Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology
Authors
Jančić-Stojanović, Biljana
Vemić, Sava
Elezović, Valentina
Petrović, Ana
Sinadinović, Zoran
Ivanović, Darko
Damjanović, Svetozar S.
Miljković, Branislava

Article (Accepted Version)
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A simple and reliable new HPLC method with UV detection has been developed and validated for simultaneous determination of mitotane and its two metabolites DDA and DDE. Method development was carried out utilizing systematical approach of the design of experiments (DoE) methodology. For estimation of factors influence on selected chromatographic responses and definition of the optimal chromatographic conditions, Box-Behnken experimental design was applied. The defined optimal separation conditions were: column Restek Ultra Aqua C-18 with pre-column Restek Ultra Aqua C-18 operating at temperature 35 degrees C; mixture of acetonitrile and 0.5% formic acid as mobile phase with 1.2mL min(-1) flow rate and detection at 230nm. As sample preparation method, liquid-liquid extraction was chosen. Method was fully validated and LOQ and LOD were experimentally determined. Finally, method was successfully applied for determination of mitotane and its metabolites in plasma samples of patients with a...drenocortical carcinoma.
Keywords:
liquid chromatography / metabolites DDA and DDE / validation / experimental design / mitotaneSource:
Journal of Liquid Chromatography & Related Technologies, 2015, 38, 14, 1371-1378Publisher:
- Taylor & Francis Inc, Philadelphia
Funding / projects:
- Modelling of different chromatographic systems with chemometrical approach in pharmaceutical analysis (RS-172052)
Note:
- This is peer-reviewed version of the following article: Jancic-Stojanovic, B.; Vemić, S.; Elezović, V.; Petrović, A.; Sinadinović, Z.; Ivanović, D.; Damjanović, S.; Miljković, B. Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology. J. Liq. Chromatogr. Relat. Technol. 2015, 38 (14), 1371–1378. https://doi.org/10.1080/10826076.2015.1057645
DOI: 10.1080/10826076.2015.1057645
ISSN: 1082-6076
WoS: 000359492000003
Scopus: 2-s2.0-84938869801
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/2438https://farfar.pharmacy.bg.ac.rs/handle/123456789/3432
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Institution/Community
PharmacyTY - JOUR AU - Jančić-Stojanović, Biljana AU - Vemić, Sava AU - Elezović, Valentina AU - Petrović, Ana AU - Sinadinović, Zoran AU - Ivanović, Darko AU - Damjanović, Svetozar S. AU - Miljković, Branislava PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2438 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3432 AB - A simple and reliable new HPLC method with UV detection has been developed and validated for simultaneous determination of mitotane and its two metabolites DDA and DDE. Method development was carried out utilizing systematical approach of the design of experiments (DoE) methodology. For estimation of factors influence on selected chromatographic responses and definition of the optimal chromatographic conditions, Box-Behnken experimental design was applied. The defined optimal separation conditions were: column Restek Ultra Aqua C-18 with pre-column Restek Ultra Aqua C-18 operating at temperature 35 degrees C; mixture of acetonitrile and 0.5% formic acid as mobile phase with 1.2mL min(-1) flow rate and detection at 230nm. As sample preparation method, liquid-liquid extraction was chosen. Method was fully validated and LOQ and LOD were experimentally determined. Finally, method was successfully applied for determination of mitotane and its metabolites in plasma samples of patients with adrenocortical carcinoma. PB - Taylor & Francis Inc, Philadelphia T2 - Journal of Liquid Chromatography & Related Technologies T1 - Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology VL - 38 IS - 14 SP - 1371 EP - 1378 DO - 10.1080/10826076.2015.1057645 ER -
@article{ author = "Jančić-Stojanović, Biljana and Vemić, Sava and Elezović, Valentina and Petrović, Ana and Sinadinović, Zoran and Ivanović, Darko and Damjanović, Svetozar S. and Miljković, Branislava", year = "2015", abstract = "A simple and reliable new HPLC method with UV detection has been developed and validated for simultaneous determination of mitotane and its two metabolites DDA and DDE. Method development was carried out utilizing systematical approach of the design of experiments (DoE) methodology. For estimation of factors influence on selected chromatographic responses and definition of the optimal chromatographic conditions, Box-Behnken experimental design was applied. The defined optimal separation conditions were: column Restek Ultra Aqua C-18 with pre-column Restek Ultra Aqua C-18 operating at temperature 35 degrees C; mixture of acetonitrile and 0.5% formic acid as mobile phase with 1.2mL min(-1) flow rate and detection at 230nm. As sample preparation method, liquid-liquid extraction was chosen. Method was fully validated and LOQ and LOD were experimentally determined. Finally, method was successfully applied for determination of mitotane and its metabolites in plasma samples of patients with adrenocortical carcinoma.", publisher = "Taylor & Francis Inc, Philadelphia", journal = "Journal of Liquid Chromatography & Related Technologies", title = "Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology", volume = "38", number = "14", pages = "1371-1378", doi = "10.1080/10826076.2015.1057645" }
Jančić-Stojanović, B., Vemić, S., Elezović, V., Petrović, A., Sinadinović, Z., Ivanović, D., Damjanović, S. S.,& Miljković, B.. (2015). Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology. in Journal of Liquid Chromatography & Related Technologies Taylor & Francis Inc, Philadelphia., 38(14), 1371-1378. https://doi.org/10.1080/10826076.2015.1057645
Jančić-Stojanović B, Vemić S, Elezović V, Petrović A, Sinadinović Z, Ivanović D, Damjanović SS, Miljković B. Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology. in Journal of Liquid Chromatography & Related Technologies. 2015;38(14):1371-1378. doi:10.1080/10826076.2015.1057645 .
Jančić-Stojanović, Biljana, Vemić, Sava, Elezović, Valentina, Petrović, Ana, Sinadinović, Zoran, Ivanović, Darko, Damjanović, Svetozar S., Miljković, Branislava, "Development of New Liquid Chromatographic Method for Mitotane and Its Metabolites Determination in Human Plasma Employing Design of Experiments Methodology" in Journal of Liquid Chromatography & Related Technologies, 38, no. 14 (2015):1371-1378, https://doi.org/10.1080/10826076.2015.1057645 . .