TY  - JOUR
AU  - Nikolić, N
AU  - Veselinović, D
AU  - Vladimirov, S
AU  - Karljiković-Rajić, Katarina
AU  - Lingeman, H
PY  - 2004
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/534
AB  - Tc-99m(V)-d,l-HM-PAO complex is well-known radiopharmaceutical for regional cerebral blood flow imaging. The proposed modifications in exametazime, hexamethylpropyleneamine oxime (HM-PAO) (4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime) synthesis, for reduction of intermediary reactant diiminebisoxime (DI) (4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime) concerned two reductants (NaBH4 and KBH4), two solvents (ethanol and 2-propanol), and three mole ratios of reactant/reductants (1:1, 1:1.5, and 1:2). The simultaneous analysis of diastereo-enantiomeric HM-PAO content, as well as the content of starting DI, in different reduction mixtures were pet-formed using chiral ligand-exchange chromatography (CLEC). The separation of the samples of investigated reduction mixtures, obtained in the second step of HM-PAO synthesis, has been accomplished by using an achiral sorbent (RP- 18) and a chiral mobile phase (CMP) containing copper(II) complex with N,N-ditnethyl-L-phenylalanine (L-DM-PhA) as initial complex for CLEC. With 12 different reduction conditions, the obtained ratios of diastereoisomers d,l-HM-PAO: mesa-HM-PAO varied from 69.2:30.8 to 15.9:84.1, in comparison to the reduction in routine synthesis of HM-PAO which gives an equal mixture of diastereoisomers. The ternary mixed complexes formation recorded spectrophotometrically on addition of HM-PAO or DI to the mobile phase with binary complex Cu(L-DM-PhA)(2), due to the evidence of bathochromic shift of 46 nm for lambda(max) with significant difference in absorptivity contributes to separation mechanism.
PB  - Elsevier Science BV, Amsterdam
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity
VL  - 34
IS  - 2
SP  - 285
EP  - 293
DO  - 10.1016/S0731-7085(03)00551-X
ER  - 

@article{
author = "Nikolić, N and Veselinović, D and Vladimirov, S and Karljiković-Rajić, Katarina and Lingeman, H",
year = "2004",
abstract = "Tc-99m(V)-d,l-HM-PAO complex is well-known radiopharmaceutical for regional cerebral blood flow imaging. The proposed modifications in exametazime, hexamethylpropyleneamine oxime (HM-PAO) (4,8-diaza-3,6,6,9-tetramethylundecane-2,10-dione bisoxime) synthesis, for reduction of intermediary reactant diiminebisoxime (DI) (4,8-diaza-3,6,6,9-tetramethylundecane-3,8-diene-2,10-dione bisoxime) concerned two reductants (NaBH4 and KBH4), two solvents (ethanol and 2-propanol), and three mole ratios of reactant/reductants (1:1, 1:1.5, and 1:2). The simultaneous analysis of diastereo-enantiomeric HM-PAO content, as well as the content of starting DI, in different reduction mixtures were pet-formed using chiral ligand-exchange chromatography (CLEC). The separation of the samples of investigated reduction mixtures, obtained in the second step of HM-PAO synthesis, has been accomplished by using an achiral sorbent (RP- 18) and a chiral mobile phase (CMP) containing copper(II) complex with N,N-ditnethyl-L-phenylalanine (L-DM-PhA) as initial complex for CLEC. With 12 different reduction conditions, the obtained ratios of diastereoisomers d,l-HM-PAO: mesa-HM-PAO varied from 69.2:30.8 to 15.9:84.1, in comparison to the reduction in routine synthesis of HM-PAO which gives an equal mixture of diastereoisomers. The ternary mixed complexes formation recorded spectrophotometrically on addition of HM-PAO or DI to the mobile phase with binary complex Cu(L-DM-PhA)(2), due to the evidence of bathochromic shift of 46 nm for lambda(max) with significant difference in absorptivity contributes to separation mechanism.",
publisher = "Elsevier Science BV, Amsterdam",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity",
volume = "34",
number = "2",
pages = "285-293",
doi = "10.1016/S0731-7085(03)00551-X"
}

Nikolić, N., Veselinović, D., Vladimirov, S., Karljiković-Rajić, K.,& Lingeman, H.. (2004). Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier Science BV, Amsterdam., 34(2), 285-293.
https://doi.org/10.1016/S0731-7085(03)00551-X

Nikolić N, Veselinović D, Vladimirov S, Karljiković-Rajić K, Lingeman H. Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity. in Journal of Pharmaceutical and Biomedical Analysis. 2004;34(2):285-293.
doi:10.1016/S0731-7085(03)00551-X .

Nikolić, N, Veselinović, D, Vladimirov, S, Karljiković-Rajić, Katarina, Lingeman, H, "Chiral ligand-exchange chromatography as the screening method for proposed modifications in exametazime synthesis to enhance diastereoselectivity" in Journal of Pharmaceutical and Biomedical Analysis, 34, no. 2 (2004):285-293,
https://doi.org/10.1016/S0731-7085(03)00551-X . .

TY  - 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 . .