The application of chromatography techniques for the purification process optimization of amide of hydrocortisone-derived cortienic acid and ethyl ester of L-glycine
Primena hromatografskih tehnika u optimizaciji procesa prečišćavanja amida kortienske kiseline iz hidrokortizona i etil estra L-glicina
Апстракт
Soft ('antedrug') glucocorticoids are pharmacologically active compounds which are biotransformed in a predictable and controllable way to inactive and non-toxic metabolites. Amides of cortienic acids (17(-carboxamide derivatives of glucocorticoids) are potential soft drugs with fewer side effects than traditional glucocorticoids. The purification of 17(- carboxamide derivatives of hydrocortisone was explained using the amide of hydrocortisonederived cortienic acid and ethyl ester of L-glycine as an example and performed by use of column chromatography and preparative thin-layer chromatography (TLC). The optimization of purification process was performed employing analytical TLC and reversed-phase highperformance liquid chromatography (RP-HPLC). The mobile phase that enables best chromatographic separation of the amide from impurities on TLC plate (chloroform-methanol (95:5 V/V)) was selected and modified (reduction of polarity and addition of glacial acetic acid) to be used for the co...lumn chromatography and preparative TLC purification. It was confirmed by use of RP-HPLC that purification procedures applied in this study resulted in pure (96.2 %) amide.
Soft ('antedrug') glukokortikoidi su farmakološki aktivna jedinjenja koja se biotransformišu na predvidiv i kontrolisan način do neaktivnih i netoksičnih metabolita. Amidi kortienskih kiselina (17(-karboksamidni derivati glukokortikoida) su potencijalni soft lekovi sa manje neželjenih efekata u odnosu na konvencionalne glukokortikoide. Prečišćavanje 17(- karboksamidnih derivata hidrokortizona je prikazano na primeru amida kortienske kiseline iz hidrokortizona i etil estra L-glicina i vrši se primenom hromatografije na koloni i preparativne tankoslojne hromatografije (TLC). Optimizacija procesa prečišćavanja je izvršena primenom analitičke TLC i reverzno-fazne tečne hromatografije pod visokim pritiskom (RP-HPLC). Mobilna faza koja omogućuje najbolje hromatografsko razdvajanje amida od nečistoća na TLC pločici (hloroform-metanol (95:5 V/V) je odabrana i izvršena je njena modifikacija (smanjenje polarnosti, odnosno dodatak glacijalne sirćetne kliseline) u cilju prečišćavanja hromatografij...om na koloni, odnosno preparativnom TLC. Primenom RP-HPLC je potvrđeno da su navedeni postupci prečišćavanja omogućili dobijanje amida stepena čistoće 96,2 %.
Кључне речи:
17(-carboxamide derivatives of hydrocortisone / analytical TLC / RP-HPLC / column chromatography / preparative TLC / 17(-karboksamidni derivati hidrokortizona / analitička TLC / RP-HPLC / hromatografija na koloni / preparativna TLCИзвор:
Arhiv za farmaciju, 2014, 64, 3, 220-229Издавач:
- Savez farmaceutskih udruženja Srbije, Beograd
Финансирање / пројекти:
- Развој молекула са антиинфламаторним и кардиопроактивним дејством: структурне модификације, моделовање, физичкохемијска карактеризација и формулациона испитивања (RS-MESTD-Basic Research (BR or ON)-172041)
Институција/група
PharmacyTY - JOUR AU - Dobričić, Vladimir AU - Vladimirov, Sote AU - Čudina, Olivera PY - 2014 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2283 AB - Soft ('antedrug') glucocorticoids are pharmacologically active compounds which are biotransformed in a predictable and controllable way to inactive and non-toxic metabolites. Amides of cortienic acids (17(-carboxamide derivatives of glucocorticoids) are potential soft drugs with fewer side effects than traditional glucocorticoids. The purification of 17(- carboxamide derivatives of hydrocortisone was explained using the amide of hydrocortisonederived cortienic acid and ethyl ester of L-glycine as an example and performed by use of column chromatography and preparative thin-layer chromatography (TLC). The optimization of purification process was performed employing analytical TLC and reversed-phase highperformance liquid chromatography (RP-HPLC). The mobile phase that enables best chromatographic separation of the amide from impurities on TLC plate (chloroform-methanol (95:5 V/V)) was selected and modified (reduction of polarity and addition of glacial acetic acid) to be used for the column chromatography and preparative TLC purification. It was confirmed by use of RP-HPLC that purification procedures applied in this study resulted in pure (96.2 %) amide. AB - Soft ('antedrug') glukokortikoidi su farmakološki aktivna jedinjenja koja se biotransformišu na predvidiv i kontrolisan način do neaktivnih i netoksičnih metabolita. Amidi kortienskih kiselina (17(-karboksamidni derivati glukokortikoida) su potencijalni soft lekovi sa manje neželjenih efekata u odnosu na konvencionalne glukokortikoide. Prečišćavanje 17(- karboksamidnih derivata hidrokortizona je prikazano na primeru amida kortienske kiseline iz hidrokortizona i etil estra L-glicina i vrši se primenom hromatografije na koloni i preparativne tankoslojne hromatografije (TLC). Optimizacija procesa prečišćavanja je izvršena primenom analitičke TLC i reverzno-fazne tečne hromatografije pod visokim pritiskom (RP-HPLC). Mobilna faza koja omogućuje najbolje hromatografsko razdvajanje amida od nečistoća na TLC pločici (hloroform-metanol (95:5 V/V) je odabrana i izvršena je njena modifikacija (smanjenje polarnosti, odnosno dodatak glacijalne sirćetne kliseline) u cilju prečišćavanja hromatografijom na koloni, odnosno preparativnom TLC. Primenom RP-HPLC je potvrđeno da su navedeni postupci prečišćavanja omogućili dobijanje amida stepena čistoće 96,2 %. PB - Savez farmaceutskih udruženja Srbije, Beograd T2 - Arhiv za farmaciju T1 - The application of chromatography techniques for the purification process optimization of amide of hydrocortisone-derived cortienic acid and ethyl ester of L-glycine T1 - Primena hromatografskih tehnika u optimizaciji procesa prečišćavanja amida kortienske kiseline iz hidrokortizona i etil estra L-glicina VL - 64 IS - 3 SP - 220 EP - 229 DO - 10.5937/arhfarm1403220D ER -
@article{ author = "Dobričić, Vladimir and Vladimirov, Sote and Čudina, Olivera", year = "2014", abstract = "Soft ('antedrug') glucocorticoids are pharmacologically active compounds which are biotransformed in a predictable and controllable way to inactive and non-toxic metabolites. Amides of cortienic acids (17(-carboxamide derivatives of glucocorticoids) are potential soft drugs with fewer side effects than traditional glucocorticoids. The purification of 17(- carboxamide derivatives of hydrocortisone was explained using the amide of hydrocortisonederived cortienic acid and ethyl ester of L-glycine as an example and performed by use of column chromatography and preparative thin-layer chromatography (TLC). The optimization of purification process was performed employing analytical TLC and reversed-phase highperformance liquid chromatography (RP-HPLC). The mobile phase that enables best chromatographic separation of the amide from impurities on TLC plate (chloroform-methanol (95:5 V/V)) was selected and modified (reduction of polarity and addition of glacial acetic acid) to be used for the column chromatography and preparative TLC purification. It was confirmed by use of RP-HPLC that purification procedures applied in this study resulted in pure (96.2 %) amide., Soft ('antedrug') glukokortikoidi su farmakološki aktivna jedinjenja koja se biotransformišu na predvidiv i kontrolisan način do neaktivnih i netoksičnih metabolita. Amidi kortienskih kiselina (17(-karboksamidni derivati glukokortikoida) su potencijalni soft lekovi sa manje neželjenih efekata u odnosu na konvencionalne glukokortikoide. Prečišćavanje 17(- karboksamidnih derivata hidrokortizona je prikazano na primeru amida kortienske kiseline iz hidrokortizona i etil estra L-glicina i vrši se primenom hromatografije na koloni i preparativne tankoslojne hromatografije (TLC). Optimizacija procesa prečišćavanja je izvršena primenom analitičke TLC i reverzno-fazne tečne hromatografije pod visokim pritiskom (RP-HPLC). Mobilna faza koja omogućuje najbolje hromatografsko razdvajanje amida od nečistoća na TLC pločici (hloroform-metanol (95:5 V/V) je odabrana i izvršena je njena modifikacija (smanjenje polarnosti, odnosno dodatak glacijalne sirćetne kliseline) u cilju prečišćavanja hromatografijom na koloni, odnosno preparativnom TLC. Primenom RP-HPLC je potvrđeno da su navedeni postupci prečišćavanja omogućili dobijanje amida stepena čistoće 96,2 %.", publisher = "Savez farmaceutskih udruženja Srbije, Beograd", journal = "Arhiv za farmaciju", title = "The application of chromatography techniques for the purification process optimization of amide of hydrocortisone-derived cortienic acid and ethyl ester of L-glycine, Primena hromatografskih tehnika u optimizaciji procesa prečišćavanja amida kortienske kiseline iz hidrokortizona i etil estra L-glicina", volume = "64", number = "3", pages = "220-229", doi = "10.5937/arhfarm1403220D" }
Dobričić, V., Vladimirov, S.,& Čudina, O.. (2014). The application of chromatography techniques for the purification process optimization of amide of hydrocortisone-derived cortienic acid and ethyl ester of L-glycine. in Arhiv za farmaciju Savez farmaceutskih udruženja Srbije, Beograd., 64(3), 220-229. https://doi.org/10.5937/arhfarm1403220D
Dobričić V, Vladimirov S, Čudina O. The application of chromatography techniques for the purification process optimization of amide of hydrocortisone-derived cortienic acid and ethyl ester of L-glycine. in Arhiv za farmaciju. 2014;64(3):220-229. doi:10.5937/arhfarm1403220D .
Dobričić, Vladimir, Vladimirov, Sote, Čudina, Olivera, "The application of chromatography techniques for the purification process optimization of amide of hydrocortisone-derived cortienic acid and ethyl ester of L-glycine" in Arhiv za farmaciju, 64, no. 3 (2014):220-229, https://doi.org/10.5937/arhfarm1403220D . .