Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime
Abstract
The diastereo-enantio separation of isomeric mixtures of exametazime (HM-PAO) by liquid chromatography is described using an achiral sorbent (RP-18). A chiral eluent with the initial complex of Cu(II) and the optically active selector N,N-dimethyl-l-phenylalanine (l-DM-PhA), based on the ligand-exchange principle, has been applied. The separation is based on the presence of the immobilized binary complex Cu(l-DM-PhA)(2) and formation of mixed ternary complex. The optimal mole ratio of Cu(II):l-DM-PhA is 1:4, the pH should be between 4.1 and 4.2 and up to 0.8 mM of triethylamine is added for column presaturation with the initial complex. The elution order has been defined using isolated l-HM-PAO via l-HM-PAO L(+)tartrate and tneso-HM-PAO obtained by repeated recrystallization from the isomeric mixture of HM-PAO. Complete resolution between all isomers (R-S from 2.14 to 3.91) and partial resolution for meso(EE)/l-HM-PAO (R-S = 0.83) has been obtained. This means that the proposed chiral ...ligand-exchange chromatography (CLEC) can be used for determination of the isomeric purity of HM-PAO. This as an alternative method for resolution measurements with chiral columns.
Keywords:
column liquid chromatography / ligand-exchange chromatography / chiral separation / exametazime (HM-PAO)Source:
Journal of Pharmaceutical and Biomedical Analysis, 2003, 32, 6, 1159-1166Publisher:
- Pergamon-Elsevier Science Ltd, Oxford
DOI: 10.1016/S0731-7085(03)00230-9
ISSN: 0731-7085
PubMed: 12907259
WoS: 000185148800007
Scopus: 2-s2.0-0043205804
Collections
Institution/Community
PharmacyTY - JOUR AU - Nikolić, N AU - Veselinović, D AU - Vucina, J AU - Lingeman, H AU - Karljiković-Rajić, Katarina PY - 2003 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/436 AB - The diastereo-enantio separation of isomeric mixtures of exametazime (HM-PAO) by liquid chromatography is described using an achiral sorbent (RP-18). A chiral eluent with the initial complex of Cu(II) and the optically active selector N,N-dimethyl-l-phenylalanine (l-DM-PhA), based on the ligand-exchange principle, has been applied. The separation is based on the presence of the immobilized binary complex Cu(l-DM-PhA)(2) and formation of mixed ternary complex. The optimal mole ratio of Cu(II):l-DM-PhA is 1:4, the pH should be between 4.1 and 4.2 and up to 0.8 mM of triethylamine is added for column presaturation with the initial complex. The elution order has been defined using isolated l-HM-PAO via l-HM-PAO L(+)tartrate and tneso-HM-PAO obtained by repeated recrystallization from the isomeric mixture of HM-PAO. Complete resolution between all isomers (R-S from 2.14 to 3.91) and partial resolution for meso(EE)/l-HM-PAO (R-S = 0.83) has been obtained. This means that the proposed chiral ligand-exchange chromatography (CLEC) can be used for determination of the isomeric purity of HM-PAO. This as an alternative method for resolution measurements with chiral columns. PB - Pergamon-Elsevier Science Ltd, Oxford T2 - Journal of Pharmaceutical and Biomedical Analysis T1 - Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime VL - 32 IS - 6 SP - 1159 EP - 1166 DO - 10.1016/S0731-7085(03)00230-9 ER -
@article{ author = "Nikolić, N and Veselinović, D and Vucina, J and Lingeman, H and Karljiković-Rajić, Katarina", year = "2003", abstract = "The diastereo-enantio separation of isomeric mixtures of exametazime (HM-PAO) by liquid chromatography is described using an achiral sorbent (RP-18). A chiral eluent with the initial complex of Cu(II) and the optically active selector N,N-dimethyl-l-phenylalanine (l-DM-PhA), based on the ligand-exchange principle, has been applied. The separation is based on the presence of the immobilized binary complex Cu(l-DM-PhA)(2) and formation of mixed ternary complex. The optimal mole ratio of Cu(II):l-DM-PhA is 1:4, the pH should be between 4.1 and 4.2 and up to 0.8 mM of triethylamine is added for column presaturation with the initial complex. The elution order has been defined using isolated l-HM-PAO via l-HM-PAO L(+)tartrate and tneso-HM-PAO obtained by repeated recrystallization from the isomeric mixture of HM-PAO. Complete resolution between all isomers (R-S from 2.14 to 3.91) and partial resolution for meso(EE)/l-HM-PAO (R-S = 0.83) has been obtained. This means that the proposed chiral ligand-exchange chromatography (CLEC) can be used for determination of the isomeric purity of HM-PAO. This as an alternative method for resolution measurements with chiral columns.", publisher = "Pergamon-Elsevier Science Ltd, Oxford", journal = "Journal of Pharmaceutical and Biomedical Analysis", title = "Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime", volume = "32", number = "6", pages = "1159-1166", doi = "10.1016/S0731-7085(03)00230-9" }
Nikolić, N., Veselinović, D., Vucina, J., Lingeman, H.,& Karljiković-Rajić, K.. (2003). Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime. in Journal of Pharmaceutical and Biomedical Analysis Pergamon-Elsevier Science Ltd, Oxford., 32(6), 1159-1166. https://doi.org/10.1016/S0731-7085(03)00230-9
Nikolić N, Veselinović D, Vucina J, Lingeman H, Karljiković-Rajić K. Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime. in Journal of Pharmaceutical and Biomedical Analysis. 2003;32(6):1159-1166. doi:10.1016/S0731-7085(03)00230-9 .
Nikolić, N, Veselinović, D, Vucina, J, Lingeman, H, Karljiković-Rajić, Katarina, "Chiral ligand-exchange chromatography for diastereo-enantio separation of exametazime" in Journal of Pharmaceutical and Biomedical Analysis, 32, no. 6 (2003):1159-1166, https://doi.org/10.1016/S0731-7085(03)00230-9 . .