Enantioselective Nano Liquid Chromatographic Separation of Racemic Pharmaceuticals

A Facile One-Pot In Situ Preparation of Lipase-Based Polymer Monoliths in Capillary Format

Marwa Ahmed, Ashraf GHANEM

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

New affinity monolithic capillary columns of 150 μm internal diameter were prepared in situ fused glass capillary via either immobilization or encapsulation of Candida antarctica lipase B (CALB) on or within polymer monoliths, respectively. The immobilized lipase-based monoliths were prepared via copolymerization of 19.1% monomers (8.9% MMA and 10.2% GMA), 19.8% EDMA, and 61.1% porogens (54.2% formamide and 6.9% 1-propanol) w/w or 20% GMA, 20% EDMA, and 60% porogens (51.6% cyclohexanol and 8.4% 1-dodecanol) in the presence of AIBN (1%) as a radical initiator. This was followed by pumping a solution of lipase through the capillaries and rinsing with potassium phosphate buffer. On the other hand, the encapsulated lipase-based monoliths were prepared via copolymerization of 20% monomers (GMA), 20% EDMA, and 60% porogens (48% 1-propanol, 6% 1,4-butanediol) or 16.4% monomers (16% BuMA, 0.4% SPMA), 23.6% EDMA, and 60% porogens (36% 1-propanol, 18% 1,4-butanediol along with 6% lipase aqueous solution in potassium phosphate buffer. The prepared capillary columns were investigated for the enantioselective nano liquid chromatographic separation of a set of different classes of racemic pharmaceuticals, namely, α- and β-blockers, antiinflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Run-to-run repeatability was quite satisfactory. The encapsulated lipase-based capillary monolith showed better enantioselective separations of most of the investigated compounds. Baseline separation was achieved for alprenolol, atenolol, bromoglutithimide, carbuterol, chloropheneramine, cizolertine carbinol, 4-hydroxy-3-methoxymandelic acid, desmethylcizolertine, nomifensine, normetanephrine, and sulconazole under reversed phase chromatographic conditions. A speculation about the understanding of the chiral recognition mechanism of lipase-based monoliths toward the investigated pharmaceuticals is discussed. 

Original languageEnglish
Pages (from-to)754-763
Number of pages10
JournalChirality
Volume26
Issue number11
DOIs
Publication statusPublished - 2014

Fingerprint

Lipases
Lipase
Drug products
Polymers
1-Propanol
Liquids
Pharmaceutical Preparations
Propanol
Monomers
Copolymerization
Buffers
Dodecanol
Potassium
Cyclohexanols
Dopamine Uptake Inhibitors
Normetanephrine
Alprenolol
Vanilmandelic Acid
Nomifensine
Phosphates

Cite this

@article{a2024b1a62d34366a0ac15136e7942e9,
title = "Enantioselective Nano Liquid Chromatographic Separation of Racemic Pharmaceuticals: A Facile One-Pot In Situ Preparation of Lipase-Based Polymer Monoliths in Capillary Format",
abstract = "New affinity monolithic capillary columns of 150 μm internal diameter were prepared in situ fused glass capillary via either immobilization or encapsulation of Candida antarctica lipase B (CALB) on or within polymer monoliths, respectively. The immobilized lipase-based monoliths were prepared via copolymerization of 19.1{\%} monomers (8.9{\%} MMA and 10.2{\%} GMA), 19.8{\%} EDMA, and 61.1{\%} porogens (54.2{\%} formamide and 6.9{\%} 1-propanol) w/w or 20{\%} GMA, 20{\%} EDMA, and 60{\%} porogens (51.6{\%} cyclohexanol and 8.4{\%} 1-dodecanol) in the presence of AIBN (1{\%}) as a radical initiator. This was followed by pumping a solution of lipase through the capillaries and rinsing with potassium phosphate buffer. On the other hand, the encapsulated lipase-based monoliths were prepared via copolymerization of 20{\%} monomers (GMA), 20{\%} EDMA, and 60{\%} porogens (48{\%} 1-propanol, 6{\%} 1,4-butanediol) or 16.4{\%} monomers (16{\%} BuMA, 0.4{\%} SPMA), 23.6{\%} EDMA, and 60{\%} porogens (36{\%} 1-propanol, 18{\%} 1,4-butanediol along with 6{\%} lipase aqueous solution in potassium phosphate buffer. The prepared capillary columns were investigated for the enantioselective nano liquid chromatographic separation of a set of different classes of racemic pharmaceuticals, namely, α- and β-blockers, antiinflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Run-to-run repeatability was quite satisfactory. The encapsulated lipase-based capillary monolith showed better enantioselective separations of most of the investigated compounds. Baseline separation was achieved for alprenolol, atenolol, bromoglutithimide, carbuterol, chloropheneramine, cizolertine carbinol, 4-hydroxy-3-methoxymandelic acid, desmethylcizolertine, nomifensine, normetanephrine, and sulconazole under reversed phase chromatographic conditions. A speculation about the understanding of the chiral recognition mechanism of lipase-based monoliths toward the investigated pharmaceuticals is discussed. ",
keywords = "enantioselective-separation, nano-liquid-chromatography, polymer-monolith, lipase, protein-encapsulation, Protein encapsulation, Nano liquid chromatography, Enantioselective separation, Polymer monolith, Lipase",
author = "Marwa Ahmed and Ashraf GHANEM",
year = "2014",
doi = "10.1002/chir.22290",
language = "English",
volume = "26",
pages = "754--763",
journal = "Chirality",
issn = "0899-0042",
publisher = "Wiley-Liss Inc.",
number = "11",

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TY - JOUR

T1 - Enantioselective Nano Liquid Chromatographic Separation of Racemic Pharmaceuticals

T2 - A Facile One-Pot In Situ Preparation of Lipase-Based Polymer Monoliths in Capillary Format

AU - Ahmed, Marwa

AU - GHANEM, Ashraf

PY - 2014

Y1 - 2014

N2 - New affinity monolithic capillary columns of 150 μm internal diameter were prepared in situ fused glass capillary via either immobilization or encapsulation of Candida antarctica lipase B (CALB) on or within polymer monoliths, respectively. The immobilized lipase-based monoliths were prepared via copolymerization of 19.1% monomers (8.9% MMA and 10.2% GMA), 19.8% EDMA, and 61.1% porogens (54.2% formamide and 6.9% 1-propanol) w/w or 20% GMA, 20% EDMA, and 60% porogens (51.6% cyclohexanol and 8.4% 1-dodecanol) in the presence of AIBN (1%) as a radical initiator. This was followed by pumping a solution of lipase through the capillaries and rinsing with potassium phosphate buffer. On the other hand, the encapsulated lipase-based monoliths were prepared via copolymerization of 20% monomers (GMA), 20% EDMA, and 60% porogens (48% 1-propanol, 6% 1,4-butanediol) or 16.4% monomers (16% BuMA, 0.4% SPMA), 23.6% EDMA, and 60% porogens (36% 1-propanol, 18% 1,4-butanediol along with 6% lipase aqueous solution in potassium phosphate buffer. The prepared capillary columns were investigated for the enantioselective nano liquid chromatographic separation of a set of different classes of racemic pharmaceuticals, namely, α- and β-blockers, antiinflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Run-to-run repeatability was quite satisfactory. The encapsulated lipase-based capillary monolith showed better enantioselective separations of most of the investigated compounds. Baseline separation was achieved for alprenolol, atenolol, bromoglutithimide, carbuterol, chloropheneramine, cizolertine carbinol, 4-hydroxy-3-methoxymandelic acid, desmethylcizolertine, nomifensine, normetanephrine, and sulconazole under reversed phase chromatographic conditions. A speculation about the understanding of the chiral recognition mechanism of lipase-based monoliths toward the investigated pharmaceuticals is discussed. 

AB - New affinity monolithic capillary columns of 150 μm internal diameter were prepared in situ fused glass capillary via either immobilization or encapsulation of Candida antarctica lipase B (CALB) on or within polymer monoliths, respectively. The immobilized lipase-based monoliths were prepared via copolymerization of 19.1% monomers (8.9% MMA and 10.2% GMA), 19.8% EDMA, and 61.1% porogens (54.2% formamide and 6.9% 1-propanol) w/w or 20% GMA, 20% EDMA, and 60% porogens (51.6% cyclohexanol and 8.4% 1-dodecanol) in the presence of AIBN (1%) as a radical initiator. This was followed by pumping a solution of lipase through the capillaries and rinsing with potassium phosphate buffer. On the other hand, the encapsulated lipase-based monoliths were prepared via copolymerization of 20% monomers (GMA), 20% EDMA, and 60% porogens (48% 1-propanol, 6% 1,4-butanediol) or 16.4% monomers (16% BuMA, 0.4% SPMA), 23.6% EDMA, and 60% porogens (36% 1-propanol, 18% 1,4-butanediol along with 6% lipase aqueous solution in potassium phosphate buffer. The prepared capillary columns were investigated for the enantioselective nano liquid chromatographic separation of a set of different classes of racemic pharmaceuticals, namely, α- and β-blockers, antiinflammatory drugs, antifungal drugs, dopamine antagonists, norepinephrine-dopamine reuptake inhibitors, catecholamines, sedative hypnotics, diuretics, antihistaminics, anticancer drugs, and antiarrhythmic drugs. Run-to-run repeatability was quite satisfactory. The encapsulated lipase-based capillary monolith showed better enantioselective separations of most of the investigated compounds. Baseline separation was achieved for alprenolol, atenolol, bromoglutithimide, carbuterol, chloropheneramine, cizolertine carbinol, 4-hydroxy-3-methoxymandelic acid, desmethylcizolertine, nomifensine, normetanephrine, and sulconazole under reversed phase chromatographic conditions. A speculation about the understanding of the chiral recognition mechanism of lipase-based monoliths toward the investigated pharmaceuticals is discussed. 

KW - enantioselective-separation

KW - nano-liquid-chromatography

KW - polymer-monolith

KW - lipase

KW - protein-encapsulation

KW - Protein encapsulation

KW - Nano liquid chromatography

KW - Enantioselective separation

KW - Polymer monolith

KW - Lipase

UR - http://www.scopus.com/inward/record.url?scp=84910119363&partnerID=8YFLogxK

UR - http://www.mendeley.com/research/enantioselective-nano-liquid-chromatographic-separation-racemic-pharmaceuticals-facile-onepot-situ-p

U2 - 10.1002/chir.22290

DO - 10.1002/chir.22290

M3 - Article

VL - 26

SP - 754

EP - 763

JO - Chirality

JF - Chirality

SN - 0899-0042

IS - 11

ER -