Thomas Feinberg - Academia.edu (original) (raw)
Papers by Thomas Feinberg
Applied Spectroscopy Reviews, Aug 1, 1995
Environmental science strives to understand the formation, disposition, transport, and transforma... more Environmental science strives to understand the formation, disposition, transport, and transformation of pollutants in the environment. Explorations of reaction chemical kinetics and mechanisms, chemical and biological transformations of anthropogenic contaminants, and the transport of contaminants in atmospheric and aquatic systems represent the nature of research conducted. The performance of this research depends on the development and application of analytical techniques
Safety Evaluation, Qualification, and Best Practices Applied to Inhalation Drug Products, 2012
The Journal of Physical Chemistry, 1992
Safety Evaluation, Qualification, and Best Practices Applied to Inhalation Drug Products, 2012
As detailed in earlier chapters of this volume, organic extractables and leachables can represent... more As detailed in earlier chapters of this volume, organic extractables and leachables can represent a wide variety of chemical types and classes and be present in both container closure system critical component extracts and drug products at widely varying concentrations. These realities suggest that the problems of qualitative and quantitative analysis of extractables/leachables are more akin to environmental trace analysis problems than to the typical pharmaceutical impurity problem, where one has the known structure and synthetic scheme for the drug substance along with well-established analytical thresholds as starting points. In fact, many of the chemical entities that commonly appear as extractables and leachables are also common environmental target analytes, including such compounds as phthalates, phenols, polyaromatic hydrocarbons (PAHs), and N-nitrosamines. Typical organic pharmaceutical impurities can be present in both drug substance 1-3 (e.g., starting materials, by-products, intermediates, degradation products, reagents, ligands, catalysts, residual solvents) and drug product 4 (e.g., degradation products of drug substance or reaction products of drug substance with an excipient and/or the immediate container closure system). Processes for identifi cation/quantitation and control of these typical pharmaceutical impurities are described and referenced in the scientifi c literature 5,6 and various regulatory guidance documents. 1-4 However, it is important to note that the most widely applied regulatory guidance for drug product impurities, International Conference on Harmonisation (ICH) Q3B(R2), 4 specifi cally excludes from 241 CHAPTER 13
Publisher Summary The chapter presents a discussion on hyphenated characterization techniques. Th... more Publisher Summary The chapter presents a discussion on hyphenated characterization techniques. The two most common chromatographic techniques, high-performance liquid chromatography (HPLC) and gas chromatography (GC) can provide both identity measurements by retention time and purity measurements by area (or area under the curve, AUG) when coupled with the two most widely used detectors, ultraviolet (UV) absorbance and flame ionization detection, respectively. Historically, the procedure for the establishment of a chromatographic method's specificity, in addition to the characterization of impurities and degradants has relied on the simple concept (yet complex laboratory procedures) of isolation and recharacterization using orthogonal techniques (commonly referred to as “offline” analysis). The International Conference on Harmonization guidelines have set the acceptable limit for unknown related compounds of an active pharmaceutical ingredient (API) in both drug substance and drug product at no greater than 0.1% levels. The first exposure to spectroscopy for most scientists is ultraviolet/ visible absorbance. Fourier transform infrared spectroscopy (FTIR) provides a useful “fingerprint” of an organic molecule. The newest instrument in the arsenal of the pharmaceutical scientist is the combination of chromatography with nuclear magnetic resonance (NMR) spectroscopy.
The Journal of Chemical Physics, 1994
ABSTRACT The dissociation dynamics of energy selected ethylene dimer ions is investigated by phot... more ABSTRACT The dissociation dynamics of energy selected ethylene dimer ions is investigated by photoelectron photoion coincidence. The derived dissociation rates as a function of the ion internal energy were found to be identical to those previously measured for rotationally cold C4H+8 ions. This demonstrates that the ethylene dimer ions rearrange to the 2‐butene isomers prior to dissociation. The ethylene dimer ions are produced by ionization of neutral ethylene dimer as well as by dissociative ionization of the neutral trimer. The statistical theory analysis of the kinetic energy released in the dissociative photoionization of the ethylene trimers indicates that these ions dissociate to the 2‐butene ion. At the energies investigated, the evaporation of a single monomer unit from the trimer ion removes sufficient energy to prevent further dissociation of the C4H+8 ions. All of the ethylene trimer ion signal was a result of dissociative ionization of higher order clusters. Finally, we show that the ethylene tetramer ion evaporates an ethylene unit as the core polymerizes to a straight chain hexene ion.
The Journal of Chemical Physics, 1994
The infrared photodissociation spectra of Ar dimer ions have been obtained at several wavelengths... more The infrared photodissociation spectra of Ar dimer ions have been obtained at several wavelengths with a line tunable CO2 laser. The dimer ions were produced by high energy electron impact ionization near or at the nozzle orifice of a supersonic expansion. When the electron beam is focused several millimeters from the nozzle, and the laser polarization is parallel to the
Pharmaceutical Research, 2008
The Product Quality Research Institute Leachables and Extractables Working Group includes pharmac... more The Product Quality Research Institute Leachables and Extractables Working Group includes pharmaceutical development scientists representing industry, government, and academia. The Working Group was created and constituted to address scientific and regulatory questions concerning the pharmaceutical development process for Orally Inhaled and Nasal Drug Products (OINDP) related to organic extractables and leachables. This effort has resulted in the creation of a detailed "Recommendation Document", which was submitted to the U.S. FDA for consideration in September 2006. The recommendations include proposed safety and analytical thresholds for leachables and extractables, as well as detailed "best practice" recommendations for various aspects of the OINDP pharmaceutical development process, including: materials selection for OINDP container closure system components, Controlled Extraction Studies, Leachables Studies, and Routine Extractables Testing. The Working Group's processes and the detailed and comprehensive recommendations that resulted from those processes, demonstrate that the Product Quality Research Institute collaborative process can result in consensus science-based and data driven recommendations that could have a positive effect on patient care. It is anticipated that the Working Group's recommendations will also contribute to the new "Quality by Design" pharmaceutical development paradigm. This commentary summarizes the best practice recommendations within the context of an overall pharmaceutical development process.
PDA journal of pharmaceutical science and technology, 2009
N-nitrosamines are chemical entities, some of which are considered to be possible human carcinoge... more N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte ...
ABSTRACT Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliograph... more ABSTRACT Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliographical references (leaves 186-196).
Pharmaceutical technology, 2002
Contract service providers can help manufacturers navigate through the complexity of developing a... more Contract service providers can help manufacturers navigate through the complexity of developing and testing inhalation drug products.
PDA journal of pharmaceutical science and technology, Jan 14, 2016
A simulating leaching (migration) study was performed on a model container-closure system relevan... more A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products (PODP). This container-closure system consisted of a linear-low density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling) and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.5, aqueous buffer at pH 9.5, and 1/1(v/v) IPA/water), a label was affixed to the filled and capped bottles, the filled bottles were placed into the foil overpouch and the filled and pouched units were stored either upright or inverted for up to 6 months at 40°C. After storage, the leaching solutions were tested for leached substances using multiple complementary analytical techniques to address volatile, semi-volatile, and non-volatile organic and inorganic extractables as potential leachables. The leaching data generat...
Pda Journal of Pharmaceutical Science and Technology Pda, 2009
N-nitrosamines are chemical entities, some of which are considered to be possible human carcinoge... more N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.
Http Dx Doi Org 10 1080 05704929508000908, Aug 22, 2006
Pharmaceutical research, Jan 3, 2015
Pharmaceutical Research, 2015
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliographical refe... more Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliographical references (leaves 186-196).
This chapter discusses the combination of high performance liquid chromatography (HPLC) with comp... more This chapter discusses the combination of high performance liquid chromatography (HPLC) with compound specific detection by mass spectrometry (HPLC/MS or LC/MS), and describes the theory and application of modern LC/MS in its most commonly employed configurations. Included are discussions of the most widely applied ionization processes for LC/MS, and the most useful and commonly used mass analyzers. Particular emphasis is given to HPLC method development, and the impact of employing LC/MS on the method development process. Also included, is a discussion of gas-phase ion chemistry and how chromatography parameters can be employed to manipulate gas-phase ion chemistry to enhance LC/MS analysis. Finally, the relatively new combination of liquid chromatography with nuclear magnetic resonance spectroscopy (LC/NMR) is described and discussed. This discussion includes a critical examination of the costs and benefits of LC/NMR relative to conventional “tube” NMR with off-line sample isolati...
Pharmaceutical Technology, 2002
Applied Spectroscopy Reviews, Aug 1, 1995
Environmental science strives to understand the formation, disposition, transport, and transforma... more Environmental science strives to understand the formation, disposition, transport, and transformation of pollutants in the environment. Explorations of reaction chemical kinetics and mechanisms, chemical and biological transformations of anthropogenic contaminants, and the transport of contaminants in atmospheric and aquatic systems represent the nature of research conducted. The performance of this research depends on the development and application of analytical techniques
Safety Evaluation, Qualification, and Best Practices Applied to Inhalation Drug Products, 2012
The Journal of Physical Chemistry, 1992
Safety Evaluation, Qualification, and Best Practices Applied to Inhalation Drug Products, 2012
As detailed in earlier chapters of this volume, organic extractables and leachables can represent... more As detailed in earlier chapters of this volume, organic extractables and leachables can represent a wide variety of chemical types and classes and be present in both container closure system critical component extracts and drug products at widely varying concentrations. These realities suggest that the problems of qualitative and quantitative analysis of extractables/leachables are more akin to environmental trace analysis problems than to the typical pharmaceutical impurity problem, where one has the known structure and synthetic scheme for the drug substance along with well-established analytical thresholds as starting points. In fact, many of the chemical entities that commonly appear as extractables and leachables are also common environmental target analytes, including such compounds as phthalates, phenols, polyaromatic hydrocarbons (PAHs), and N-nitrosamines. Typical organic pharmaceutical impurities can be present in both drug substance 1-3 (e.g., starting materials, by-products, intermediates, degradation products, reagents, ligands, catalysts, residual solvents) and drug product 4 (e.g., degradation products of drug substance or reaction products of drug substance with an excipient and/or the immediate container closure system). Processes for identifi cation/quantitation and control of these typical pharmaceutical impurities are described and referenced in the scientifi c literature 5,6 and various regulatory guidance documents. 1-4 However, it is important to note that the most widely applied regulatory guidance for drug product impurities, International Conference on Harmonisation (ICH) Q3B(R2), 4 specifi cally excludes from 241 CHAPTER 13
Publisher Summary The chapter presents a discussion on hyphenated characterization techniques. Th... more Publisher Summary The chapter presents a discussion on hyphenated characterization techniques. The two most common chromatographic techniques, high-performance liquid chromatography (HPLC) and gas chromatography (GC) can provide both identity measurements by retention time and purity measurements by area (or area under the curve, AUG) when coupled with the two most widely used detectors, ultraviolet (UV) absorbance and flame ionization detection, respectively. Historically, the procedure for the establishment of a chromatographic method's specificity, in addition to the characterization of impurities and degradants has relied on the simple concept (yet complex laboratory procedures) of isolation and recharacterization using orthogonal techniques (commonly referred to as “offline” analysis). The International Conference on Harmonization guidelines have set the acceptable limit for unknown related compounds of an active pharmaceutical ingredient (API) in both drug substance and drug product at no greater than 0.1% levels. The first exposure to spectroscopy for most scientists is ultraviolet/ visible absorbance. Fourier transform infrared spectroscopy (FTIR) provides a useful “fingerprint” of an organic molecule. The newest instrument in the arsenal of the pharmaceutical scientist is the combination of chromatography with nuclear magnetic resonance (NMR) spectroscopy.
The Journal of Chemical Physics, 1994
ABSTRACT The dissociation dynamics of energy selected ethylene dimer ions is investigated by phot... more ABSTRACT The dissociation dynamics of energy selected ethylene dimer ions is investigated by photoelectron photoion coincidence. The derived dissociation rates as a function of the ion internal energy were found to be identical to those previously measured for rotationally cold C4H+8 ions. This demonstrates that the ethylene dimer ions rearrange to the 2‐butene isomers prior to dissociation. The ethylene dimer ions are produced by ionization of neutral ethylene dimer as well as by dissociative ionization of the neutral trimer. The statistical theory analysis of the kinetic energy released in the dissociative photoionization of the ethylene trimers indicates that these ions dissociate to the 2‐butene ion. At the energies investigated, the evaporation of a single monomer unit from the trimer ion removes sufficient energy to prevent further dissociation of the C4H+8 ions. All of the ethylene trimer ion signal was a result of dissociative ionization of higher order clusters. Finally, we show that the ethylene tetramer ion evaporates an ethylene unit as the core polymerizes to a straight chain hexene ion.
The Journal of Chemical Physics, 1994
The infrared photodissociation spectra of Ar dimer ions have been obtained at several wavelengths... more The infrared photodissociation spectra of Ar dimer ions have been obtained at several wavelengths with a line tunable CO2 laser. The dimer ions were produced by high energy electron impact ionization near or at the nozzle orifice of a supersonic expansion. When the electron beam is focused several millimeters from the nozzle, and the laser polarization is parallel to the
Pharmaceutical Research, 2008
The Product Quality Research Institute Leachables and Extractables Working Group includes pharmac... more The Product Quality Research Institute Leachables and Extractables Working Group includes pharmaceutical development scientists representing industry, government, and academia. The Working Group was created and constituted to address scientific and regulatory questions concerning the pharmaceutical development process for Orally Inhaled and Nasal Drug Products (OINDP) related to organic extractables and leachables. This effort has resulted in the creation of a detailed "Recommendation Document", which was submitted to the U.S. FDA for consideration in September 2006. The recommendations include proposed safety and analytical thresholds for leachables and extractables, as well as detailed "best practice" recommendations for various aspects of the OINDP pharmaceutical development process, including: materials selection for OINDP container closure system components, Controlled Extraction Studies, Leachables Studies, and Routine Extractables Testing. The Working Group's processes and the detailed and comprehensive recommendations that resulted from those processes, demonstrate that the Product Quality Research Institute collaborative process can result in consensus science-based and data driven recommendations that could have a positive effect on patient care. It is anticipated that the Working Group's recommendations will also contribute to the new "Quality by Design" pharmaceutical development paradigm. This commentary summarizes the best practice recommendations within the context of an overall pharmaceutical development process.
PDA journal of pharmaceutical science and technology, 2009
N-nitrosamines are chemical entities, some of which are considered to be possible human carcinoge... more N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte ...
ABSTRACT Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliograph... more ABSTRACT Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliographical references (leaves 186-196).
Pharmaceutical technology, 2002
Contract service providers can help manufacturers navigate through the complexity of developing a... more Contract service providers can help manufacturers navigate through the complexity of developing and testing inhalation drug products.
PDA journal of pharmaceutical science and technology, Jan 14, 2016
A simulating leaching (migration) study was performed on a model container-closure system relevan... more A simulating leaching (migration) study was performed on a model container-closure system relevant to parenteral and ophthalmic drug products (PODP). This container-closure system consisted of a linear-low density polyethylene bottle (primary container), a polypropylene cap and an elastomeric cap liner (closure), an adhesive label (labeling) and a foil overpouch (secondary container). The bottles were filled with simulating solvents (aqueous salt/acid mixture at pH 2.5, aqueous buffer at pH 9.5, and 1/1(v/v) IPA/water), a label was affixed to the filled and capped bottles, the filled bottles were placed into the foil overpouch and the filled and pouched units were stored either upright or inverted for up to 6 months at 40°C. After storage, the leaching solutions were tested for leached substances using multiple complementary analytical techniques to address volatile, semi-volatile, and non-volatile organic and inorganic extractables as potential leachables. The leaching data generat...
Pda Journal of Pharmaceutical Science and Technology Pda, 2009
N-nitrosamines are chemical entities, some of which are considered to be possible human carcinoge... more N-nitrosamines are chemical entities, some of which are considered to be possible human carcinogens, which can be found at trace levels in some types of foods, tobacco smoke, certain cosmetics, and certain types of rubber. N-nitrosamines are of regulatory concern as leachables in inhalation drug products, particularly metered dose inhalers, which incorporate rubber seals into their container closure systems. The United States Food and Drug Administration considers N-nitrosamines (along with polycyclic aromatic hydrocarbons and 2-mercaptobenzothiazole) to be "special case" leachables in inhalation drug products, meaning that there are no recognized safety or analytical thresholds and these compounds must therefore be identified and quantitated at the lowest practical level. This report presents the development of a quantitative analytical method for target volatile N-nitrosamines in a metered dose inhaler drug product, Atrovent HFA. The method incorporates a target analyte recovery procedure from the drug product matrix with analysis by gas chromatography/thermal energy analysis detection. The capability of the method was investigated with respect to specificity, linearity/range, accuracy (linearity of recovery), precision (repeatability, intermediate precision), limits of quantitation, standard/sample stability, and system suitability. Sample analyses showed that Atrovent HFA contains no target N-nitrosamines at the trace level of 1 ng/canister.
Http Dx Doi Org 10 1080 05704929508000908, Aug 22, 2006
Pharmaceutical research, Jan 3, 2015
Pharmaceutical Research, 2015
Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliographical refe... more Thesis (Ph. D.)--University of North Carolina at Chapel Hill, 1991. Includes bibliographical references (leaves 186-196).
This chapter discusses the combination of high performance liquid chromatography (HPLC) with comp... more This chapter discusses the combination of high performance liquid chromatography (HPLC) with compound specific detection by mass spectrometry (HPLC/MS or LC/MS), and describes the theory and application of modern LC/MS in its most commonly employed configurations. Included are discussions of the most widely applied ionization processes for LC/MS, and the most useful and commonly used mass analyzers. Particular emphasis is given to HPLC method development, and the impact of employing LC/MS on the method development process. Also included, is a discussion of gas-phase ion chemistry and how chromatography parameters can be employed to manipulate gas-phase ion chemistry to enhance LC/MS analysis. Finally, the relatively new combination of liquid chromatography with nuclear magnetic resonance spectroscopy (LC/NMR) is described and discussed. This discussion includes a critical examination of the costs and benefits of LC/NMR relative to conventional “tube” NMR with off-line sample isolati...
Pharmaceutical Technology, 2002