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ABSTRACT The increased production of drugs requires a concomitant assessment of drug purity. Chromatography in general, and thin layer chromatography in particular, play an important role in determination of the impurity profiles of drug... more
ABSTRACT The increased production of drugs requires a concomitant assessment of drug purity. Chromatography in general, and thin layer chromatography in particular, play an important role in determination of the impurity profiles of drug candidates. However, in using chromatography to determine impurities, the chemist must be careful, since extraneous zones or spots do not always indicate impurities. They may instead be artifacts, produced in the chromatographic system. In this paper we present a phenomenon related to on-plate decomposition. MK0912 was chosen as a model compound. To overcome the on-plate degradation an inclusion compound was formed with γ-cyclodextrin in the spotting solution, followed by a mobile phase containing hexadecyltrimethylammonium bromide as a micelle generator. This technique proved to be successful for preventing degradation during chromatography.
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This work investigates the origins of enantioselectivity of polymers imprinted with the HIV protease inhibitor, Indinavir. For the preparation of imprints of the drug, the critical interactions between the functional monomer, methacrylic... more
This work investigates the origins of enantioselectivity of polymers imprinted with the HIV protease inhibitor, Indinavir. For the preparation of imprints of the drug, the critical interactions between the functional monomer, methacrylic acid, and Indinavir were characterized by infrared (IR) spectroscopy to explore the optimum functional monomer concentration for the polymerization. It was shown that a polymer with high selectivity and minimum non-selective binding for Indinavir was obtained when prepared with enough functional monomer to hydrogen bond with all of the functional groups of the drug without using an excess of monomer. This observation is explained in terms of a balance that is achieved in the monomer-template equilibrium during the polymerization that yields a polymer with highly selective sites and minimal non-selective sites. This paper further demonstrates that IR spectroscopy can be a valuable tool in the design and syntheses of molecular imprinted polymers.
Research Interests: Chemistry, Molecular Imprinting, Polymers, Medicine, Polymerization, and 15 morePolymer, Infrared spectroscopy, High Performance Liquid Chromatography, Hydrogen Bond, Infrared, Monomer, IR Spectroscopy, Functional Group, A, Methacrylic Acid, Molecular Structure, Enantiomer, Selectivity, indinavir, and Methacrylates
Separation of enantiomers has become a well-established technique in many fields of science over the last decade. Unfortunately, even though there are a large number of chiral stationary phases able to perform enantiomeric separation,... more
Separation of enantiomers has become a well-established technique in many fields of science over the last decade. Unfortunately, even though there are a large number of chiral stationary phases able to perform enantiomeric separation, there is still a great deal of trial and error in developing a method for the separation of enantiomers. Thin-layer chromatography is a very versatile technique, which has brought much advancement in various fields of science. The simplicity of the technique makes it amenable for separation of enantiomers. This paper will present a review of the literature concerning separation of enantiomers. Because of the process of trial and error present in developing a chiral separation method, this paper also presents the mechanism underlying each form of separation. Thus, the methods are presented according to the main mechanism governing the particular separation.
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Research Interests:
This article describes the direct separation of an HIV-1 reverse transcriptase inhibitor and its enantiomer by HPLC on a silica-bonded polyacrylamide (ChiraSpher) column. The column selection was based on specific interactions between the... more
This article describes the direct separation of an HIV-1 reverse transcriptase inhibitor and its enantiomer by HPLC on a silica-bonded polyacrylamide (ChiraSpher) column. The column selection was based on specific interactions between the individual enantiomers and the chiral stationary phase. The influence of some Chromatographic conditions, such as concentration of the polar modifier in the mobile phase, column flow-rate and column temperature, on column performance was investigated. The separation was applied to the determination of the minor enantiomer in the bulk drug and as low as 0.3% of minor enantiomer was detectable.
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Research Interests:
Research Interests:
Thin Layer Chromatography (TLC) is an established method for the evaluation of final product drug and intermediate impurity profiles. Quantitative TLC has gained credibility within the Pharmaceutical industry as a result of the latest... more
Thin Layer Chromatography (TLC) is an established method for the evaluation of final product drug and intermediate impurity profiles. Quantitative TLC has gained credibility within the Pharmaceutical industry as a result of the latest developments in an availability of scanning technology. In the present paper we wish to report a quantitative TLC method for the determination of some potential impurities
Research Interests:
Research Interests:
A method for analysis of residual azide in an organic matrix (triazole derivative) is described. The azide was separated from the matrix using a solid phase extraction cartridge, and analyzed using reversed-phase chromatography with... more
A method for analysis of residual azide in an organic matrix (triazole derivative) is described. The azide was separated from the matrix using a solid phase extraction cartridge, and analyzed using reversed-phase chromatography with direct UV detection. The analysis of azide was used as a limit test for a level of 20 ppm relative to the weight of the organic matrix. Thermodynamic studies of the chromatographic system suggested that the interaction between azide and the stationary phase was hydrophobic in nature.
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Research Interests: Engineering, Chemistry, Technology, Chromatography, Kinetics, and 13 moreMagnetic Resonance Spectroscopy, Medicine, Temperature, Activation Energy, High Performance Liquid Chromatography, High Pressure Liquid Chromatography, CHEMICAL SCIENCES, Derivatization, Aldehyde, Reaction Rate, Gradient Method, Aldehydes, and kinetic analysis
LCMS incorporating a quadrupole time of flight mass spectrometer was used to identify impurities found in a chemical process development sample of a novel integrase inhibitor, raltegravir. The combination of accurate mass measurement in... more
LCMS incorporating a quadrupole time of flight mass spectrometer was used to identify impurities found in a chemical process development sample of a novel integrase inhibitor, raltegravir. The combination of accurate mass measurement in full scan mode followed by construction of targeted masses for further MSMS interrogation allowed for the determination of atomic composition and connectivity. The fragmentation pattern of raltegravir was used as a model compound, and the product ion spectra of an impurity was compared to both the model fragmentation pattern and the atomic composition generated in the full scan experiment to deduce a structure.
Research Interests: Chemistry, Analytical Chemistry, Mass Spectrometry, Pharmaceutical Chemistry, Medicine, and 8 moreTime of Flight, Impurity, Quadrupole, High Pressure Liquid Chromatography, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Hiv Integrase Inhibitors, Process Development, and Pharmacology and pharmaceutical sciences
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Research Interests:
Abstract The incorporation of a complexing agent within a polyarcylamide gel column provides a general means of manipulating the selectivity of a capillary electrophoresis separation. As an example of this approach, chiral resolution of... more
Abstract The incorporation of a complexing agent within a polyarcylamide gel column provides a general means of manipulating the selectivity of a capillary electrophoresis separation. As an example of this approach, chiral resolution of dansylated amino acids ...
Research Interests:
Research Interests:
Research Interests:
Research Interests: Chemistry and Enantiomer
Thin Layer Chromatography (TLC) is an established method for the evaluation of final product drug and intermediate impurity profiles. Quantitative TLC has gained credibility within the Pharmaceutical industry as a result of the latest... more
Thin Layer Chromatography (TLC) is an established method for the evaluation of final product drug and intermediate impurity profiles. Quantitative TLC has gained credibility within the Pharmaceutical industry as a result of the latest developments in an availability of scanning technology. In the present paper we wish to report a quantitative TLC method for the determination of some potential impurities
Research Interests:
ABSTRACT The increased production of drugs requires a concomitant assessment of drug purity. Chromatography in general, and thin layer chromatography in particular, play an important role in determination of the impurity profiles of drug... more
ABSTRACT The increased production of drugs requires a concomitant assessment of drug purity. Chromatography in general, and thin layer chromatography in particular, play an important role in determination of the impurity profiles of drug candidates. However, in using chromatography to determine impurities, the chemist must be careful, since extraneous zones or spots do not always indicate impurities. They may instead be artifacts, produced in the chromatographic system. In this paper we present a phenomenon related to on-plate decomposition. MK0912 was chosen as a model compound. To overcome the on-plate degradation an inclusion compound was formed with γ-cyclodextrin in the spotting solution, followed by a mobile phase containing hexadecyltrimethylammonium bromide as a micelle generator. This technique proved to be successful for preventing degradation during chromatography.
Research Interests:
ABSTRACT Method validation is an important step in any method development and has important implications in the pharmaceutical industry. Particular efforts should be directed towards the reproducibility, sensitivity and ruggedness of each... more
ABSTRACT Method validation is an important step in any method development and has important implications in the pharmaceutical industry. Particular efforts should be directed towards the reproducibility, sensitivity and ruggedness of each method developed. In this paper, we report the validation of an HPLC method for the separation of the L-699, 392 and its (S, R) diastereomer. This compound contains two chiral centers and a carboxyl functionality able to participate in a hydrogen bonding process. In order to obtain maximum sensitivity, the elution order of the two diastereomers was adjusted such that the minor diastereomer eluted before the major one. To achieve this elution order a nonpolar mobile phase consisting of methylene chloride and n-propanol containing quinine as a hydrogen bond acceptor was used. In order to optimize the separation, the influence of quinine concentration on the capacity and separation factor of the two diastereomers, influence of the polar modifier in the mobile phase and influence of the flow rate on the separation factor and system efficiency, were studied.The method has been shown to be rugged giving base line separation of the two diastereomers with a limit of detection of 0.06% by weight for the minor diastereomer (S, R). The detector response of the (S, S) diastereomer was linear in the range 0.0005 to 1.1 mg/ml with an r of 0.9996. The injection precision, linearity of the detector response and solution stability were also evaluated.
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Separation of enantiomers has become a well-established technique in many fields of science over the last decade. Unfortunately, even though there are a large number of chiral stationary phases able to perform enantiomeric separation,... more
Separation of enantiomers has become a well-established technique in many fields of science over the last decade. Unfortunately, even though there are a large number of chiral stationary phases able to perform enantiomeric separation, there is still a great deal of trial and error in developing a method for the separation of enantiomers. Thin-layer chromatography is a very versatile technique, which has brought much advancement in various fields of science. The simplicity of the technique makes it amenable for separation of enantiomers. This paper will present a review of the literature concerning separation of enantiomers. Because of the process of trial and error present in developing a chiral separation method, this paper also presents the mechanism underlying each form of separation. Thus, the methods are presented according to the main mechanism governing the particular separation.
Research Interests:
Research Interests:
LCMS incorporating a quadrupole time of flight mass spectrometer was used to identify impurities found in a chemical process development sample of a novel integrase inhibitor, raltegravir. The combination of accurate mass measurement in... more
LCMS incorporating a quadrupole time of flight mass spectrometer was used to identify impurities found in a chemical process development sample of a novel integrase inhibitor, raltegravir. The combination of accurate mass measurement in full scan mode followed by construction of targeted masses for further MSMS interrogation allowed for the determination of atomic composition and connectivity. The fragmentation pattern of raltegravir was used as a model compound, and the product ion spectra of an impurity was compared to both the model fragmentation pattern and the atomic composition generated in the full scan experiment to deduce a structure.
Research Interests: Chemistry, Analytical Chemistry, Mass Spectrometry, Pharmaceutical Chemistry, Medicine, and 8 moreTime of Flight, Impurity, Quadrupole, High Performance Liquid Chromatography, Liquid Chromatography / Electrospray Ionization Mass Spectrometry, Hiv Integrase Inhibitors, Process Development, and Pharmacology and pharmaceutical sciences
Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of... more
Effective process control can only be achieved through an understanding of the operating issues of the reaction. The development and use of effective and rugged analytical methods is necessary to monitor these parameters. The intent of this paper is to present some key analytical issues encountered in the synthesis of MK-0679, an LTD4 antagonist. In a key step of the
Research Interests: Chemistry, Analytical Chemistry, Chromatography, Process Control, Medicine, and 9 moreFlow Injection Analysis, Combinatorial Chemistry, High Performance Liquid Chromatography, Analytical Method, Enzyme activity, Enzymatic Activity, Hydrolysis, Enzymatic hydrolysis, and Pharmacology and pharmaceutical sciences
A method for analysis of residual azide in an organic matrix (triazole derivative) is described. The azide was separated from the matrix using a solid phase extraction cartridge, and analyzed using reversed-phase chromatography with... more
A method for analysis of residual azide in an organic matrix (triazole derivative) is described. The azide was separated from the matrix using a solid phase extraction cartridge, and analyzed using reversed-phase chromatography with direct UV detection. The analysis of azide was used as a limit test for a level of 20 ppm relative to the weight of the organic matrix. Thermodynamic studies of the chromatographic system suggested that the interaction between azide and the stationary phase was hydrophobic in nature.
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... DOI: 10.1081/JLC-120017180 S. Chen a * , H. Yuan a , N. Grinberg a , A. Dovletoglou a & G. Bicker a pages 425-442. Available online: 24 ... 22]22. Shinbo, T., Yamaguchi, T., Nishimura, K. and Suguira, M. 1987. J.... more
... DOI: 10.1081/JLC-120017180 S. Chen a * , H. Yuan a , N. Grinberg a , A. Dovletoglou a & G. Bicker a pages 425-442. Available online: 24 ... 22]22. Shinbo, T., Yamaguchi, T., Nishimura, K. and Suguira, M. 1987. J. Chromatogr. , 405 ...
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Research Interests:
Research Interests: Engineering, Chemistry, Technology, Chromatography, Kinetics, and 13 moreMagnetic Resonance Spectroscopy, Medicine, Temperature, Activation Energy, High Performance Liquid Chromatography, High Pressure Liquid Chromatography, CHEMICAL SCIENCES, Derivatization, Aldehyde, Reaction Rate, Gradient Method, Aldehydes, and kinetic analysis
This paper explores the role of association on the adsorption isotherms of beta-lactoglobulin A on a weakly hydrophobic stationary phase at 4 degrees C and mobile phases of 0.85 M and 1 M ammonium sulfate, pH 4.5. The isotherms, obtained... more
This paper explores the role of association on the adsorption isotherms of beta-lactoglobulin A on a weakly hydrophobic stationary phase at 4 degrees C and mobile phases of 0.85 M and 1 M ammonium sulfate, pH 4.5. The isotherms, obtained by frontal analysis, show an S-shape and the corresponding Scatchard plots indicate positive cooperativity. The slopes and intercepts of the Scatchard plots at low solute concentration are analyzed in terms of two species--a promoter and a higher order stronger adsorbing species. An explicit equation of the isotherm is developed based on this model, and this expression is shown to reproduce the isotherm shape using the appropriate derived parameters. It is further shown from this equation that a Langmuir-shaped adsorption isotherm can be obtained if the higher order associate or aggregate binds weaker to the support than the promoter. These results indicate that protein-protein interactions and the formation of associates can play a significant role on the shape of the isotherm and ultimately on the behavior of the species in preparative scale chromatography.
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Research Interests:
Abstract The incorporation of a complexing agent within a polyarcylamide gel column provides a general means of manipulating the selectivity of a capillary electrophoresis separation. As an example of this approach, chiral resolution of... more
Abstract The incorporation of a complexing agent within a polyarcylamide gel column provides a general means of manipulating the selectivity of a capillary electrophoresis separation. As an example of this approach, chiral resolution of dansylated amino acids ...
Research Interests:
Research Interests:
ABSTRACT An ion chromatographic method for the determination of the residual acetate in hulk drug was developed. The drug was MK0476, an LTD4 antagonist. The compound also has a carboxyl functionality, which would interfere with the... more
ABSTRACT An ion chromatographic method for the determination of the residual acetate in hulk drug was developed. The drug was MK0476, an LTD4 antagonist. The compound also has a carboxyl functionality, which would interfere with the detection of the acetate ion. A solid phase extraction through a Sep-Pak cartridge was pursued for the removal of MK0476 from the matrix. Since the analyte does not have a chromophore, a mobile phase containing trimesic acid facilitated its detection by indirect photometric detection. The separation was performed on a polymeric strong union exchange column. The influence of pH, concentration of trimesic acid, and temperature were studied. Chloride ion was found to be a contaminant that was interfering in the analysis. To improve the separation between chloride and acetate ions, methanol was added to the mobile phase, leading to complete separation between the two species. Recovery of the acetate ion was determined as 92.3%. The method was applied to real samples with good results. It was shown to be sensitive for the determination of less than 0.001 mg/ml of acetate with a linear range of 0.00036 to 0.074 mg/ml.
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Research Interests:
Research Interests:
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Phosphine boranes have been found to hydrophosphinate internal, unactivated alkynes at room temperature under basic conditions without the need for catalysts or radical initiators. The use of air-sensitive secondary phosphines is avoided... more
Phosphine boranes have been found to hydrophosphinate internal, unactivated alkynes at room temperature under basic conditions without the need for catalysts or radical initiators. The use of air-sensitive secondary phosphines is avoided in this facile process. Broad scope in both the phosphine borane and alkyne partners leads to excellent diversity in the phosphine products. Asymmetric hydrogenation of these species then provides one of the shortest possible routes to chiral monodentate phosphines. Hydrophosphination of allenyl phosphine oxides under similar conditions followed by hydrogenation of the exomethylene moiety yields a wide variety of bis-phosphine derivatives.
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Research Interests: Catalysis, Hydrogenation, Urea, Organic, CHEMICAL SCIENCES, and 4 moreRhodium, Esters, Ligands, and Molecular Structure
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An enantioselective hydrogenation of hydrazones derived from heterocyclic ketones was developed with up to 85% ee. The enantiomeric purity was enriched to >99% ee by crystallization from EtOAc in >80% yield. Optimization studies have... more
An enantioselective hydrogenation of hydrazones derived from heterocyclic ketones was developed with up to 85% ee. The enantiomeric purity was enriched to >99% ee by crystallization from EtOAc in >80% yield. Optimization studies have revealed a notable solvent effect that resulted in inversion of enantioselectivity from 85% ee in MeOH to −27% ee in DCE. The hydrazone geometry and possible hydrogenation via endocyclic alkene were examined as possible factors for the inversion of enantioselectivity.
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Abstract: Three different protocols to synthesize oxazolidin-5-ones have been studied with the goal to develop a method to synthesize a diastereomerically pure oxazolidin-5-one. A novel method is reported that uses a dynamic... more
Abstract: Three different protocols to synthesize oxazolidin-5-ones have been studied with the goal to develop a method to synthesize a diastereomerically pure oxazolidin-5-one. A novel method is reported that uses a dynamic crystallization-induced asymmetric ...