization Methodology in Stability-Indicating Method Development of Cilazapril and Hydrochlorothiazide" in Journal of Chromatographic Science, 55, no. 6 (2017):625-637,
https://doi.org/10.1093/chromsci/bmx018 . .

TY  - JOUR
AU  - Protić, Ana
AU  - Radisić, Marina
AU  - Golubović, Jelena
AU  - Otašević, Biljana
AU  - Zečević, Mira
AU  - Lausević, Mila
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2746
AB  - Unknown degradation products of mycophenolate mofetil formed under oxidative stress conditions have been characterized via LC-MSn, using an RP-LC column (50 mm length, 2.1 mm i.d., 1.9 A mu m). The mobile phase consisted of 26 % acetonitrile and 74 % 9 mM ammonium acetate pH 5.87, the column temperature was set at 40 A degrees C, and the flow rate of the mobile phase was 400 A mu L min(-1). Four degradation products formed under the influence of 15 % hydrogen peroxide after an hour. Two of the degradation products had previously been identified as mycophenolic acid (m/z 321) and the N-oxide of mycophenolate mofetil (m/z 450). The other two unknown degradation products, denoted DP I (m/z 319) and DP II (m/z 466), were investigated in depth in order to identify their structures. The fragmentation patterns of DP I and DP II were established, analyzed, and compared to the fragmentation patterns of mycophenolate mofetil and the N-oxide of mycophenolate mofetil, which aided the elucidation of the structures of the unknown degradation products. The unknown degradation product DP I (m/z 319.2) was proposed to be an oxidized unsaturated mycophenolate aldehyde which also appeared as an ammonium adduct ion at m/z 336.3. The second unknown degradation product, DP II (m/z 466.3), was characterized as a doubly oxidized derivative of mycophenolate mofetil. A possible degradation pathway of mycophenolate mofetil under the influence of an oxidizing agent was also proposed.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn
VL  - 79
IS  - 13-14
SP  - 919
EP  - 926
DO  - 10.1007/s10337-016-3092-2
ER  - 

@article{
author = "Protić, Ana and Radisić, Marina and Golubović, Jelena and Otašević, Biljana and Zečević, Mira and Lausević, Mila",
year = "2016",
abstract = "Unknown degradation products of mycophenolate mofetil formed under oxidative stress conditions have been characterized via LC-MSn, using an RP-LC column (50 mm length, 2.1 mm i.d., 1.9 A mu m). The mobile phase consisted of 26 % acetonitrile and 74 % 9 mM ammonium acetate pH 5.87, the column temperature was set at 40 A degrees C, and the flow rate of the mobile phase was 400 A mu L min(-1). Four degradation products formed under the influence of 15 % hydrogen peroxide after an hour. Two of the degradation products had previously been identified as mycophenolic acid (m/z 321) and the N-oxide of mycophenolate mofetil (m/z 450). The other two unknown degradation products, denoted DP I (m/z 319) and DP II (m/z 466), were investigated in depth in order to identify their structures. The fragmentation patterns of DP I and DP II were established, analyzed, and compared to the fragmentation patterns of mycophenolate mofetil and the N-oxide of mycophenolate mofetil, which aided the elucidation of the structures of the unknown degradation products. The unknown degradation product DP I (m/z 319.2) was proposed to be an oxidized unsaturated mycophenolate aldehyde which also appeared as an ammonium adduct ion at m/z 336.3. The second unknown degradation product, DP II (m/z 466.3), was characterized as a doubly oxidized derivative of mycophenolate mofetil. A possible degradation pathway of mycophenolate mofetil under the influence of an oxidizing agent was also proposed.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn",
volume = "79",
number = "13-14",
pages = "919-926",
doi = "10.1007/s10337-016-3092-2"
}

Protić, A., Radisić, M., Golubović, J., Otašević, B., Zečević, M.,& Lausević, M.. (2016). Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn. in Chromatographia
Springer Heidelberg, Heidelberg., 79(13-14), 919-926.
https://doi.org/10.1007/s10337-016-3092-2

Protić A, Radisić M, Golubović J, Otašević B, Zečević M, Lausević M. Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn. in Chromatographia. 2016;79(13-14):919-926.
doi:10.1007/s10337-016-3092-2 .

Protić, Ana, Radisić, Marina, Golubović, Jelena, Otašević, Biljana, Zečević, Mira, Lausević, Mila, "Structural Elucidation of Unknown Oxidative Degradation Products of Mycophenolate Mofetil Using LC-MSn" in Chromatographia, 79, no. 13-14 (2016):919-926,
https://doi.org/10.1007/s10337-016-3092-2 . .

TY  - JOUR
AU  - Golubović, Jelena
AU  - Protić, Ana
AU  - Otašević, Biljana
AU  - Zečević, Mira
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2563
AB  - QSRR are mathematically derived relationships between the chromatographic parameters determined for a representative series of analytes in given separation systems and the molecular descriptors accounting for the structural differences among the investigated "analytes. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. The aim of the present work was to optimize separation of six angiotensin receptor antagonists, so-called sartans: losartan, valsartan, irbesartan, telmisartan, candesartan cilexetil and eprosartan in a gradient-elution HPLC method. For this purpose, ANN as a mathematical tool was used for establishing a QSRR model based on molecular descriptors of sartans and varied instrumental conditions. The optimized model can be further used for prediction of an external congener of sartans and analysis of the influence of the analyte structure, represented through molecular descriptors, on retention behaviour. Molecular descriptors included in modelling were electrostatic, geometrical and quantum-chemical descriptors: connolly solvent excluded volume non-1,4 van der Waals energy, octanol/water distribution coefficient, polarizability, number of proton-donor sites and number of proton-acceptor sites. Varied instrumental conditions were gradient time, buffer pH and buffer molarity. High prediction ability of the optimized network enabled complete separation of the analytes within the run time of 15.5 min under following conditions: gradient time of 12.5 min, buffer pH of 3.95 and buffer molarity of 25 mM. Applied methodology showed the potential to predict retention behaviour of an external analyte with the properties within the training space. Connolly solvent excluded volume, polarizability and number of proton-acceptor sites appeared to be most influential paramateres on retention behaviour of the sartans.
PB  - Elsevier Science BV, Amsterdam
T2  - Talanta
T1  - Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans
VL  - 150
SP  - 190
EP  - 197
DO  - 10.1016/j.talanta.2015.12.035
ER  - 

@article{
author = "Golubović, Jelena and Protić, Ana and Otašević, Biljana and Zečević, Mira",
year = "2016",
abstract = "QSRR are mathematically derived relationships between the chromatographic parameters determined for a representative series of analytes in given separation systems and the molecular descriptors accounting for the structural differences among the investigated "analytes. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. The aim of the present work was to optimize separation of six angiotensin receptor antagonists, so-called sartans: losartan, valsartan, irbesartan, telmisartan, candesartan cilexetil and eprosartan in a gradient-elution HPLC method. For this purpose, ANN as a mathematical tool was used for establishing a QSRR model based on molecular descriptors of sartans and varied instrumental conditions. The optimized model can be further used for prediction of an external congener of sartans and analysis of the influence of the analyte structure, represented through molecular descriptors, on retention behaviour. Molecular descriptors included in modelling were electrostatic, geometrical and quantum-chemical descriptors: connolly solvent excluded volume non-1,4 van der Waals energy, octanol/water distribution coefficient, polarizability, number of proton-donor sites and number of proton-acceptor sites. Varied instrumental conditions were gradient time, buffer pH and buffer molarity. High prediction ability of the optimized network enabled complete separation of the analytes within the run time of 15.5 min under following conditions: gradient time of 12.5 min, buffer pH of 3.95 and buffer molarity of 25 mM. Applied methodology showed the potential to predict retention behaviour of an external analyte with the properties within the training space. Connolly solvent excluded volume, polarizability and number of proton-acceptor sites appeared to be most influential paramateres on retention behaviour of the sartans.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Talanta",
title = "Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans",
volume = "150",
pages = "190-197",
doi = "10.1016/j.talanta.2015.12.035"
}

Golubović, J., Protić, A., Otašević, B.,& Zečević, M.. (2016). Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans. in Talanta
Elsevier Science BV, Amsterdam., 150, 190-197.
https://doi.org/10.1016/j.talanta.2015.12.035

Golubović J, Protić A, Otašević B, Zečević M. Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans. in Talanta. 2016;150:190-197.
doi:10.1016/j.talanta.2015.12.035 .

Golubović, Jelena, Protić, Ana, Otašević, Biljana, Zečević, Mira, "Quantitative structure-retention relationships applied to development of liquid chromatography gradient-elution method for the separation of sartans" in Talanta, 150 (2016):190-197,
https://doi.org/10.1016/j.talanta.2015.12.035 . .

TY  - JOUR
AU  - Golubović, Jelena
AU  - Birkemeyer, Claudia
AU  - Protić, Ana
AU  - Otašević, Biljana
AU  - Zečević, Mira
PY  - 2016
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2541
AB  - Quantitative structure-property relationship (QSPR) methods are based on the hypothesis that changes in the molecular structure are reflected in changes in the observed property of the molecule. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. For the first time a quantitative structure-response relationship in electrospray ionization mass spectrometry (ESI-MS) by means of artificial neural networks (ANN) on the group of angiotensin II receptor antagonists - sartans has been established. The investigated descriptors correspond to different properties of the analytes: polarity (logP), ionizability (pKa), surface area (solvent excluded volume) and number of proton acceptors. The influence of the instrumental parameters: methanol content in mobile phase, mobile phase pH and flow rate was also examined. Best performance showed a multilayer perceptron network with the architecture 6-3-3-1, trained with backpropagation algorithm. It showed high prediction ability on the previously unseen (test) data set with a coefficient of determination of 0.994. High prediction ability of the model would enable prediction of ESI-MS responsiveness under different conditions. This is particularly important in the method development phase. Also, prediction of responsiveness can be important in case of gradient-elution LC-MS and LC-MS/MS methods in which instrumental conditions are varied during time. Polarity, chargeability and surface area all appeared to be crucial for electrospray ionization whereby signal intensity appeared to be the result of a simultaneous influence of the molecular descriptors and their interactions. Percentage of organic phase in the mobile phase showed a positive, while flow rate showed a negative impact on signal intensity.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Chromatography A
T1  - Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks
VL  - 1438
SP  - 123
EP  - 132
DO  - 10.1016/j.chroma.2016.02.021
ER  - 

@article{
author = "Golubović, Jelena and Birkemeyer, Claudia and Protić, Ana and Otašević, Biljana and Zečević, Mira",
year = "2016",
abstract = "Quantitative structure-property relationship (QSPR) methods are based on the hypothesis that changes in the molecular structure are reflected in changes in the observed property of the molecule. Artificial neural network is a technique of data analysis, which sets out to emulate the human brain's way of working. For the first time a quantitative structure-response relationship in electrospray ionization mass spectrometry (ESI-MS) by means of artificial neural networks (ANN) on the group of angiotensin II receptor antagonists - sartans has been established. The investigated descriptors correspond to different properties of the analytes: polarity (logP), ionizability (pKa), surface area (solvent excluded volume) and number of proton acceptors. The influence of the instrumental parameters: methanol content in mobile phase, mobile phase pH and flow rate was also examined. Best performance showed a multilayer perceptron network with the architecture 6-3-3-1, trained with backpropagation algorithm. It showed high prediction ability on the previously unseen (test) data set with a coefficient of determination of 0.994. High prediction ability of the model would enable prediction of ESI-MS responsiveness under different conditions. This is particularly important in the method development phase. Also, prediction of responsiveness can be important in case of gradient-elution LC-MS and LC-MS/MS methods in which instrumental conditions are varied during time. Polarity, chargeability and surface area all appeared to be crucial for electrospray ionization whereby signal intensity appeared to be the result of a simultaneous influence of the molecular descriptors and their interactions. Percentage of organic phase in the mobile phase showed a positive, while flow rate showed a negative impact on signal intensity.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Chromatography A",
title = "Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks",
volume = "1438",
pages = "123-132",
doi = "10.1016/j.chroma.2016.02.021"
}

Golubović, J., Birkemeyer, C., Protić, A., Otašević, B.,& Zečević, M.. (2016). Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks. in Journal of Chromatography A
Elsevier Science BV, Amsterdam., 1438, 123-132.
https://doi.org/10.1016/j.chroma.2016.02.021

Golubović J, Birkemeyer C, Protić A, Otašević B, Zečević M. Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks. in Journal of Chromatography A. 2016;1438:123-132.
doi:10.1016/j.chroma.2016.02.021 .

Golubović, Jelena, Birkemeyer, Claudia, Protić, Ana, Otašević, Biljana, Zečević, Mira, "Structure-response relationship in electrospray ionization-mass spectrometry of sartans by artificial neural networks" in Journal of Chromatography A, 1438 (2016):123-132,
https://doi.org/10.1016/j.chroma.2016.02.021 . .

TY  - JOUR
AU  - Otašević, Biljana
AU  - Protić, Ana
AU  - Golubović, Jelena
AU  - Zečević, Mira
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2497
AB  - Liquid chromatography is the most widely used analytical technique in course of research and development, as well as for routine investigation and quality control of pharmaceutical products. Having in mind the remarkable amount of waist resulting from the use of organic solvents, especially for reversed-phase liquid chromatography, recently ecologically acceptable concepts in chromatographic method development were noticed. The 3 Rrule (Reduce - Replace - Recycle) refers to the decrease of the toxic solvents use, their replacement with less toxic ones and the use of renewable solvents. This paper presents different solutions commonly applied in drug analysis that are in accordance with the 3 Rrule.
AB  - Tečna hromatografija predstavlja najčešće korišćenu analitičku tehniku tokom istraživanja i razvoja, kao i u rutinskom ispitivanju i kontroli kvaliteta farmaceutskih proizvoda. Imajući u vidu značajnu količinu otpada koji potiče od upotrebljenih organskih rastvarača, naročito kod reverzno-fazne tečne hromatografije, zabeleženi su novi koncepti razvoja ekološki prihvatljive hromatografske metode. Pravilo 3 R (eng. Reduce - Replace - Recycle) podrazumeva smanjenu upotrebu toksičnih rastvarača, njihovu zamenu manje toksičnim rastvaračima, kao i rastvaračima koji se mogu prerađivati. U ovom radu su predstavljena različita rešenja koja zadovoljavaju 3 R pravila i često se primenjuju u analitici lekova.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - The application of ecologically acceptable concept in liquid chromatographic method development in drug analyses
T1  - Primena koncepta razvoja ekološki prihvatljivih metoda tečne hromatografije u analitici lekova
VL  - 65
IS  - 3
SP  - 178
EP  - 190
DO  - 10.5937/arhfarm1503178O
ER  - 

@article{
author = "Otašević, Biljana and Protić, Ana and Golubović, Jelena and Zečević, Mira",
year = "2015",
abstract = "Liquid chromatography is the most widely used analytical technique in course of research and development, as well as for routine investigation and quality control of pharmaceutical products. Having in mind the remarkable amount of waist resulting from the use of organic solvents, especially for reversed-phase liquid chromatography, recently ecologically acceptable concepts in chromatographic method development were noticed. The 3 Rrule (Reduce - Replace - Recycle) refers to the decrease of the toxic solvents use, their replacement with less toxic ones and the use of renewable solvents. This paper presents different solutions commonly applied in drug analysis that are in accordance with the 3 Rrule., Tečna hromatografija predstavlja najčešće korišćenu analitičku tehniku tokom istraživanja i razvoja, kao i u rutinskom ispitivanju i kontroli kvaliteta farmaceutskih proizvoda. Imajući u vidu značajnu količinu otpada koji potiče od upotrebljenih organskih rastvarača, naročito kod reverzno-fazne tečne hromatografije, zabeleženi su novi koncepti razvoja ekološki prihvatljive hromatografske metode. Pravilo 3 R (eng. Reduce - Replace - Recycle) podrazumeva smanjenu upotrebu toksičnih rastvarača, njihovu zamenu manje toksičnim rastvaračima, kao i rastvaračima koji se mogu prerađivati. U ovom radu su predstavljena različita rešenja koja zadovoljavaju 3 R pravila i često se primenjuju u analitici lekova.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "The application of ecologically acceptable concept in liquid chromatographic method development in drug analyses, Primena koncepta razvoja ekološki prihvatljivih metoda tečne hromatografije u analitici lekova",
volume = "65",
number = "3",
pages = "178-190",
doi = "10.5937/arhfarm1503178O"
}

Otašević, B., Protić, A., Golubović, J.,& Zečević, M.. (2015). The application of ecologically acceptable concept in liquid chromatographic method development in drug analyses. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 65(3), 178-190.
https://doi.org/10.5937/arhfarm1503178O

Otašević B, Protić A, Golubović J, Zečević M. The application of ecologically acceptable concept in liquid chromatographic method development in drug analyses. in Arhiv za farmaciju. 2015;65(3):178-190.
doi:10.5937/arhfarm1503178O .

Otašević, Biljana, Protić, Ana, Golubović, Jelena, Zečević, Mira, "The application of ecologically acceptable concept in liquid chromatographic method development in drug analyses" in Arhiv za farmaciju, 65, no. 3 (2015):178-190,
https://doi.org/10.5937/arhfarm1503178O . .

TY  - JOUR
AU  - Golubović, Jelena
AU  - Protić, Ana
AU  - Zečević, Mira
AU  - Otašević, Biljana
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2403
AB  - Artificial neural network (ANN) is a learning system based on a computation technique, which was employed for building of the quantitative structure-retention relationship (QSRR) model for candesartan cilexetil and its degradation products. Candesartan cilexetil has been exposed to forced degradation conditions and degradation products have been subsequently identified with the assistance of HPLC-MS technique. Molecular descriptors have been computed for all compounds and were optimized together with significant chromatographic parameters employing developed QSRR models. In this way, QSRR has been used in development of HPLC stabilityindicating method, optimal conditions toward various outputs have been established and high prediction potential of the created QSRR models has been proved.
PB  - Elsevier Science BV, Amsterdam
T2  - Chemometrics and Intelligent Laboratory Systems
T1  - Quantitative structure retention relationship modeling in liquid chromatography method for separation of candesartan cilexetil and its degradation products
VL  - 140
SP  - 92
EP  - 101
DO  - 10.1016/j.chemolab.2014.11.005
ER  - 

@article{
author = "Golubović, Jelena and Protić, Ana and Zečević, Mira and Otašević, Biljana",
year = "2015",
abstract = "Artificial neural network (ANN) is a learning system based on a computation technique, which was employed for building of the quantitative structure-retention relationship (QSRR) model for candesartan cilexetil and its degradation products. Candesartan cilexetil has been exposed to forced degradation conditions and degradation products have been subsequently identified with the assistance of HPLC-MS technique. Molecular descriptors have been computed for all compounds and were optimized together with significant chromatographic parameters employing developed QSRR models. In this way, QSRR has been used in development of HPLC stabilityindicating method, optimal conditions toward various outputs have been established and high prediction potential of the created QSRR models has been proved.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Chemometrics and Intelligent Laboratory Systems",
title = "Quantitative structure retention relationship modeling in liquid chromatography method for separation of candesartan cilexetil and its degradation products",
volume = "140",
pages = "92-101",
doi = "10.1016/j.chemolab.2014.11.005"
}

Golubović, J., Protić, A., Zečević, M.,& Otašević, B.. (2015). Quantitative structure retention relationship modeling in liquid chromatography method for separation of candesartan cilexetil and its degradation products. in Chemometrics and Intelligent Laboratory Systems
Elsevier Science BV, Amsterdam., 140, 92-101.
https://doi.org/10.1016/j.chemolab.2014.11.005

Golubović J, Protić A, Zečević M, Otašević B. Quantitative structure retention relationship modeling in liquid chromatography method for separation of candesartan cilexetil and its degradation products. in Chemometrics and Intelligent Laboratory Systems. 2015;140:92-101.
doi:10.1016/j.chemolab.2014.11.005 .

Golubović, Jelena, Protić, Ana, Zečević, Mira, Otašević, Biljana, "Quantitative structure retention relationship modeling in liquid chromatography method for separation of candesartan cilexetil and its degradation products" in Chemometrics and Intelligent Laboratory Systems, 140 (2015):92-101,
https://doi.org/10.1016/j.chemolab.2014.11.005 . .

TY  - JOUR
AU  - Golubović, Jelena
AU  - Otašević, Biljana
AU  - Protić, Ana
AU  - Stanković, Aleksandra M.
AU  - Zečević, Mira
PY  - 2015
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2303
AB  - RationaleUndeclared corticosteroids in creams intended for frequent use might cause serious side-effects, especially in children. In order to prevent this or find the cause, it was essential to develop a method for quick detection and quantification of low levels of corticosteroids. MethodsEleven corticosteroids were used in this study: prednisolone, methylprednisolone, prednisolone-21-acetate, fluocinolone acetonide, fluocinolone acetonide-21-acetate, hydrocortisone-21-acetate, dexamethasone, betamethasone, betamethasone dipropionate, clobetasol propionate and triamcinolone. Separation was achieved via liquid chromatography (LC), and mass spectrometric analysis was conducted by electrospray ionization triple-quadrupole mass spectrometry (MS/MS) in the multiple reaction monitoring mode using corticosterone as internal standard. ResultsGood separation by using a gradient-elution LC/MS/MS method with run time of 25min enabled the use of a segmented detection method and consecutive decrease in detection limits. The proposed method has been validated in the linearity range of 10-1000ng/mL with coefficients of determination higher than 0.990. The method has shown to have very low limits of quantification (0.75-3ng/mL) with satisfactory precision and accuracy for each of the corticosteroids. ConclusionsAn LC/MS/MS method for the rapid and simultaneous determination of low levels of eleven topical corticosteroids in creams was developed, optimized and validated. The proposed method can be used for testing of different products indicated for the treatment of atopic dermatitis, including "natural products", and "herbal creams" with "miraculous effects". Copyright
PB  - Wiley, Hoboken
T2  - Rapid Communications in Mass Spectrometry
T1  - Liquid chromatography/tandem mass spectrometry for simultaneous determination of undeclared corticosteroids in cosmetic creams
VL  - 29
IS  - 24
SP  - 2319
EP  - 2327
DO  - 10.1002/rcm.7403
ER  - 

@article{
author = "Golubović, Jelena and Otašević, Biljana and Protić, Ana and Stanković, Aleksandra M. and Zečević, Mira",
year = "2015",
abstract = "RationaleUndeclared corticosteroids in creams intended for frequent use might cause serious side-effects, especially in children. In order to prevent this or find the cause, it was essential to develop a method for quick detection and quantification of low levels of corticosteroids. MethodsEleven corticosteroids were used in this study: prednisolone, methylprednisolone, prednisolone-21-acetate, fluocinolone acetonide, fluocinolone acetonide-21-acetate, hydrocortisone-21-acetate, dexamethasone, betamethasone, betamethasone dipropionate, clobetasol propionate and triamcinolone. Separation was achieved via liquid chromatography (LC), and mass spectrometric analysis was conducted by electrospray ionization triple-quadrupole mass spectrometry (MS/MS) in the multiple reaction monitoring mode using corticosterone as internal standard. ResultsGood separation by using a gradient-elution LC/MS/MS method with run time of 25min enabled the use of a segmented detection method and consecutive decrease in detection limits. The proposed method has been validated in the linearity range of 10-1000ng/mL with coefficients of determination higher than 0.990. The method has shown to have very low limits of quantification (0.75-3ng/mL) with satisfactory precision and accuracy for each of the corticosteroids. ConclusionsAn LC/MS/MS method for the rapid and simultaneous determination of low levels of eleven topical corticosteroids in creams was developed, optimized and validated. The proposed method can be used for testing of different products indicated for the treatment of atopic dermatitis, including "natural products", and "herbal creams" with "miraculous effects". Copyright",
publisher = "Wiley, Hoboken",
journal = "Rapid Communications in Mass Spectrometry",
title = "Liquid chromatography/tandem mass spectrometry for simultaneous determination of undeclared corticosteroids in cosmetic creams",
volume = "29",
number = "24",
pages = "2319-2327",
doi = "10.1002/rcm.7403"
}

Golubović, J., Otašević, B., Protić, A., Stanković, A. M.,& Zečević, M.. (2015). Liquid chromatography/tandem mass spectrometry for simultaneous determination of undeclared corticosteroids in cosmetic creams. in Rapid Communications in Mass Spectrometry
Wiley, Hoboken., 29(24), 2319-2327.
https://doi.org/10.1002/rcm.7403

Golubović J, Otašević B, Protić A, Stanković AM, Zečević M. Liquid chromatography/tandem mass spectrometry for simultaneous determination of undeclared corticosteroids in cosmetic creams. in Rapid Communications in Mass Spectrometry. 2015;29(24):2319-2327.
doi:10.1002/rcm.7403 .

Golubović, Jelena, Otašević, Biljana, Protić, Ana, Stanković, Aleksandra M., Zečević, Mira, "Liquid chromatography/tandem mass spectrometry for simultaneous determination of undeclared corticosteroids in cosmetic creams" in Rapid Communications in Mass Spectrometry, 29, no. 24 (2015):2319-2327,
https://doi.org/10.1002/rcm.7403 . .

TY  - JOUR
AU  - Otašević, Biljana
AU  - Protić, Ana
AU  - Golubović, Jelena
AU  - Zečević, Mira
AU  - Cerović, Milica
AU  - Bralović, Ljubica
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2281
AB  - Pharmacological effect of a drug depends on its free fraction in plasma. By certain drugs, like immunosupresive mycophenolic acid, concentrations below therapeutic lead to rejection of the transplanted organ while concentrations above therapeutic lead to toxic effects, primarily on kidney and liver. For this reason constant monitoring of mycophenolic acid in plasma is necessary. Concerning frequency of sampling, availability and non-invasive way of sampling, saliva presents one of the best biological materials for analysis. On the other hand, numerous interfering endogen substances, impurities and high viscosity of saliva make this biological material difficult for purification. Mycophenolic acid has to be purified and concentrated from saliva to be consequently determined applying appropriate analytical method. In this paper solid phase extraction method for purification of saliva has been presented. The efficacy of solid phase extraction has been influenced by many different experimental parameters, so these parameters has to be strongly controlled, and protocol of extraction procedure has been proposed. In this way conditioning of polymeric sorbent has been done with methanol and purified water, samples have been applied together with 0.1 % formic acid, washing has been done with purified water and elution of mycophenolic acid has been performed with acetonitrile and 0.2% formic acid.
AB  - Farmakološki efekti leka direktno zavise od koncentracije leka u plazmi, odnosno njegove slobodne frakcije. Kod određenih lekova, kao što je imunosupresiv mikofenolna kiselina, smanjenje koncentracije dovodi do izostanka terapijskog efekta, dok povećanje koncentracije može dovesti do toksičnih efekata. Ozbiljni neželjeni efekti mogu dovesti do fatalnih ishoda, bilo da se radi o odbacivanju transplantiranog organa ili ozbiljnom oštećenju bubrega i jetre. Iz tog razloga potrebno je sprovoditi stalno praćenje nivoa mikofenolne kiseline u krvi. Imajući u vidu učestalost uzorkovanja, dostupnost i neinvazivan način sakupljanja, saliva ima prednost nad plazmom zbog čega se u skorije vreme sve više koristi kao uzorak. Međutim, zbog brojnih interferirajućih endogenih supstanci, nečistoća i viskoznosti, salivu je neophodno prethodno obraditi za kvalitativno i kvantitativno praćenje mikofenolne kiseline UPLC metodom. U ovom radu je opisana upotreba čvrsto-tečne ekstrakcije kao metode izbora za pripremu uzoraka salive. Pošto na efikasnost ekstrakcije utiču različiti eksperimentalni uslovi koje je potrebno strogo kontrolisati, predložen je protokol koji podrazumeva: kondicioniranje polimernog kertridža za čvrsto-tečnu ekstrakciju metanolom i vodom, nanošenje uzorka zajedno sa 0,1 % mravljom kiselinom, ispiranje kertridža vodom i eluiranje mikofenolne kiseline smešom acetonitrila i 0,2% mravlje kiseline.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Analysis of mycophenolic acid from saliva samples after its purification with the method of solidliquid extraction
T1  - Razvoj metode čvrsto-tečne ekstrakcije za prečišćavanje mikofenolne kiseline iz uzoraka salive
VL  - 64
IS  - 3
SP  - 247
EP  - 260
DO  - 10.5937/arhfarm1403247O
ER  - 

@article{
author = "Otašević, Biljana and Protić, Ana and Golubović, Jelena and Zečević, Mira and Cerović, Milica and Bralović, Ljubica",
year = "2014",
abstract = "Pharmacological effect of a drug depends on its free fraction in plasma. By certain drugs, like immunosupresive mycophenolic acid, concentrations below therapeutic lead to rejection of the transplanted organ while concentrations above therapeutic lead to toxic effects, primarily on kidney and liver. For this reason constant monitoring of mycophenolic acid in plasma is necessary. Concerning frequency of sampling, availability and non-invasive way of sampling, saliva presents one of the best biological materials for analysis. On the other hand, numerous interfering endogen substances, impurities and high viscosity of saliva make this biological material difficult for purification. Mycophenolic acid has to be purified and concentrated from saliva to be consequently determined applying appropriate analytical method. In this paper solid phase extraction method for purification of saliva has been presented. The efficacy of solid phase extraction has been influenced by many different experimental parameters, so these parameters has to be strongly controlled, and protocol of extraction procedure has been proposed. In this way conditioning of polymeric sorbent has been done with methanol and purified water, samples have been applied together with 0.1 % formic acid, washing has been done with purified water and elution of mycophenolic acid has been performed with acetonitrile and 0.2% formic acid., Farmakološki efekti leka direktno zavise od koncentracije leka u plazmi, odnosno njegove slobodne frakcije. Kod određenih lekova, kao što je imunosupresiv mikofenolna kiselina, smanjenje koncentracije dovodi do izostanka terapijskog efekta, dok povećanje koncentracije može dovesti do toksičnih efekata. Ozbiljni neželjeni efekti mogu dovesti do fatalnih ishoda, bilo da se radi o odbacivanju transplantiranog organa ili ozbiljnom oštećenju bubrega i jetre. Iz tog razloga potrebno je sprovoditi stalno praćenje nivoa mikofenolne kiseline u krvi. Imajući u vidu učestalost uzorkovanja, dostupnost i neinvazivan način sakupljanja, saliva ima prednost nad plazmom zbog čega se u skorije vreme sve više koristi kao uzorak. Međutim, zbog brojnih interferirajućih endogenih supstanci, nečistoća i viskoznosti, salivu je neophodno prethodno obraditi za kvalitativno i kvantitativno praćenje mikofenolne kiseline UPLC metodom. U ovom radu je opisana upotreba čvrsto-tečne ekstrakcije kao metode izbora za pripremu uzoraka salive. Pošto na efikasnost ekstrakcije utiču različiti eksperimentalni uslovi koje je potrebno strogo kontrolisati, predložen je protokol koji podrazumeva: kondicioniranje polimernog kertridža za čvrsto-tečnu ekstrakciju metanolom i vodom, nanošenje uzorka zajedno sa 0,1 % mravljom kiselinom, ispiranje kertridža vodom i eluiranje mikofenolne kiseline smešom acetonitrila i 0,2% mravlje kiseline.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Analysis of mycophenolic acid from saliva samples after its purification with the method of solidliquid extraction, Razvoj metode čvrsto-tečne ekstrakcije za prečišćavanje mikofenolne kiseline iz uzoraka salive",
volume = "64",
number = "3",
pages = "247-260",
doi = "10.5937/arhfarm1403247O"
}

Otašević, B., Protić, A., Golubović, J., Zečević, M., Cerović, M.,& Bralović, L.. (2014). Analysis of mycophenolic acid from saliva samples after its purification with the method of solidliquid extraction. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 64(3), 247-260.
https://doi.org/10.5937/arhfarm1403247O

Otašević B, Protić A, Golubović J, Zečević M, Cerović M, Bralović L. Analysis of mycophenolic acid from saliva samples after its purification with the method of solidliquid extraction. in Arhiv za farmaciju. 2014;64(3):247-260.
doi:10.5937/arhfarm1403247O .

Otašević, Biljana, Protić, Ana, Golubović, Jelena, Zečević, Mira, Cerović, Milica, Bralović, Ljubica, "Analysis of mycophenolic acid from saliva samples after its purification with the method of solidliquid extraction" in Arhiv za farmaciju, 64, no. 3 (2014):247-260,
https://doi.org/10.5937/arhfarm1403247O . .

TY  - JOUR
AU  - Otašević, Biljana
AU  - Milovanović, Svetlana
AU  - Zečević, Mira
AU  - Golubović, Jelena
AU  - Protić, Ana
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2186
AB  - A simple, rapid, isocratic, stability-indicating reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed and validated for the routine analysis of moxonidine in the presence of its degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms. Forced degradation studies were performed according to the guidance of International Conference for Harmonization and were used to evaluate moxonidine intrinsic stability. The drug was subjected to acid, neutral and base hydrolysis as well as to oxidative, thermal and photolytic decomposition in both solution and solid state. The drug appeared to be unstable towards acid and base hydrolysis. To achieve desirable conditions for UPLC analysis, the method development was done with the assistance of experimental design and multivariate optimization methodology by means of Derringer's desirability function. Stress samples were analyzed according to the experimental plan for fractional factorial screening design and Box-Behnken optimization design. The chromatographic separation was achieved on a C-18 Hypersil Gold aq. column (100 mm x 2.1 mm, 1.9 mu m) with the mobile phase consisting of methanol-ammonium acetate buffer (10 mM, pH 3.43) mixture (0.9:99.1, v/v) pumped at a flow rate of 870 mu L min(-1) and detection wavelength of 255 nm. The UPLC-MS and UPLC-MS/MS analyses were further used to characterize the found degradation products. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial tablets.
PB  - Springer Heidelberg, Heidelberg
T2  - Chromatographia
T1  - UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form
VL  - 77
IS  - 1-2
SP  - 109
EP  - 118
DO  - 10.1007/s10337-013-2580-x
ER  - 

@article{
author = "Otašević, Biljana and Milovanović, Svetlana and Zečević, Mira and Golubović, Jelena and Protić, Ana",
year = "2014",
abstract = "A simple, rapid, isocratic, stability-indicating reverse phase ultra-performance liquid chromatographic (RP-UPLC) method was developed and validated for the routine analysis of moxonidine in the presence of its degradation products in active pharmaceutical ingredient and pharmaceutical dosage forms. Forced degradation studies were performed according to the guidance of International Conference for Harmonization and were used to evaluate moxonidine intrinsic stability. The drug was subjected to acid, neutral and base hydrolysis as well as to oxidative, thermal and photolytic decomposition in both solution and solid state. The drug appeared to be unstable towards acid and base hydrolysis. To achieve desirable conditions for UPLC analysis, the method development was done with the assistance of experimental design and multivariate optimization methodology by means of Derringer's desirability function. Stress samples were analyzed according to the experimental plan for fractional factorial screening design and Box-Behnken optimization design. The chromatographic separation was achieved on a C-18 Hypersil Gold aq. column (100 mm x 2.1 mm, 1.9 mu m) with the mobile phase consisting of methanol-ammonium acetate buffer (10 mM, pH 3.43) mixture (0.9:99.1, v/v) pumped at a flow rate of 870 mu L min(-1) and detection wavelength of 255 nm. The UPLC-MS and UPLC-MS/MS analyses were further used to characterize the found degradation products. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial tablets.",
publisher = "Springer Heidelberg, Heidelberg",
journal = "Chromatographia",
title = "UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form",
volume = "77",
number = "1-2",
pages = "109-118",
doi = "10.1007/s10337-013-2580-x"
}

Otašević, B., Milovanović, S., Zečević, M., Golubović, J.,& Protić, A.. (2014). UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form. in Chromatographia
Springer Heidelberg, Heidelberg., 77(1-2), 109-118.
https://doi.org/10.1007/s10337-013-2580-x

Otašević B, Milovanović S, Zečević M, Golubović J, Protić A. UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form. in Chromatographia. 2014;77(1-2):109-118.
doi:10.1007/s10337-013-2580-x .

Otašević, Biljana, Milovanović, Svetlana, Zečević, Mira, Golubović, Jelena, Protić, Ana, "UPLC Method for Determination of Moxonidine and Its Degradation Products in Active Pharmaceutical Ingredient and Pharmaceutical Dosage Form" in Chromatographia, 77, no. 1-2 (2014):109-118,
https://doi.org/10.1007/s10337-013-2580-x . .

TY  - JOUR
AU  - Golubović, Jelena
AU  - Protić, Ana
AU  - Zečević, Mira
AU  - Otašević, Biljana
AU  - Mikić, Marija
PY  - 2014
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2094
AB  - The study of experimental design in conjunction with artificial neural networks for optimization of isocratic ultra performance liquid chromatography method for separation of mycophenolate mofetil and its degradation products has been reported. Experimental design showed to be suitable for selection of experimental scheme, while Kennard-Stone algorithm was used for selection of training data set. The input variables were column temperature and composition of mobile phase including percentage of acetonitrile, concentration of ammonium acetate in buffer, and its pH value. The retention factor of the most retentive component and selectivity factors were used as the dependent variables (outputs). In this way, artificial neural network has been applied as a predictable tool in solving a method optimization problem using small number of experiments. Network architecture and training parameters were optimized to the lowest root-mean-square error values, and the network with 5-4-4-4 topology has been selected as the most predictable one. Predicted data were in good agreement with experimental data, and regression statistics confirmed good ability of trained network to predict compounds retention. The optimal chromatographic conditions included column temperature of 40 degrees C, flow rate of 700 mu l min(-1), 26% of acetonitrile and 9 mM ammonium acetate in mobile phase, and buffer pH of 5.87. The chromatographic analysis has been achieved within 5.2 min. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection, and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial dosage form. Copyright
PB  - Wiley-Blackwell, Hoboken
T2  - Journal of Chemometrics
T1  - Artificial neural networks modeling in ultra performance liquid chromatography method optimization of mycophenolate mofetil and its degradation products
VL  - 28
IS  - 7
SP  - 567
EP  - 574
DO  - 10.1002/cem.2616
ER  - 

@article{
author = "Golubović, Jelena and Protić, Ana and Zečević, Mira and Otašević, Biljana and Mikić, Marija",
year = "2014",
abstract = "The study of experimental design in conjunction with artificial neural networks for optimization of isocratic ultra performance liquid chromatography method for separation of mycophenolate mofetil and its degradation products has been reported. Experimental design showed to be suitable for selection of experimental scheme, while Kennard-Stone algorithm was used for selection of training data set. The input variables were column temperature and composition of mobile phase including percentage of acetonitrile, concentration of ammonium acetate in buffer, and its pH value. The retention factor of the most retentive component and selectivity factors were used as the dependent variables (outputs). In this way, artificial neural network has been applied as a predictable tool in solving a method optimization problem using small number of experiments. Network architecture and training parameters were optimized to the lowest root-mean-square error values, and the network with 5-4-4-4 topology has been selected as the most predictable one. Predicted data were in good agreement with experimental data, and regression statistics confirmed good ability of trained network to predict compounds retention. The optimal chromatographic conditions included column temperature of 40 degrees C, flow rate of 700 mu l min(-1), 26% of acetonitrile and 9 mM ammonium acetate in mobile phase, and buffer pH of 5.87. The chromatographic analysis has been achieved within 5.2 min. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection, and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial dosage form. Copyright",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Journal of Chemometrics",
title = "Artificial neural networks modeling in ultra performance liquid chromatography method optimization of mycophenolate mofetil and its degradation products",
volume = "28",
number = "7",
pages = "567-574",
doi = "10.1002/cem.2616"
}

Golubović, J., Protić, A., Zečević, M., Otašević, B.,& Mikić, M.. (2014). Artificial neural networks modeling in ultra performance liquid chromatography method optimization of mycophenolate mofetil and its degradation products. in Journal of Chemometrics
Wiley-Blackwell, Hoboken., 28(7), 567-574.
https://doi.org/10.1002/cem.2616

Golubović J, Protić A, Zečević M, Otašević B, Mikić M. Artificial neural networks modeling in ultra performance liquid chromatography method optimization of mycophenolate mofetil and its degradation products. in Journal of Chemometrics. 2014;28(7):567-574.
doi:10.1002/cem.2616 .

Golubović, Jelena, Protić, Ana, Zečević, Mira, Otašević, Biljana, Mikić, Marija, "Artificial neural networks modeling in ultra performance liquid chromatography method optimization of mycophenolate mofetil and its degradation products" in Journal of Chemometrics, 28, no. 7 (2014):567-574,
https://doi.org/10.1002/cem.2616 . .

TY  - JOUR
AU  - Protić, Ana
AU  - Otašević, Biljana
AU  - Golubović, Jelena
AU  - Zečević, Mira
AU  - Živanović, Ljiljana
AU  - Vekić, Jelena
AU  - Zeljković, Aleksandra
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1809
AB  - Purification of biological matrix prior to HPLC analysis has been complex procedure and source of great variability of analytical results. The most used biological matrixes used for analysis are plasma, serum, urine and saliva and it has been advisable to use the simplest procedure for purification of these samples. Biological matrixes are complex and variability of its content is the main problem in development of bioanalytical methods. Namely, plasma and urine samples contain large number of endogenous compounds in concentrations much larger than concentration of investigated analyte. The concentrations of investigated analytes are often in very low concentrations and its structure can be very similar to structure of some endogenous compounds. Due to this problem, purification and concentration of biomatrix is one of the most important steps in development of bioanalytical methods. For bioanalytical methods the most important parameters are reliability and repeatability of the analytical results. Validation of bioanalytical chromatographic methods can be conducted according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), Food and Drug Administration (FDA) and European Medicines Agency (EMA). During the validation process selectivity, limit of detection (LOD), lower limits of quantification (LLOQ), range, linearity, precision, accuracy, stability and efficacy of biological sample purification have to be investigated.
AB  - Priprema biološkog materijala pre HPLC analize predstavlja kompleksnu proceduru koja je obično izvor velike varijabilnosti dobijenih analitičkih rezultata. Najčešće analizirane telesne tečnosti jesu plazma, serum, urin i saliva, i poželjno je primeniti što jednostavniju proceduru pri pripremi navedenih uzoraka. Kompleksnost i varijabilnost sastava biološkog materijala predstavlja jedan od glavnih problema u razvoju bioanalitičkih metoda. Plazma i urin sadrže veliki broj endogenih komponenata prisutnih u koncentracijama koje su obično veće od koncentacije samog leka i/ili njegovih metabolita. Osim što se lekovi i/ili njihovi metaboliti često nalaze u malim koncentracijama, njihova struktura može biti slična strukturi nekih endogenih komponenata. Imajući ovo u vidu, prečišćavanje i koncentrisanje biološkog materijala je jedan od najvažnijih koraka u razvoju bioanalitičke metode. Bez obzira sa kojim se uzorcima biološkog materijala radi, važno je voditi računa da se tokom analize dobiju pouzdani i ponovljivi rezultati. Validacija bioanalitičkih hromatografskih metoda izvodi se prema preporukama The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) regulative, Food and Drug Administration (FDA) i European Medicines Agency (EMA). U okviru postupka validacije ispituje se selektivnost, donja granica detekcije (LD), donja granica određivanja (eng. lower limits of quantification, LLOQ), opseg, linearnost, preciznost, tačnost, stabilnost i efikasnost postupka prečišćavanja uzoraka biološkog materijala.
PB  - Savez farmaceutskih udruženja Srbije, Beograd
T2  - Arhiv za farmaciju
T1  - Purification of biological samples and validation of bioanalytical HPLC methods for analysis of drugs and their metabolites
T1  - Priprema biološkog materijala i validacija bioanalitičkih HPLC metoda za ispitivanje lekova i njihovih metabolite
VL  - 62
IS  - 6
SP  - 576
EP  - 586
UR  - https://hdl.handle.net/21.15107/rcub_farfar_1809
ER  - 

@article{
author = "Protić, Ana and Otašević, Biljana and Golubović, Jelena and Zečević, Mira and Živanović, Ljiljana and Vekić, Jelena and Zeljković, Aleksandra",
year = "2012",
abstract = "Purification of biological matrix prior to HPLC analysis has been complex procedure and source of great variability of analytical results. The most used biological matrixes used for analysis are plasma, serum, urine and saliva and it has been advisable to use the simplest procedure for purification of these samples. Biological matrixes are complex and variability of its content is the main problem in development of bioanalytical methods. Namely, plasma and urine samples contain large number of endogenous compounds in concentrations much larger than concentration of investigated analyte. The concentrations of investigated analytes are often in very low concentrations and its structure can be very similar to structure of some endogenous compounds. Due to this problem, purification and concentration of biomatrix is one of the most important steps in development of bioanalytical methods. For bioanalytical methods the most important parameters are reliability and repeatability of the analytical results. Validation of bioanalytical chromatographic methods can be conducted according to The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH), Food and Drug Administration (FDA) and European Medicines Agency (EMA). During the validation process selectivity, limit of detection (LOD), lower limits of quantification (LLOQ), range, linearity, precision, accuracy, stability and efficacy of biological sample purification have to be investigated., Priprema biološkog materijala pre HPLC analize predstavlja kompleksnu proceduru koja je obično izvor velike varijabilnosti dobijenih analitičkih rezultata. Najčešće analizirane telesne tečnosti jesu plazma, serum, urin i saliva, i poželjno je primeniti što jednostavniju proceduru pri pripremi navedenih uzoraka. Kompleksnost i varijabilnost sastava biološkog materijala predstavlja jedan od glavnih problema u razvoju bioanalitičkih metoda. Plazma i urin sadrže veliki broj endogenih komponenata prisutnih u koncentracijama koje su obično veće od koncentacije samog leka i/ili njegovih metabolita. Osim što se lekovi i/ili njihovi metaboliti često nalaze u malim koncentracijama, njihova struktura može biti slična strukturi nekih endogenih komponenata. Imajući ovo u vidu, prečišćavanje i koncentrisanje biološkog materijala je jedan od najvažnijih koraka u razvoju bioanalitičke metode. Bez obzira sa kojim se uzorcima biološkog materijala radi, važno je voditi računa da se tokom analize dobiju pouzdani i ponovljivi rezultati. Validacija bioanalitičkih hromatografskih metoda izvodi se prema preporukama The International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) regulative, Food and Drug Administration (FDA) i European Medicines Agency (EMA). U okviru postupka validacije ispituje se selektivnost, donja granica detekcije (LD), donja granica određivanja (eng. lower limits of quantification, LLOQ), opseg, linearnost, preciznost, tačnost, stabilnost i efikasnost postupka prečišćavanja uzoraka biološkog materijala.",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Purification of biological samples and validation of bioanalytical HPLC methods for analysis of drugs and their metabolites, Priprema biološkog materijala i validacija bioanalitičkih HPLC metoda za ispitivanje lekova i njihovih metabolite",
volume = "62",
number = "6",
pages = "576-586",
url = "https://hdl.handle.net/21.15107/rcub_farfar_1809"
}

Protić, A., Otašević, B., Golubović, J., Zečević, M., Živanović, L., Vekić, J.,& Zeljković, A.. (2012). Purification of biological samples and validation of bioanalytical HPLC methods for analysis of drugs and their metabolites. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 62(6), 576-586.
https://hdl.handle.net/21.15107/rcub_farfar_1809

Protić A, Otašević B, Golubović J, Zečević M, Živanović L, Vekić J, Zeljković A. Purification of biological samples and validation of bioanalytical HPLC methods for analysis of drugs and their metabolites. in Arhiv za farmaciju. 2012;62(6):576-586.
https://hdl.handle.net/21.15107/rcub_farfar_1809 .

Protić, Ana, Otašević, Biljana, Golubović, Jelena, Zečević, Mira, Živanović, Ljiljana, Vekić, Jelena, Zeljković, Aleksandra, "Purification of biological samples and validation of bioanalytical HPLC methods for analysis of drugs and their metabolites" in Arhiv za farmaciju, 62, no. 6 (2012):576-586,
https://hdl.handle.net/21.15107/rcub_farfar_1809 .

TY  - JOUR
AU  - Golubović, Jelena
AU  - Protić, Ana
AU  - Zečević, Mira
AU  - Otašević, Biljana
AU  - Mikić, Marija
AU  - Živanović, Ljiljana
PY  - 2012
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/1748
AB  - Artificial neural network (ANN) is a learning system based on a computational technique which can simulate the neurological processing ability of the human brain. It was employed for building of the quantitative structure-retention relationships (QSRRs) model of antifungal agents-imidazoles or triazoles by structure. Computed molecular descriptors together with the percentage of acetonitrile in mobile phase (v/v) and buffer pH, being the most influential HPLC factors, were used as network inputs, giving the retention factor as model output. The multilayer perceptron network with a 9-5-1 topology was trained by using the back propagation algorithm. Good correlation between experimentally obtained data and ones predicted by using QSRR-ANN on previously unseen data sets indicates good predictive ability of the model.
PB  - Elsevier Science BV, Amsterdam
T2  - Talanta
T1  - Quantitative structure retention relationships of azole antifungal agents in reversed-phase high performance liquid chromatography
VL  - 100
SP  - 329
EP  - 337
DO  - 10.1016/j.talanta.2012.07.071
ER  - 

@article{
author = "Golubović, Jelena and Protić, Ana and Zečević, Mira and Otašević, Biljana and Mikić, Marija and Živanović, Ljiljana",
year = "2012",
abstract = "Artificial neural network (ANN) is a learning system based on a computational technique which can simulate the neurological processing ability of the human brain. It was employed for building of the quantitative structure-retention relationships (QSRRs) model of antifungal agents-imidazoles or triazoles by structure. Computed molecular descriptors together with the percentage of acetonitrile in mobile phase (v/v) and buffer pH, being the most influential HPLC factors, were used as network inputs, giving the retention factor as model output. The multilayer perceptron network with a 9-5-1 topology was trained by using the back propagation algorithm. Good correlation between experimentally obtained data and ones predicted by using QSRR-ANN on previously unseen data sets indicates good predictive ability of the model.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Talanta",
title = "Quantitative structure retention relationships of azole antifungal agents in reversed-phase high performance liquid chromatography",
volume = "100",
pages = "329-337",
doi = "10.1016/j.talanta.2012.07.071"
}

Golubović, J., Protić, A., Zečević, M., Otašević, B., Mikić, M.,& Živanović, L.. (2012). Quantitative structure retention relationships of azole antifungal agents in reversed-phase high performance liquid chromatography. in Talanta
Elsevier Science BV, Amsterdam., 100, 329-337.
https://doi.org/10.1016/j.talanta.2012.07.071

Golubović J, Protić A, Zečević M, Otašević B, Mikić M, Živanović L. Quantitative structure retention relationships of azole antifungal agents in reversed-phase high performance liquid chromatography. in Talanta. 2012;100:329-337.
doi:10.1016/j.talanta.2012.07.071 .

Golubović, Jelena, Protić, Ana, Zečević, Mira, Otašević, Biljana, Mikić, Marija, Živanović, Ljiljana, "Quantitative structure retention relationships of azole antifungal agents in reversed-phase high performance liquid chromatography" in Talanta, 100 (2012):329-337,
https://doi.org/10.1016/j.talanta.2012.07.071 . .