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

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

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

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

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