Type Of Organic Modifier Research Articles

Enantioselective separation of eight antihistamines with α1-acid glycoprotein-based chiral stationary phase by HPLC: Development and validation for the enantiomeric quality control

In the present paper, a sensitive and selective chiral LC method has been developed for enantiomeric separation and determination of eight antihistamines in pharmaceutical formulations. Enantiomeric separation was achieved on the α1-acid glycoprotein-based chiral stationary phase known as Chiralpak AGP. The effects of the mobile phase composition, type and proportion of organic modifier and the concentration and pH of the buffer on retention and resolution were fully investigated. All enantiomers of target analytes were successfully separated with the mobile phase consisting of methanol and 10 mM ammonium acetate buffer, at a flow rate of 0.9 mL min−1. Calibration curve of each enantiomer was linear over the concentration range of 5.0–100 μg mL−1, with the correlation coefficient above 0.9990. The limits of detection and quantification were below 0.80 and 3.18 μg mL−1, respectively. The recoveries were in the range of 98.0–102.4% with the relative standard deviation lower than 2.88% for all enantiomers. The validated method was demonstrated to be suitable for the quality control of the enantiomeric composition of antihistamines present in pharmaceuticals. Finally, the proposed chiral LC method was applied to the determination of antihistamines enantiomers in commercially available tablets containing racemic mixtures of compounds. Quantitative results of the commercial tablets demonstrated that the difference between the declared and determined values did not exceed 1.45%, and chiral antihistamines drugs were present in the form of racemates.

Selectivity of the Separation of Isomeric Chlorogenic Acids under the Conditions of Reversed-Phase HPLC

The selectivity of the separation of isomeric chlorogenic acids often found in natural samples (3, 4, and 5-caffeoylquinic acids, 3CQA, 4CQA, and 5CQA, respectively) under the conditions of reversed-phase chromatography on stationary phases of different brands, Kromasil (C18, C8, and C4), Symmetry C18, Reprosil-Pur C18-AQ, Nucleosil RPC18, and Diasfer C18, is studied. The results obtained favor the retention mechanism with predominant surface adsorption. The change in the selectivity of separation of a pair of 5CQA and 4CQA correlates with a change in the activity of residual silanol groups. At their low activity, the order of elution 3CQA < 5CQA < 4CQA does not depend on the mode (isocratic or gradient), the type of organic modifier, and the addition of an acid (formic, orthophosphoric) to the mobile phase. With an increase in the activity of silanol groups, the separation of the pair of 5CQA and 4CQA deteriorates up to the inversion of retention times. A Kromasil 100-5C18 column (250 × 4.6 mm) was chosen for a reliable separation of three acids in plant samples (instant coffee, juice, and “Mate” tea).

Evaluation of an ionic liquid chiral selector based on clindamycin phosphate in capillary electrophoresis.

Recently, increasing attention has been given to the research on chiral ionic liquids (CILs) in chiral separation field; however, only a few literatures focus on the exploration of CILs as the sole chiral selector. In this study, an ionic liquid chiral selector based on antibiotic, namely tetramethylammonium clindamycin phosphate (TMA-CP), was originally synthesized and subsequently utilized for enantioseparation in capillary electrophoresis (CE). Remarkably improved separations of eight racemic analytes were achieved in TMA-CP system in contrast to the clindamycin phosphate (CP) system. The optimal separation conditions were determinated by systematic experiments on several crucial parameters including the type and proportion of organic modifier, CIL concentration, buffer pH, and applied voltage. Additionally, molecular modeling with AutoDock was applied to probe into the chiral recognition mechanism of the ionic liquid chiral selectors, which well corresponded with the experimental results. It is the first time that antibiotic-based ionic liquid was exploited as favorable sole chiral selector in CE, and this strategy has paved a new way for development of novel ionic liquids chiral selectors based on antibiotics. Graphical abstract.

Separation of ephedrine and pseudoephedrine enantiomers using a polysaccharide-based chiral column: A normal phase liquid chromatography-high-resolution mass spectrometry approach.

Chiral considerations are found to be very much relevant in various aspects of forensic toxicology and pharmacology. In forensics, it has become increasingly important to identify the chirality of doping agents to avoid legal arguments and challenges to the analytical findings. The scope of this study was to develop an liquid chromatography-mass spectrometry (LCMS) method for the enantiomeric separation of typical illicit drugs such as ephedrines (ie, 1S,2R(+)-ephedrine and 1R,2S(-)-ephedrine) and pseudoephedrine (ie, R,R(-)-pseudoephedrine and S,S(+)-pseudoephedrine) by using normal phase chiral liquid chromatography-high-resolution mass spectrometry technique. Results show that the Lux i-amylose-1 stationary phase has very broad and balancing-enantio-recognition properties towards ephedrine analogues, and this immobilized chiral stationary phase may offer a powerful tool for enantio-separation of different types of pharmaceuticals in the normal phase mode. The type of mobile phase and organic modifier used appear to have dramatic influences on separation quality. Since the developed method was able to detect and separate the enantiomers at very low levels (in pico grams), this method opens easy access for the unambiguous identification of these illicit drugs and can be used for the routine screening of the biological samples in the antidoping laboratories.

Imidazolium-based ionic liquid surfactants as pseudostationary in combination with a chiral selector in micellar electrokinetic chromatography.

In recent years, ionic liquid-based surfactants have drawn more and more attention. As a new promising brand of surfactants, ionic liquid-based surfactants have their unique properties and superior aggregation behavior, which can be introduced as micellar pseudostationary in MEKC mode. In this paper, a novel ionic liquid-based surfactant, 1-butyl-3-methylimidazolum dodecyl sulfate [C4MIm][C12SO4], was synthesized through ion exchange reaction and applied for the first time to form micellar as pseudostationary phase for chiral separation with clindamycin phosphate as chiral selector. As observed, compared with conventional non-ionic liquid anionic surfactant, improved separation of tested drug enantiomers was obtained in the established MEKC system with ionic liquid-based surfactant. Parameters such as concentration of ionic liquid-based surfactants, type and proportion of organic modifier, concentration of chiral selector, and pH of buffer solution were systematically investigated to optimize the ionic liquid-based surfactant MEKC system. Graphical abstract.

Synthesis and application of amino alcohol-derived chiral ionic liquids, as additives for enantioseparation in capillary electrophoresis

In this study, three functionalized chiral ionic liquids (CILs) derived from l-valinol, l-prolinol and l-phenylalaninol, namely N,N,N-trimethyl-l-valinol-bis(trifluoromethanesulfon)imide ([TMLV]+[Tf2N]−, CIL1), N,N-dimethyl-l-prolinol-bis(trifluoromethanesulfon)imide ([DMLP]+[Tf2N]−, CIL2) and N,N,N-trimethyl-l-phenylalaninol-bis(trifluoromethanesulfon)imide ([TMLP]+[Tf2N]−, CIL3), were synthesized and subsequently utilized for enantiomeric separation in capillary electrophoresis (CE) with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) as chiral selector for the first time. Compared with traditional single HP-β-CD separation system, the synergistic system exhibited substantially improved separations of six tested drugs. Using the CIL1/HP-β-CD as a model system, the influence of crucial parameters including the type and proportion of organic modifier, CILs concentration, HP-β-CD concentration and buffer pH was investigated in detail. Additionally, molecular modeling with AutoDock was applied to elucidate the enhanced enantioselectivity in the presence of CILs, which has certain guiding value in predicting the migration order of the enantiomers and studying the interactions important for the chiral recognition.

Determination of daptomycin in human plasma and breast milk by UPLC/MS-MS

During the lactation, the choice of a proper antibiotic is crucial since the drug can cross into breast milk causing toxicity to the infant. Therefore, an extraction protocol and LC/MS-MS method for the determination of daptomycin in human milk and plasma were developed, validated and applied to a case of a breastfeeding mother affected by a purulent acute soft skin infection treated with daptomycin. Because of daptomycin high protein binding and its high molecular weight, the optimisation of the extraction protocol and analytical conditions were deeply investigated, and several parameters were taken into account: in particular the type of extraction, internal standard, the type of organic modifier, pH of the aqueous solution, and gradient. The use of a protein precipitation protocol coupled to a C8-reverse phase LC-MS/MS allows for a reliable quantification of daptomycin in both plasma (in the range of 19–199 μg/mL) and breast milk (in the range of 0.12–0.32 μg/mL). The determination of milk/plasma (M/P) ratio, which ranged from 0.002 to 0.006, allowed to assess that daptomycin, effective for the mother, was contemporarily safe for the breastfed newborn.

Investigation of the enantioselectivity of tetramethylammonium-lactobionate chiral ionic liquid based dual selector systems toward basic drugs in capillary electrophoresis.

Recently, chiral ionic liquids (CILs) have received increasing interest in chiral separation by CE. Nevertheless, the lack of deep perception of the specific mechanism about CILs in CE for enantioseparation still perplexes a legion of researchers, despite the strenuous efforts. In this paper, a lactobionic acid based ionic liquid, tetramethylammonium-lactobionate (TMA-LA) was applied for the first time in CE to establish dual selector system with clindamycin phosphate (CP) for enantiomeric separation. Compared to single CP system or single TMA-LA system significantly improved separations of seven tested rameric drugs (propranolol, nefopam, citalopram, chlorphenamine, metoprolol, bisoprolol, and esmolol) were observed in the dual selector systems. Several crucial parameters such as type and proportion of organic modifier, buffer composition and pH, and concentration of TMA-LA/CP were systematically investigated to achieve satisfied enantioseparation. Meanwhile, molecular modeling was applied to demonstrate the chiral recognition mechanism of the TMA-LA/CP dual-selector separation system using the molecular docking software Autodock, which well supported the experimental results. The existence of TMA-LA/CP complex may give rise to a higher discriminatory ability against the enantiomers, indicating the reason of improved separation in TMA-LA/CP system. All the influence factors evaluated by means of Statistical Product and Service Solutions (SPSS) to research the influences on the chiral separation system.

Enantioseparation of tryptophan and its unnatural derivatives by nano-LC on CSP-teicoplanin silica based.

This work deals with the potentiality of nano liquid chromatography (Nano-LC) for the chiral separation of racemic mixture of tryptophan and some selected derivatives by using 100µm i.d. fused silica capillary packed with teicoplanin bonded to 5µm diol silica stationary phase. The experiments were carried out by using a cheap and laboratory-assembled nano-LC-UV system. Elution was done in an isocratic mode using a polar organic mobile phase. In order to find the optimum chiral separation of the studied enantiomers, some chromatographic experimental parameters were systematically studied and optimized. Among them, mobile phase composition, namely organic modifier type and concentration, buffer type and pHand aqueous content and sample solvent dilution on retention time, retention factor and enantioresolution factor were studied. Baseline enantioresolution and good peak shape was achieved utilizing the mobile phase containing 40mM ammonium formate at pHpH2.5 in ACN/water/acetone (60:30:10, v/v/v) at 520nL/min in less than 8min analysis time.

Synthesis and application of amino triazolium-modified lactobionic acid as chiral selector in capillary electrophoresis

In this paper, a chiral selector, N-(4-H-1, 2, 4-triazolium)-lactobionamides (LA-ATM), was synthesized and applied for enantioseparation in capillary electrophoresis (CE) for the first time. Compared with lactobionic acid (LA) separation system, enhanced enantioseparation of five tested drugs was achieved in this modification system. In order to achieve good chiral separation, several parameters such as chiral selector concentration, buffer pH, applied voltage as well as the type and proportion of organic modifier were systematically investigated. Molecular modeling was applied to demonstrate the chiral recognition mechanism of the LA-ATM, which well supported the experimental results. Furthermore, a mathematical equation built up based on the molecular mechanics calculations was used in predicting resolution of tested drugs using LA or LA-ATM mediated CE, the predicted result was well correlated with the experimental result.

Polymeric stationary phases based on poly(butylene terephthalate) and poly(4-vinylpirydine) in the analysis of polyphenols using supercritical fluid chromatography. Application to bee pollen

Two new polymer-based stationary phases; DCpak PBT (poly(butylene terephthalate)) and DCpak P4VP (poly(4-vinylpirydine)) were evaluated for the analysis of polyphenols using supercritical fluid chromatography (SFC). The compounds studied included phenolic acids and flavonoids. The different variables that influence the chromatographic separation, such as type and percentage of organic modifier, additive, pressure and temperature were examined. Using the DCpak P4VP column the retention was exceptionally high, obtaining better results with the DCpak PBT column. The separation of nine polyphenols was achieved using a gradient of modifier (methanol with 0.1% trifluoroacetic acid) from 5 to 50%, a pressure of 150 bar, a temperature of 35 °C and a flow-rate of 2 mL/min. The use of additives was necessary in order to obtain good peak shapes and efficiencies, achieving the best results with trifluoroacetic acid. LODs and LOQs values were lower than 5 μg/mL in all the cases; meanwhile, the %RSD values for method repeatability and inter-day reproducibility were lower than 3% and 10% respectively. Finally, the proposed method was successfully applied to the analysis of polyphenols in commercial bee pollen; four compounds, namely cinnamic acid, p-coumaric acid, catechin and quercetin were identified and quantified.

The influence of addition of ion-pairing acid and organic modifier of the mobile phase on retention and migration of peptides in pressurized planar electrochromatography system with octadecyl silica-based adsorbent

In our previous papers we have investigated the influence of the mobile phase composition on mechanism of retention, selectivity and efficiency of peptide separation in various high-performance thin-layer chromatography (HPTLC) systems with commercially available silica-based adsorbents. We have also investigated the influence of pH of the mobile phase buffer on migration and separation of peptides in pressurized planar electrochromatography (PPEC). Here we investigate the influence of concentration of ion-pairing additive, and concentration and type of organic modifier of the mobile phase on migration of peptides in PPEC system with octadecyl silica-based adsorbent, and with the same set of the solutes as before. We compare our current results with the results obtained before for similar HPTLC and PPEC systems, and discuss the influence of particular variables on retention, electrophoretic mobility of solutes and electroosmotic flow of the mobile phase. We show, that the final selectivity of peptide separation results from co-influence of all the three factors mentioned. Concentration of organic modifier of the mobile phase, as well as concentration of ion-pairing additive, affect the retention, the electrophoretic mobility, and the electroosmotic flow simultaneously. This makes independent optimization of these factors rather difficult. Anyway PPEC offers much faster separation of peptides with quite different selectivity, in comparison to HPTLC, with similar adsorbents and similar mobile phase composition. However, we also present and discuss the issue of extensive tailing of peptide zones in the PPEC in comparison to similar HPTLC systems.

Solid-Surface Modification with Two-Dimensionally Ordered Oriented Molecular Films

The surface properties of solid substrates have a considerable impact on many physical, chemical, and electrochemical events occurring at a materials interface, and thus the control of chemical and physical properties of solid surfaces (e.g., surface morphology and energy, wettability, and adhesiveness) provides a key technology in many practical applications. As a useful approach for this purpose, the formation of self-assembled monolayers (SAMs) has widely been used, which relies on specific bonding between polar functional groups of organic molecules and outermost surface elements of inorganic substrates. However, this approach cannot be applied for the modification of polymer substrate surfaces, which are devoid of any effective binding site against polar functional groups. Here we report a new type of organic surface modifier consisting of a paraffinic tripodal triptycene, which undergoes controlled self-assembly not only on inorganic substrates but also on polymer substrates, resulting in a completely oriented molecular thin film like SAMs. The formation of this molecular film does not rely on specific chemical bonding but on a unique assembling property of the molecular building block capable of forming 2D (hexagonal triptycene array) + 1D (layer stacking) structure regardless of the types of substrates. In this presentation, an application of this molecular film to organic electronic devices, which can enhance device performances, will also be described.

Analysis of oligonucleotides by ion-pairing hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry.

Hydrophilic interaction liquid chromatography/electrospray ionization mass spectrometry (HILIC-LC/ESI-MS) has been proved to be useful for the quality control of oligonucleotides. However, the lack of separation for some oligonucleotides using HILIC-LC/MS has proved problematic. This study aimed to improve the resolving ability of HILIC-LC/MS. The study was performed on a Waters UPLC® system coupled to a Waters LCT premier XE ESI-TOF mass spectrometer using a Zorbax® RRHD HILIC column (2.1mm×100mm, 1.8μm). Buffer systems contained triethylammonium acetate (TEAA) and acetonitrile. The effects of the concentration of TEAA and the type of organic modifiers on the separation of oligonucleotides were investigated. The results showed that the optimum concentration of TEAA is 10mM and acetonitrile is a better organic solvent than methanol. The addition of TEAA in the HILIC mobile phase improved the separation of N from N+A significantly compared to the HILIC method buffered with ammonium acetate. The IP-HILIC chromatography has demonstrated that the separation of oligonucleotides is sequence dependent. In addition, the IP-HILIC method produces a much simpler mass spectrum of an oligonucleotide with very efficient desalting. The HILIC-LC/MS method with the addition of TEAA at a MS-compatible concentration has improved the separation of oligonucleotides. The IP-HILIC-LC/MS method also produces very simple mass spectra with high desalting efficiency.

The cation-selective exhaustive injection and sweeping capillary electrophoresis method for the analysis of chlorpheniramine enantiomers in rat plasma

Chlorpheniramine is a potent antihistaminic administered as a racemic mixture, while its clinical activity is mainly associated with the S-enantiomer. In this study, a sensitive and rapid on-line preconcentration capillary electrophoresis (CE) method, cation-selective exhaustive injection (CSEI) and sweeping method was established and validated for the analysis of two chlorpheniramine enantiomers. Parameters influencing separation and enhancement efficiency were investigated, including cyclodextrin (CD) types and concentration, background electrolyte pH, type and content of organic modifier, injection time of water plug, injection time and voltage of sample. A zone of 30mM Tris buffer at pH 3.5 without chiral selector was injected into the capillary followed by a 3s water plug, allowing for the analytes to be electrokinetically injected at a voltage of 10kV for 80s. A 30mM Tris buffer at pH 3.5 consisting of 20mM sulfated-β-cyclodextrin (S-β-CD) and 5% methanol was found to be highly efficient for the separation of the two enantiomers. The present method manifested that high sensitivity (0.025μg/mL for the thethe lower limit of quantification), satisfactory accuracy (89.2%–95.0%) and precision (relative standard deviation within 8.4%) were achieved as well as favourable stability. The extraction recoveries of two enantiomers were both above 72.5%. Finally, the developed method was successfully applied to pharmacokinetic study of the two enantiomers in rat plasma after oral administration of racemic chlorpheniramine.

Lipophilicity estimation of statins as a decisive physicochemical parameter for their hepato-selectivity using reversed-phase thin layer chromatography

Lipophilicity plays a crucial role in determining the hepato-selectivity and hence, the biological activity and the associated side effects of statins. Herein, the employment of RP-TLC for estimation of lipophilicity of six statins namely; atorvastatin, simvastatin, pravastatin, lovastatin, rosuvastatin and fluvastatin is examined. A very good correlation between the chromatographically-determined retention parameters (relative lipophilicity (RM0) or lipophilic parameter (C0)) and both experimental and computed log P values were obtained. However, the results indicate that the type of organic modifier in the mobile phase system (methanol, acetonitrile and acetone) has a small influence on RM0 or C0 values. Higher values of RM0 or C0 are ascribed to lipophilic statins and lower values of RM0 or C0 are attributed to hydrophilic ones. Therefore, RM0 or C0 could be effectively used as simple practical predictors of extra-hepatic distributions of statins and thus their expected side effects. Furthermore, three QSPR (quantitative structure-property relationship) models were constructed to describe the relationship between RM0 with log P and log D of the statins under investigation. These models can be very useful to predict the lipophilicity of other members of statin drugs and might be expanded to newly synthesized compounds with the same structural features.

Affinity capillary electrophoresis and fluorescence spectroscopy for studying enantioselective interactions between omeprazole enantiomer and human serum albumin.

Baseline separation of omeprazole (OME) enantiomers was achieved by affinity capillary electrophoresis (ACE), using human serum albumin (HSA) as the chiral selector. The influence of several experimental variables such as HSA concentration, the type and content of organic modifiers, applied voltage and running buffer concentration on the separation was evaluated. The binding of esomeprazole (S-omeprazole, S-OME) and its R-enantiomer (R-omeprazole, R-OME) to HSA under simulated physiological conditions was studied by ACE and fluorescence spectroscopy which was considered as a reference method. ACE studies demonstrated that the binding constants of the two enantiomers and HSA were 3.18 × 103 M-1 and 5.36 × 103 M-1 , respectively. The binding properties including the fluorescence quenching mechanisms, binding constants, binding sites and the number of binding sites were obtained by fluorescence spectroscopy. Though the ACE method could not get enough data when compared with the fluorescence spectrum method, the separation and binding studies of chiral drugs could be achieved simultaneously via this method. This study is of great significance for the investigation and clinical application of chiral drugs.

Vermiculite/poly(lactic acid) composites: Effect of nature of vermiculite on hydrolytic degradation in alkaline medium

Unmodified and different organomodified vermiculites were used for the preparation of poly(l-lactide) (PLLA) composites via melt mixing. The effect of the clay mineral surface modification, the type of organic modifier of the vermiculite and sample thickness on the degradation of PLLA in alkaline medium at 37°C was studied. The degradation was evaluated by analyzing mass loss, pH, molecular weights, and morphological changes. Alkaline hydrolysis of PLLA was accelerated by the presence of clay mineral and the degradation rate was very much dependent on type of clay mineral and state of dispersion. Morphological changes suggested that the erosion mechanism of polymer matrix occurred at the film surfaces and started at the interface of polymer and clay minerals. The results presented here show that the hydrolytic degradation of PLLA can be controlled through the preparation of nanocomposites introducing the appropriate organomodified nanoclay mineral.

Enantioseparation of drugs by capillary electrochromatography using a stationary phase covalently modified with graphene oxide

The authors describe the fabrication of a stationary phase for use in enantioseparation in capillary electrochromatography (CEC). The stationary phase was obtained by covalent immobilization of graphene oxide (GO) on the inner walls of a fused-silica capillary. Methyl-β-cyclodextrin was used as the chiral selector, and the enantiomers were detected by UV absorptiometry. Compared with uncoated fused-silica capillary, obviously improved separation of three tested drug enantiomers was obtained in the GO-polymer coated capillary column (the resolution of Naproxen: 0 → 1.56, Warfarin: 0 → 1.89 and Pranoprofen:0 → 1.51). The effects of buffer pH, type and proportion of organic modifier, concentration of chiral selector and applied voltage were optimized. Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results.

Stereoselective quantification of triticonazole in vegetables by supercritical fluid chromatography

A highly fast analytical method though supercritical fluid chromatography (SFC) has been developed to quantify triticonazole enantiomers in cucumbers and tomatoes. Effects of organic modifier type and concentration on chiral separation and quantification of standard solution as well as matrix-matched standard solutions have been studied in detail. Among three organic modifiers, better separation of triticonazole racemate was achieved with 20% ethanol (v/v). The run time in SFC (ca 3min) with CO2-ethanol (80:20, v/v) as the mobile phase was six-fold shorter than HPLC analysis (about 18min). Then, QuEChERS (quick, easy, cheap, effective, rugged and safe) extraction procedure was used for triticonazole in vegetables. The residue analysis method was validated. Good linearity (R2≥0.9988) and recoveries (81.62–106.21%, RSD≤7.30%) for the two enantiomers were achieved. This developed method described herein is convenient and reliable for enantioselective detection of triticonazole in vegetables, which might provide additional information for reliable risk assessment of chiral pesticides.