Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations

Link to this page

info:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172041/RS//

Development of molecules with antiinflammatory and cardioprotective activity: structural modifications, modelling, physicochemical characterization and formulation investigations (en)
Развој молекула са антиинфламаторним и кардиопроактивним дејством: структурне модификације, моделовање, физичкохемијска карактеризација и формулациона испитивања (sr)
Razvoj molekula sa antiinflamatornim i kardioproaktivnim dejstvom: strukturne modifikacije, modelovanje, fizičkohemijska karakterizacija i formulaciona ispitivanja (sr_RS)
Authors

Publications

Supplementary data for the article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213

Tubić, Biljana K.; Dobričić, Vladimir; Poljarević, Jelena; Savić, Aleksandar; Sabo, Tibor; Marković, Bojan D.

(Elsevier B.V., 2020)

TY  - DATA
AU  - Tubić, Biljana K.
AU  - Dobričić, Vladimir
AU  - Poljarević, Jelena
AU  - Savić, Aleksandar
AU  - Sabo, Tibor
AU  - Marković, Bojan D.
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3870
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Supplementary data for the article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213
UR  - https://hdl.handle.net/21.15107/rcub_cherry_3870
ER  - 
@misc{
author = "Tubić, Biljana K. and Dobričić, Vladimir and Poljarević, Jelena and Savić, Aleksandar and Sabo, Tibor and Marković, Bojan D.",
year = "2020",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Supplementary data for the article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213",
url = "https://hdl.handle.net/21.15107/rcub_cherry_3870"
}
Tubić, B. K., Dobričić, V., Poljarević, J., Savić, A., Sabo, T.,& Marković, B. D.. (2020). Supplementary data for the article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V...
https://hdl.handle.net/21.15107/rcub_cherry_3870
Tubić BK, Dobričić V, Poljarević J, Savić A, Sabo T, Marković BD. Supplementary data for the article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213. in Journal of Pharmaceutical and Biomedical Analysis. 2020;.
https://hdl.handle.net/21.15107/rcub_cherry_3870 .
Tubić, Biljana K., Dobričić, Vladimir, Poljarević, Jelena, Savić, Aleksandar, Sabo, Tibor, Marković, Bojan D., "Supplementary data for the article: Tubić, B.; Dobričić, V.; Poljarević, J.; Savić, A.; Sabo, T.; Marković, B. Estimation of Passive Gastrointestinal Absorption and Membrane Retention Using PAMPA Test, Quantitative Structure-Permeability and Quantitative Structure-Retention Relationship Analyses of Ethylenediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid and 1,3-Propanediamine-N,N’-Di-2-(3-Cyclohexyl)Propanoic Acid Derivatives. Journal of Pharmaceutical and Biomedical Analysis 2020, 184. https://doi.org/10.1016/j.jpba.2020.113213" in Journal of Pharmaceutical and Biomedical Analysis (2020),
https://hdl.handle.net/21.15107/rcub_cherry_3870 .

Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives

Tubić, Biljana K.; Dobričić, Vladimir; Poljarević, Jelena; Savić, Aleksandar; Sabo, Tibor; Marković, Bojan D.

(Elsevier B.V., 2020)

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Dobričić, Vladimir
AU  - Poljarević, Jelena
AU  - Savić, Aleksandar
AU  - Sabo, Tibor
AU  - Marković, Bojan D.
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3868
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3869
AB  - Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives
VL  - 184
DO  - 10.1016/j.jpba.2020.113213
ER  - 
@article{
author = "Tubić, Biljana K. and Dobričić, Vladimir and Poljarević, Jelena and Savić, Aleksandar and Sabo, Tibor and Marković, Bojan D.",
year = "2020",
abstract = "Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives",
volume = "184",
doi = "10.1016/j.jpba.2020.113213"
}
Tubić, B. K., Dobričić, V., Poljarević, J., Savić, A., Sabo, T.,& Marković, B. D.. (2020). Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 184.
https://doi.org/10.1016/j.jpba.2020.113213
Tubić BK, Dobričić V, Poljarević J, Savić A, Sabo T, Marković BD. Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. in Journal of Pharmaceutical and Biomedical Analysis. 2020;184.
doi:10.1016/j.jpba.2020.113213 .
Tubić, Biljana K., Dobričić, Vladimir, Poljarević, Jelena, Savić, Aleksandar, Sabo, Tibor, Marković, Bojan D., "Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives" in Journal of Pharmaceutical and Biomedical Analysis, 184 (2020),
https://doi.org/10.1016/j.jpba.2020.113213 . .

Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives

Tubić, Biljana K.; Dobričić, Vladimir; Poljarević, Jelena; Savić, Aleksandar; Sabo, Tibor; Marković, Bojan D.

(Elsevier B.V., 2020)

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Dobričić, Vladimir
AU  - Poljarević, Jelena
AU  - Savić, Aleksandar
AU  - Sabo, Tibor
AU  - Marković, Bojan D.
PY  - 2020
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/3868
AB  - Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives
VL  - 184
DO  - 10.1016/j.jpba.2020.113213
ER  - 
@article{
author = "Tubić, Biljana K. and Dobričić, Vladimir and Poljarević, Jelena and Savić, Aleksandar and Sabo, Tibor and Marković, Bojan D.",
year = "2020",
abstract = "Passive gastrointestinal absorption and membrane retention of twelve esters of (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (EDCP) and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid (PDCP), as well as of these two non-esterified acids were estimated using PAMPA test. Artificial PAMPA membrane used in this study for the simulation of gastrointestinal barrier was solution of egg lecithin in dodecane (1 % w/v). All tested compounds belong to class III (high membrane retention and low permeation), whereas EDCP, dipentyl ester of PDCP (DPE-PDCP) and diisopentyl ester of PDCP (DIPE-PDCP) belong to class I (negligible membrane retention and low permeation). Finally, quantitative structure – permeability and structure – retention relationships models were created in order to find quantitative relationships between physico-chemical properties of tested compounds and PAMPA membrane permeability/membrane retention parameters. Statistically the most reliable models were analysed and used for the design of new compounds for which favourable membrane permeability and retention can be expected.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives",
volume = "184",
doi = "10.1016/j.jpba.2020.113213"
}
Tubić, B. K., Dobričić, V., Poljarević, J., Savić, A., Sabo, T.,& Marković, B. D.. (2020). Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 184.
https://doi.org/10.1016/j.jpba.2020.113213
Tubić BK, Dobričić V, Poljarević J, Savić A, Sabo T, Marković BD. Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. in Journal of Pharmaceutical and Biomedical Analysis. 2020;184.
doi:10.1016/j.jpba.2020.113213 .
Tubić, Biljana K., Dobričić, Vladimir, Poljarević, Jelena, Savić, Aleksandar, Sabo, Tibor, Marković, Bojan D., "Estimation of passive gastrointestinal absorption and membrane retention using PAMPA test, quantitative structure-permeability and quantitative structure-retention relationship analyses of ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives" in Journal of Pharmaceutical and Biomedical Analysis, 184 (2020),
https://doi.org/10.1016/j.jpba.2020.113213 . .

Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity

Tubić, Biljana K.; Vladimirov, Sandra S.; Marković, Bojan D.; Sabo, Tibor

(Slovensko Kemijsko Drustvo, Ljubljana, 2018)

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Vladimirov, Sandra S.
AU  - Marković, Bojan D.
AU  - Sabo, Tibor
PY  - 2018
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2113
AB  - O,O'-diethyl-(S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoate (DE-EDCP) is novel substance with cytotoxic activity in human leukemic cells. The aim of this study has been to predict in vivo bioavailability of the DE-EDCP and its potential metabolite (S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoic acid (EDCP) by in vitro characterization which includes determination of lipophilicity and passive membrane permeability. There has also been evaluated inter-laboratory reproducibility of the bio-analytical method which was previously developed and validated for non-clinical study of the DE-EDCP and EDCP. Distribution coefficient n-octanol/water was 1.68 and 0.03, and apparent permeability coefficient was 4 x 10(-4) cm/s and 20 x 10(-4) cm/s, for the DE-EDCP and EDCP, respectively. Observed results have shown that the DE-EDCP is more lipophilic with better membrane retention, but the EDCP has better pass through the membrane. Also, there has been demonstrated a reproducibility and robustness of the proposed bio-analytical method.
PB  - Slovensko Kemijsko Drustvo, Ljubljana
T2  - Acta Chimica Slovenica
T1  - Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity
VL  - 65
IS  - 1
SP  - 59
EP  - 64
DO  - 10.17344/acsi.2017.3477
ER  - 
@article{
author = "Tubić, Biljana K. and Vladimirov, Sandra S. and Marković, Bojan D. and Sabo, Tibor",
year = "2018",
abstract = "O,O'-diethyl-(S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoate (DE-EDCP) is novel substance with cytotoxic activity in human leukemic cells. The aim of this study has been to predict in vivo bioavailability of the DE-EDCP and its potential metabolite (S, S)-ethylenediamine-N, N'-di-2-(3-cyclohexyl) propanoic acid (EDCP) by in vitro characterization which includes determination of lipophilicity and passive membrane permeability. There has also been evaluated inter-laboratory reproducibility of the bio-analytical method which was previously developed and validated for non-clinical study of the DE-EDCP and EDCP. Distribution coefficient n-octanol/water was 1.68 and 0.03, and apparent permeability coefficient was 4 x 10(-4) cm/s and 20 x 10(-4) cm/s, for the DE-EDCP and EDCP, respectively. Observed results have shown that the DE-EDCP is more lipophilic with better membrane retention, but the EDCP has better pass through the membrane. Also, there has been demonstrated a reproducibility and robustness of the proposed bio-analytical method.",
publisher = "Slovensko Kemijsko Drustvo, Ljubljana",
journal = "Acta Chimica Slovenica",
title = "Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity",
volume = "65",
number = "1",
pages = "59-64",
doi = "10.17344/acsi.2017.3477"
}
Tubić, B. K., Vladimirov, S. S., Marković, B. D.,& Sabo, T.. (2018). Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity. in Acta Chimica Slovenica
Slovensko Kemijsko Drustvo, Ljubljana., 65(1), 59-64.
https://doi.org/10.17344/acsi.2017.3477
Tubić BK, Vladimirov SS, Marković BD, Sabo T. Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity. in Acta Chimica Slovenica. 2018;65(1):59-64.
doi:10.17344/acsi.2017.3477 .
Tubić, Biljana K., Vladimirov, Sandra S., Marković, Bojan D., Sabo, Tibor, "Prediction of in vivo Bioavailibility by in vitro Characterization of Ethylenediamine Dipropanoic Acid Derivatives with Cytotoxic Activity" in Acta Chimica Slovenica, 65, no. 1 (2018):59-64,
https://doi.org/10.17344/acsi.2017.3477 . .
1
2
2
1

Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum

Tubić, Biljana K.; Marković, Bojan D.; Vladimirov, Sandra S.; Ristić, Slavica M.; Ivković, Branka; Savić, Miroslav M.; Poljarević, Jelena; Sabo, Tibor

(Akademiai Kiado Rt, Budapest, 2017)

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Marković, Bojan D.
AU  - Vladimirov, Sandra S.
AU  - Ristić, Slavica M.
AU  - Ivković, Branka
AU  - Savić, Miroslav M.
AU  - Poljarević, Jelena
AU  - Sabo, Tibor
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2459
AB  - A series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum
VL  - 29
IS  - 2
SP  - 235
EP  - 252
DO  - 10.1556/1326.2017.29.2.7
ER  - 
@article{
author = "Tubić, Biljana K. and Marković, Bojan D. and Vladimirov, Sandra S. and Ristić, Slavica M. and Ivković, Branka and Savić, Miroslav M. and Poljarević, Jelena and Sabo, Tibor",
year = "2017",
abstract = "A series of new (S,S)-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate esters has shown cytotoxic activity towards human leukemic cell lines. The aim of this study was to develop and validate a bioanalytical method for quantification of (S,S)-O,O-diethyl-ethylenediamine-N,N'-di-2-(3-cyclohexyl)propanoate dihydrochlorides (DE-EDCP) and its metabolite, substituted propanoic acid (EDCP), in mouse serum by ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Structural analog, derivative of 1,3-propanediamine, was used as an internal standard (IS). Sample preparation employed protein precipitation by acetonitrile and subsequent centrifugation. Optimal UHPLC separation conditions were set to achieve simultaneous determination of both compounds in a short run time of 6 min. Additionally, the selected reaction monitoring (SRM) mode developed in this method allowed a highly sensitive, accurate, and precise identification of compounds of interest. The lower limit of quantitation (LOQ) was 1.3 ng mL(-1) for DE-EDCP and 0.3 mu g mL(-1) for EDCP. The calibration curves were linear over the concentration range of 1.3-26.7 ng mL(-1) and 0.3-6.7 mu g mL(-1) for DE-EDCP and EDCP, respectively. Precision (%CV) and accuracy (% RE) for DE-EDCP and EDCP ranged from 3.5% to 16.0% and from 1.8% to 14.4%, respectively. The validation process was performed in accordance with the regulatory guidance/guideline, and all of the obtained results met the established acceptance criteria. The newly developed and validated UHPLC-MS/MS method is rapid, sensitive, and selective, and it can be successfully applied to drug monitoring in nonclinical studies.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum",
volume = "29",
number = "2",
pages = "235-252",
doi = "10.1556/1326.2017.29.2.7"
}
Tubić, B. K., Marković, B. D., Vladimirov, S. S., Ristić, S. M., Ivković, B., Savić, M. M., Poljarević, J.,& Sabo, T.. (2017). Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 29(2), 235-252.
https://doi.org/10.1556/1326.2017.29.2.7
Tubić BK, Marković BD, Vladimirov SS, Ristić SM, Ivković B, Savić MM, Poljarević J, Sabo T. Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum. in Acta Chromatographica. 2017;29(2):235-252.
doi:10.1556/1326.2017.29.2.7 .
Tubić, Biljana K., Marković, Bojan D., Vladimirov, Sandra S., Ristić, Slavica M., Ivković, Branka, Savić, Miroslav M., Poljarević, Jelena, Sabo, Tibor, "Highly Sensitive UHPLC-MS/MS Method for Quantification of Ethylenediamine-N,N '-di-2-(3-cyclohexyl) Propanoic Acid Derivatives in Mouse Serum" in Acta Chromatographica, 29, no. 2 (2017):235-252,
https://doi.org/10.1556/1326.2017.29.2.7 . .
3
5
5
3

A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me

Tubić, Biljana K.; Marković, Bojan D.; Vladimirov, S.; Savic, S.; Poljarević, Jelena; Sabo, Tibor

(Govi-Verlag Pharmazeutischer Verlag Gmbh, Eschborn, 2017)

TY  - JOUR
AU  - Tubić, Biljana K.
AU  - Marković, Bojan D.
AU  - Vladimirov, S.
AU  - Savic, S.
AU  - Poljarević, Jelena
AU  - Sabo, Tibor
PY  - 2017
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2499
AB  - Fourteen compounds representing ester derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl) propanoic and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to determinate their lipophilicity data, and also to ensure a mathematical model for prediction lipophilicity data of potential in vivo metabolites and new derivatives of (S,S)-1,2-ethanediannine-N,N'-di-2-(3-cyclohexyl)propanoic acid, based on chromatographic parameters. Experimentally, lipophilicity data were obtained by a traditional shake flask procedure and an ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. A correlation between the partition coefficient n-octanol/water (logD(7,4)) and chromatographic data (CHI, phi(0)), and also, between logD(7,4) and retention time was investigated. A very good correlation (r(2)=0.8969) was found between lipophilicity parameters phi(0) and logD(7,4) obtained using UHPLC-MS and shake flask methods: logD(7,4) = (0.11 +/- 0.01)x phi(0) + (1.25 +/- 0.20)xN(c) - (9.19 +/- 1.18); statistical parameter F=47.84; significance of F = 3.74x10(-6), N-c=number of C atoms between two amino groups (N-c=2 for 1,2-ethanediamine derivatives and N-c=3 for 1,3-propanediamine derivatives).The model predictivity power was determined by cross validation leave one out (LOO) technique, and expressed by the term Q(2), was 0.89. The developed model has good predictivity power for prediction lipophilicity data of potential in vivo metabolites of the investigated compounds, such as novel 1,2-ethanediamine and 1,3-propanediamine N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. Also, the lipophilicity data obtained in the present study correlated with the antiproliferative activity of the investigated substances shown previously in in vitro studies.
PB  - Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn
T2  - Pharmazie
T1  - A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me
VL  - 72
IS  - 6
SP  - 317
EP  - 323
DO  - 10.1619/ph.2017.6208
ER  - 
@article{
author = "Tubić, Biljana K. and Marković, Bojan D. and Vladimirov, S. and Savic, S. and Poljarević, Jelena and Sabo, Tibor",
year = "2017",
abstract = "Fourteen compounds representing ester derivatives of (S,S)-1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl) propanoic and (S,S)-1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acids, expressing antiproliferative activity in vitro were examined. The objective of this study was to determinate their lipophilicity data, and also to ensure a mathematical model for prediction lipophilicity data of potential in vivo metabolites and new derivatives of (S,S)-1,2-ethanediannine-N,N'-di-2-(3-cyclohexyl)propanoic acid, based on chromatographic parameters. Experimentally, lipophilicity data were obtained by a traditional shake flask procedure and an ultra-high performance liquid chromatographic tandem mass spectrometry (UHPLC-MS) method. A correlation between the partition coefficient n-octanol/water (logD(7,4)) and chromatographic data (CHI, phi(0)), and also, between logD(7,4) and retention time was investigated. A very good correlation (r(2)=0.8969) was found between lipophilicity parameters phi(0) and logD(7,4) obtained using UHPLC-MS and shake flask methods: logD(7,4) = (0.11 +/- 0.01)x phi(0) + (1.25 +/- 0.20)xN(c) - (9.19 +/- 1.18); statistical parameter F=47.84; significance of F = 3.74x10(-6), N-c=number of C atoms between two amino groups (N-c=2 for 1,2-ethanediamine derivatives and N-c=3 for 1,3-propanediamine derivatives).The model predictivity power was determined by cross validation leave one out (LOO) technique, and expressed by the term Q(2), was 0.89. The developed model has good predictivity power for prediction lipophilicity data of potential in vivo metabolites of the investigated compounds, such as novel 1,2-ethanediamine and 1,3-propanediamine N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives. Also, the lipophilicity data obtained in the present study correlated with the antiproliferative activity of the investigated substances shown previously in in vitro studies.",
publisher = "Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn",
journal = "Pharmazie",
title = "A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me",
volume = "72",
number = "6",
pages = "317-323",
doi = "10.1619/ph.2017.6208"
}
Tubić, B. K., Marković, B. D., Vladimirov, S., Savic, S., Poljarević, J.,& Sabo, T.. (2017). A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me. in Pharmazie
Govi-Verlag  Pharmazeutischer Verlag Gmbh, Eschborn., 72(6), 317-323.
https://doi.org/10.1619/ph.2017.6208
Tubić BK, Marković BD, Vladimirov S, Savic S, Poljarević J, Sabo T. A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me. in Pharmazie. 2017;72(6):317-323.
doi:10.1619/ph.2017.6208 .
Tubić, Biljana K., Marković, Bojan D., Vladimirov, S., Savic, S., Poljarević, Jelena, Sabo, Tibor, "A new model to determine lipophilicity of 1,2-ethanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid and 1,3-propanediamine-N,N'-di-2-(3-cyclohexyl)propanoic acid derivatives with antiproliferative activity by combining shake flask procedure and UHPLC-MS me" in Pharmazie, 72, no. 6 (2017):317-323,
https://doi.org/10.1619/ph.2017.6208 . .
2
2
2

Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats

Crevar-Sakač, Milkica; Vujić, Zorica; Kotur-Stevuljević, Jelena; Ivanišević, Jasmina; Jelić-Ivanović, Zorana; Milenković, Marina; Markelic, Milica; Vujčić, Zoran

(Military Medical Acad-Ini, Belgrade, 2016)

TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Kotur-Stevuljević, Jelena
AU  - Ivanišević, Jasmina
AU  - Jelić-Ivanović, Zorana
AU  - Milenković, Marina
AU  - Markelic, Milica
AU  - Vujčić, Zoran
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2064
AB  - Backgroung/Aim. Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of well established antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. Methods. Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per as with atorvastatin (1.15 mg/kg body wright - b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. Results. The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde MDA, proxidative-antioxidative balance - PAB) and anti oxidative protection (reduced glutathione - GSH, paraoxanase 1 - PON1, superoxide dismutase - SODA SH groups), especially ALTINC was successful in oxidative status improvement. Conclusion. Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin.
AB  - Uvod/Cilj. Savremena istraživanja sve više se okreću mogućnosti kombinovanja konvencionalne terapije sa biljnim lekovitim proizvodima. Cilj ovog istraživanja bio je praćenje efekata atorvastatina (CAS broj 134523-00-5), poznatog leka koji se koristi u terapiji hiperlipidemije, i tinkture lista artičoke primenjenih pojedinačno, kao i u obliku kombinovane terapije. Metode. Eksperimentalne životinje bile su podeljene u pet grupa: grupa I bila je kontrolna i činili su je pacovi hranjeni standardnom hranom za glodare tokom 11 nedelja, dok su preostale četiri grupe (II-V) činili pacovi koji su hranjeni standardnom hranom tokom prve nedelje, a potom u narednih 10 hranom bogatom holesterolom. Grupa II nije dobijala nikakav tretman, dok su III, IV i V posle 4. nedelje od početka uzimanja hrane bogate holesterolom, tokom narednih šest nedelja tretirane per os, redom: atorvastatinom u dozi od 1,15 mg/kg, tinkturom artičoke u dozi od 0,1 mL/kg i njihovom kombinacijom u istim dozama. Rezultati. Hrana bogata holesterolom izazvala je uznapredovalu hiperholesterolemiju na koju terapija nije značajno delovala. Terapija je pokazala povoljan efekat na debljinu zida trbušne aorte, parametre oksidativnog stresa (malondialdehid - MDA, prooksidativni-antioksidativni balans - PAB) i anti-oksidativne zaštite (redukovani glutation - GSH, SH grupe, paraoksonazu1 - PON1, superoksid dismutazu - SOD). Tinktura lista artičoke pokazala se najboljom u poboljšanju oksidativnog statusa. Zaključak. Poređenje pojedinačne terapije pokazalo je da tinktura lista artičoke ima jako anti-oksidativno dejstvo i pokazuje povoljne efekte u početnim fazama aterosklerotskog procesa. S obzirom na to da atorvastatin i komponente tinkture lista artičoke verovatno deluju različitim mehanizmima, kombinovana primena može imati povoljne efekte, ali se mora dodatno ispitati jer dobijeni rezultati ukazuju da je tinktura lista artičoke manje efikasan kada se primenjuje zajedno sa atorvastatinom.
PB  - Military Medical Acad-Ini, Belgrade
T2  - Vojnosanitetski pregled
T1  - Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats
T1  - Uticaj atorvastatina i tinkture lista artičoke na oksidativni stres kod pacova sa hiperholesterolemijom
VL  - 73
IS  - 2
SP  - 178
EP  - 187
DO  - 10.2298/VSP140917148C
ER  - 
@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Kotur-Stevuljević, Jelena and Ivanišević, Jasmina and Jelić-Ivanović, Zorana and Milenković, Marina and Markelic, Milica and Vujčić, Zoran",
year = "2016",
abstract = "Backgroung/Aim. Since combining conventional drugs with herbal medicinal products is in current research focus and possible of great interest as therapy improvement way, the aim of this study was to determine the effects of well established antiatherosclerotic drug atorvastatin (CAS number 134523-00-5) and commercially available artichoke leaf tincture (ALTINC), used as combined therapy, as well as to compare effects of these two treatments separately. Methods. Experimental animals were divided into five groups: the group I (the control group of rats fed with standard diet during 11 weeks), and the remaining 4 groups of rats (II, III, IV and V) fed with standard diet during the first week and then with hypercholesterolemic diet during the next 10 weeks. The group II of rats were left without treatment, while in the groups III, IV and V were rats treated per as with atorvastatin (1.15 mg/kg body wright - b.w.), ALTINC (0.1 mL/kg b.w.) and their combination in same doses, respectively, for the last six weeks. Results. The cholesterol rich diet led to pronounced hyperlipidemia which could not be overcame with the therapy. However, the therapy showed positive effects on abdominal aorta wall thickness and parameters of oxidative stress (malondialdehyde MDA, proxidative-antioxidative balance - PAB) and anti oxidative protection (reduced glutathione - GSH, paraoxanase 1 - PON1, superoxide dismutase - SODA SH groups), especially ALTINC was successful in oxidative status improvement. Conclusion. Separate treatments comparison showed that artichoke leaf tincture is very potent antioxidant with beneficial effects in early stages of atherosclerosis. Since atorvastatin and constituents of ALTINC probably have different mechanisms of action, simultaneous use of both therapies could be beneficial but should be further investigated since our results showed that ALTINC is less effective when used in combination with atorvastatin., Uvod/Cilj. Savremena istraživanja sve više se okreću mogućnosti kombinovanja konvencionalne terapije sa biljnim lekovitim proizvodima. Cilj ovog istraživanja bio je praćenje efekata atorvastatina (CAS broj 134523-00-5), poznatog leka koji se koristi u terapiji hiperlipidemije, i tinkture lista artičoke primenjenih pojedinačno, kao i u obliku kombinovane terapije. Metode. Eksperimentalne životinje bile su podeljene u pet grupa: grupa I bila je kontrolna i činili su je pacovi hranjeni standardnom hranom za glodare tokom 11 nedelja, dok su preostale četiri grupe (II-V) činili pacovi koji su hranjeni standardnom hranom tokom prve nedelje, a potom u narednih 10 hranom bogatom holesterolom. Grupa II nije dobijala nikakav tretman, dok su III, IV i V posle 4. nedelje od početka uzimanja hrane bogate holesterolom, tokom narednih šest nedelja tretirane per os, redom: atorvastatinom u dozi od 1,15 mg/kg, tinkturom artičoke u dozi od 0,1 mL/kg i njihovom kombinacijom u istim dozama. Rezultati. Hrana bogata holesterolom izazvala je uznapredovalu hiperholesterolemiju na koju terapija nije značajno delovala. Terapija je pokazala povoljan efekat na debljinu zida trbušne aorte, parametre oksidativnog stresa (malondialdehid - MDA, prooksidativni-antioksidativni balans - PAB) i anti-oksidativne zaštite (redukovani glutation - GSH, SH grupe, paraoksonazu1 - PON1, superoksid dismutazu - SOD). Tinktura lista artičoke pokazala se najboljom u poboljšanju oksidativnog statusa. Zaključak. Poređenje pojedinačne terapije pokazalo je da tinktura lista artičoke ima jako anti-oksidativno dejstvo i pokazuje povoljne efekte u početnim fazama aterosklerotskog procesa. S obzirom na to da atorvastatin i komponente tinkture lista artičoke verovatno deluju različitim mehanizmima, kombinovana primena može imati povoljne efekte, ali se mora dodatno ispitati jer dobijeni rezultati ukazuju da je tinktura lista artičoke manje efikasan kada se primenjuje zajedno sa atorvastatinom.",
publisher = "Military Medical Acad-Ini, Belgrade",
journal = "Vojnosanitetski pregled",
title = "Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats, Uticaj atorvastatina i tinkture lista artičoke na oksidativni stres kod pacova sa hiperholesterolemijom",
volume = "73",
number = "2",
pages = "178-187",
doi = "10.2298/VSP140917148C"
}
Crevar-Sakač, M., Vujić, Z., Kotur-Stevuljević, J., Ivanišević, J., Jelić-Ivanović, Z., Milenković, M., Markelic, M.,& Vujčić, Z.. (2016). Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats. in Vojnosanitetski pregled
Military Medical Acad-Ini, Belgrade., 73(2), 178-187.
https://doi.org/10.2298/VSP140917148C
Crevar-Sakač M, Vujić Z, Kotur-Stevuljević J, Ivanišević J, Jelić-Ivanović Z, Milenković M, Markelic M, Vujčić Z. Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats. in Vojnosanitetski pregled. 2016;73(2):178-187.
doi:10.2298/VSP140917148C .
Crevar-Sakač, Milkica, Vujić, Zorica, Kotur-Stevuljević, Jelena, Ivanišević, Jasmina, Jelić-Ivanović, Zorana, Milenković, Marina, Markelic, Milica, Vujčić, Zoran, "Effects of atorvastatin and artichoke leaf tincture on oxidative stress in hypercholesterolemic rats" in Vojnosanitetski pregled, 73, no. 2 (2016):178-187,
https://doi.org/10.2298/VSP140917148C . .
1
12
3
11
8

LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma

Crevar-Sakač, Milkica; Vujić, Zorica; Vujčić, Zoran; Marković, Bojan D.; Vasiljević, Dragana

(Akademiai Kiado Rt, Budapest, 2016)

TY  - JOUR
AU  - Crevar-Sakač, Milkica
AU  - Vujić, Zorica
AU  - Vujčić, Zoran
AU  - Marković, Bojan D.
AU  - Vasiljević, Dragana
PY  - 2016
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2349
AB  - A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C-18 Analytical, 4.6 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt  Q3, collision energy) atorvastatin (559.47 - gt  440.03, 22 eV), atorvastatin lactone (541.36 - gt  448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt  440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt  440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL(-1) for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL(-1) for atorvastatin and atorvastatin lactone with excellent linearity (r(2)  gt = 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL(-1) for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL(-1) for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.
PB  - Akademiai Kiado Rt, Budapest
T2  - Acta Chromatographica
T1  - LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma
VL  - 28
IS  - 3
SP  - 281
EP  - 298
DO  - 10.1556/1326.2016.28.3.1
ER  - 
@article{
author = "Crevar-Sakač, Milkica and Vujić, Zorica and Vujčić, Zoran and Marković, Bojan D. and Vasiljević, Dragana",
year = "2016",
abstract = "A simple and sensitive liquid chromatography-tandem mass spectrometry method was developed for the quantification of atorvastatin, ortho-hydroxyatorvastatin, para-hydroxyatorvastatin, and atorvastatin lactone in rat plasma. Solid-phase extraction was used for preparation of samples. Rosuvastatin was chosen as an internal standard. Chromatographic separation was achieved on ZORBAX Eclipse C-18 Analytical, 4.6 x 100 mm (3.5 mu m) column with a gradient mobile phase composed of acetonitrile and 0.1% acetic acid, at a flow rate of 400 mu L min(-1). The column was kept at constant temperature (25 degrees C), and autosampler tray temperature was set at 4 degrees C. The following selected reaction monitoring (SRM) transitions were selected: (m/z, Q1 - gt  Q3, collision energy) atorvastatin (559.47 - gt  440.03, 22 eV), atorvastatin lactone (541.36 - gt  448.02, 19 eV), orthohydroxyatorvastatin (575.20 - gt  440.18, 20 eV), para-hydroxyatorvastatin (575.54 - gt  440.18, 20 eV), and rosuvastatin (482.25 with selected combination of two fragments 257.77, 31 eV, and 299.81, 35 eV) in positive ion mode. The method was validated over a concentration range of 0.5-20 ng mL(-1) for ortho-hydroxyatorvastatin and para-hydroxyatorvastatin and 0.1-20 ng mL(-1) for atorvastatin and atorvastatin lactone with excellent linearity (r(2)  gt = 0.99). This method demonstrated acceptable precision and accuracy at four quality control concentration levels. The detection limits were 0.1 and 0.13 ng mL(-1) for orthohydroxyatorvastatin and para-hydroxyatorvastatin, respectively, and 0.05 ng mL(-1) for atorvastatin and atorvastatin lactone. All analytes were found to be stable at examined conditions. Validated method was applied for determination of atorvastatin and its metabolites in plasma of experimental animals.",
publisher = "Akademiai Kiado Rt, Budapest",
journal = "Acta Chromatographica",
title = "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma",
volume = "28",
number = "3",
pages = "281-298",
doi = "10.1556/1326.2016.28.3.1"
}
Crevar-Sakač, M., Vujić, Z., Vujčić, Z., Marković, B. D.,& Vasiljević, D.. (2016). LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica
Akademiai Kiado Rt, Budapest., 28(3), 281-298.
https://doi.org/10.1556/1326.2016.28.3.1
Crevar-Sakač M, Vujić Z, Vujčić Z, Marković BD, Vasiljević D. LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma. in Acta Chromatographica. 2016;28(3):281-298.
doi:10.1556/1326.2016.28.3.1 .
Crevar-Sakač, Milkica, Vujić, Zorica, Vujčić, Zoran, Marković, Bojan D., Vasiljević, Dragana, "LC-MS/MS Method for Quantification of Atorvastatin, o-Hydroxyatorvastatin, p-Hydroxyatorvastatin, and Atorvastatin Lactone in Rat Plasma" in Acta Chromatographica, 28, no. 3 (2016):281-298,
https://doi.org/10.1556/1326.2016.28.3.1 . .
4
1
5
4