Gabriel Giancaspro - Academia.edu (original) (raw)
Papers by Gabriel Giancaspro
AMA Journal of Ethics
Increase in dietary supplement use in the United States suggests a great need for clinicians to b... more Increase in dietary supplement use in the United States suggests a great need for clinicians to be aware of the range of supplements' quality parameters. Regulatory requirements exist, but specific quality parameters for each ingredient are not set by regulators. This article considers how clinicians can evaluate dietary supplement product quality, assess manufacturers' adherence to public quality standards, and encourage use of verification and certification programs. The American Medical Association designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™ available through the AMA Ed Hub TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Frontiers in Pharmacology
C. morifolium flower and C. indicum flower are two closely related herbal species with similar mo... more C. morifolium flower and C. indicum flower are two closely related herbal species with similar morphological and microscopic characteristics but are discriminated in edible and medicinal purpose. However, there is no effective approach to distinguish the two herbs. A novel workflow for quickly differentiating C. morifolium flower and C. indicum flower was developed. Firstly, the difference in anti-inflammatory effects for C. morifolium flower and C. indicum flower was characterized using lipopolysaccharide-treated rats. Then HPLC fingerprint analysis for 53 batches of C. morifolium flowers and 33 batches of C. indicum flower was carried out to deep profile the chemical components. The preliminary markers were screened out by OPLS-DA, identified by HPLC-ESI-QTOF-MS, and quantified by the improved SSDMC (single reference standard to determine multiple compounds) approach. Finally, multiple statistical data mining was performed to confirm the markers and a binary logistic regression eq...
The Development of Pharmacopeial Monographs in the USP Herbal Medicines Compendium
Journal of Ravishankar University, Jul 1, 2016
Pharmaceutical analysis by NMR can accommodate strict impurity thresholds: The case of choline
Journal of Pharmaceutical and Biomedical Analysis, 2022
The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at th... more The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at the level of 0.05% or 0.03% (w/w) depending on the maximum daily intake. Therefore, any instrumental method of analysis applicable to the impurity analysis should be able to detect and quantify the analytes at those levels. This investigation was designed to verify the suitability of 1H NMR spectroscopy for the detection of impurities, as a first step in the process before attempting quantification. In order to minimize demand on equipment, this study employed a 400 MHz instrument for structural confirmation and signal assignments of choline (1) and O-(2-hydroxyethyl)choline (2), a known impurity. The limit of detection (LOD) of 2 in 10 mg of 1 was established as 0.01% on a 400 MHz instrument and 2% on a 60 MHz (benchtop) NMR spectrometer. Thus, impurities for which quantification is required are readily detected at 400 MHz or above. These results are in contrast to the widespread belief that 1H NMR sensitivity is insufficient for pharmaceutical impurity analysis. The choice of solvent was recognized as a critical parameter for 1H NMR LOD analysis. Furthermore, publicly available NMR raw data (HMDB) proved to be valuable for unveiling the otherwise cryptic information hidden in complex signal patterns via 1H NMR iterative Full Spin Analysis. Finally, the study uncovered the less noticed, yet characteristic, 14N-1H coupling in the -N+(CH3)3 groups, adding strong arguments for the Raw NMR Data Initiative. Collectively, the data prove that the analytical capabilities of high-field NMR easily fulfill the ICH requirements for detection of impurity in the presence of an actual substance of interest which makes it a step closer to achieving regulatory standards.
Journal of Dietary Supplements, 2020
Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight... more Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight loss, and to maintain health. Adverse events, including cardiovascular (CV) effects, have been reported in military personnel taking supplements. Previous research determined that ingestion of multi-ingredient dietary supplements (MIDS), can lead to signals of safety concerns. Therefore, to assess the safety of MIDS, the Department of Defense via a contractor explored the development of a model-based risk assessment tool. We present a strategy and preliminary novel multi-criteria decision analysis (MCDA)-based tool for assessing the risk of adverse CV effects from MIDS. The tool integrates toxicology and other relevant data available on MIDS; likelihood of exposure, and biologic plausibility that could contribute to specific aspects of risk. Inputs for the model are values of four measures assigned based on the available evidence supplemented with the opinion of experts in toxicology, modeling, risk assessment etc. Measures were weighted based on the experts' assessment of measures' relative importance. Finally, all data for the four measures were integrated to provide a risk potential of 0 (low risk) to 100 (high risk) that defines the relative risk of a MIDS to cause adverse reactions. We conclude that the best available evidence must be supplemented with the opinion of experts in medicine, toxicology and pharmacology. Model-based approaches are useful to inform risk assessment in the absence of data. This MCDA model provides a foundation for refinement and validation of accuracy of the model predictions as new evidence becomes available.
The development of botanical dietary supplement monographs
Tools to Fight Food Fraud
Economically motivated adulteration of food ingredients and dietary supplements shows no end in s... more Economically motivated adulteration of food ingredients and dietary supplements shows no end in sight, but new tools point to progress in detection.
Improving Krill Oil Standards
A krill oil monograph will improve identity and purity testing, and help curtail adulteration.
Journal of Natural Products, 2021
The present study demonstrates the relationship between conventional and quantum mechanical (QM) ... more The present study demonstrates the relationship between conventional and quantum mechanical (QM) NMR spectroscopic analyses, shown here to assist in building a convincingly orthogonal platform for the solution and documentation of demanding structures. Kaempferol-3-O-robinoside-7-Oglucoside, a bisdesmosidic flavonol triglycoside and botanical marker for the aerial parts of Withania somnifera, served as an exemplary case. As demonstrated, QM-based 1 H iterative full spin analysis (HiFSA) advances the understanding of both individual nuclear resonance spin patterns and the entire 1 H NMR spectrum of a molecule and establishes structurally determinant, numerical HiFSA profiles. The combination of HiFSA with regular 1D 1 H NMR spectra allows for simplified yet specific identification tests via comparison of high-quality experimental with QM-calculated spectra. HiFSA accounts for all features encountered in 1 H NMR spectra: nonlinear high-order effects, complex multiplets, and their usually overlapped signals. As HiFSA replicates spectrum patterns from field-independent parameters with high accuracy, this methodology can be ported to low-field NMR instruments (40−100 MHz). With its reliance on experimental NMR evidence, the QM approach builds up confidence in structural characterization and potentially reduces identity analyses to simple 1D 1 H NMR experiments. This approach may lead to efficient implementation of conclusive identification tests in pharmacopeial and regulatory analyses: from simple organics to complex natural products.
Toxicology Reports, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Clinical Pharmacology & Therapeutics, 2018
The United States Pharmacopeia (USP) is an independent, nonprofit, science‐based organization who... more The United States Pharmacopeia (USP) is an independent, nonprofit, science‐based organization whose mission is to improve global health through public quality standards for dietary supplements, medicines, and food ingredients.1 Before developing standards for dietary supplement ingredients, the USP performs an “Admission Evaluation” (Figure 1), which includes an assessment to ascertain that an ingredient does not present a serious health risk.2 This article discusses the challenges encountered during the evaluation of botanicals and proposes possible solutions.
AOAC SMPR 2014.007: Authentication of Selected Vaccinium species (Anthocyanins) in Dietary Ingredients and Dietary Supplements
Journal of AOAC International, 2015
Use of qNMR to determine HPLC relative response factors for botanical reference standards used in pharmacopeial monographs
Journal of Pharmaceutical and Biomedical Analysis, 2022
In modern botanical pharmacopeial monographs, one measurement of content is the quantitation of r... more In modern botanical pharmacopeial monographs, one measurement of content is the quantitation of relevant constituents as marker compounds. The use of suitable reference standards (RSs) to quantify multiple compounds by HPLC is recommended in the U.S. Pharmacopeial (USP) botanical monographs. However, these substances may be expensive and difficult to develop into an RS. Surrogate RSs could be used instead of the actual constituents, provided that the relative response factors (RRFs) of each analyte to the selected surrogate RS are known. USP monographs of both Sichuan Lovage Rhizome and Dong Quai Root recognize Z-ligustilide as a major characteristic marker compound, making quantitation of Z-ligustilide and its analog(s) relevant for quality control. However, because Z-ligustilide is unstable, it is difficult to develop it into a quantitative RS. Instead, oxybenzone was selected as a surrogate external quantitative RS because of its similar chromatographic behavior to Z-ligustilide, its stability, and affordable cost. The RRF determination of Z-ligustilide to oxybenzone by the conventional HPLC procedure is challenging due to both the instability of the purified Z-ligustilide at ambient temperature and the difficulty of determining its purity. Therefore, a qNMR method was used to overcome these challenges as it enables to directly measure the mass ratio of Z-ligustilide to oxybenzone in the stock solution without the need for weighing and purity information. In the present study, RRF values of 1.01, 0.46, and 0.89 for Z-ligustilide, senkyunolide A, and ferulic acid relative to oxybenzone, respectively, were determined using the qNMR-based methodology.
Frontiers in Pharmacology
Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality p... more Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality parameters for each component used in the manufacture of a dietary supplement to ensure that specifications for the identity, purity, strength, composition, and limits on contaminants are met.* Compliance with botanical extract ingredient specifications is assured by using scientifically valid methods of analysis, the results of which are reported on certificates of analysis (CoAs). However, CoAs routinely include additional data that are not amenable to verification through methods of analysis. Such descriptive information may include Plant to Extract ratios, which are ratios of the quantity of botanical article used in the manufacture of the extract to the quantity of extract obtained. Plant to Extract ratios can be misleading when their meaning is not clearly understood.Plant to Extract ratios do not completely describe botanical extracts because other important factors influence the m...
Phytomedicine, 2018
Background: In order to define appropriate quality of botanical dietary supplements, botanical dr... more Background: In order to define appropriate quality of botanical dietary supplements, botanical drugs, and herbal medicines, the United States Pharmacopeia (USP) and the Herbal Medicines Compendium (HMC) contain science-based quality standards that include multiple interrelated tests to provide a full quality characterization for each article in terms of its identity, purity, and content. Purpose: To provide a comprehensive description of the pharmacopeial tests and requirements for articles of botanical origin in the aforementioned compendia. Selective chromatographic procedures, such as high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC), are used as Identification tests in pharmacopeial monographs to detect species substitution or other confounders. HPLC quantitative tests are typically used to determine the content of key constituents, i.e., the total or individual amount of plant secondary metabolites that are considered bioactive constituents or analytical marker compounds. Purity specifications are typically set to limit the content of contaminants such as toxic elements, pesticides, and fungal toxins. Additional requirements highlight the importance of naming, definition, use of reference materials, and packaging/storage conditions. Methods: Technical requirements for each section of the monographs were illustrated with specific examples. Tests were performed on authentic samples using pharmacopeial reference standards. The chromatographic analytical procedures were validated to provide characteristic profiles for the identity and/or accurate determination of the content of quality markers. Results: The multiple tests included in each monograph complement each other to provide an appropriate pharmacopeial quality characterization for the botanicals used as herbal medicines and dietary supplements. The monographs provide detailed specifications for identity, content of bioactive constituents or quality markers, and limits of contaminants, adulterants, and potentially toxic substances. Additional requirements such as labeling and packaging further contribute to preserve the quality of these products. Conclusion: Compliance with pharmacopeial specifications should be required to ensure the reliability of botanical articles used for health care purposes.
The Journal of nutrition, 2016
The increasing consumption of amino acids from a wide variety of sources, including dietary suppl... more The increasing consumption of amino acids from a wide variety of sources, including dietary supplements, natural health products, medical foods, infant formulas, athletic and work-out products, herbal medicines, and other national and international categories of nutritional and functional food products, increases the exposure to amino acids to amounts far beyond those normally obtained from the diet, thereby necessitating appropriate and robust safety assessments of these ingredients. Safety assessments of amino acids, similar to all food constituents, largely rely on the establishment of an upper limit [Tolerable Upper Intake Level (UL)] considered to be a guide for avoiding high intake, above which adverse or toxic effects might occur. However, reliable ULs have been difficult or impossible to define for amino acids because of inadequate toxicity studies in animals and scarce or missing clinical data, as well as a paucity or absence of adverse event reporting data. This review exa...
High Performance Liquid Chromatographic Determination of Sodium Cromoglycate
Drug Development and Industrial Pharmacy
ABSTRACT
Pharmacoepidemiology and Drug Safety, 2012
The review by Teschke et al. 1 reanalyzed a selected group of 22 spontaneous reports from regulat... more The review by Teschke et al. 1 reanalyzed a selected group of 22 spontaneous reports from regulatory agencies for the causal relationship between the use of black cohosh-containing products and hepatotoxicity and concluded that an "updated" Council for International Organizations of Medical Sciences (CIOMS) scale should replace the liver-unspecific Naranjo scale. The "update" referred to by the author is not originated by the CIOMS but includes the authors' modifications to the scale. On the basis of their new approach, the authors conclude that causality for black cohoshmediated liver damage is "unlikely or excluded." We would like to draw attention to some of the fundamental flaws with the authors' analysis:
Maturitas, 2010
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:
Journal of Pharmaceutical and Biomedical Analysis, 2019
Whereas generic, LC-based pharmaceutical control quality measures depend largely on the detection... more Whereas generic, LC-based pharmaceutical control quality measures depend largely on the detection mode and can be particularly 'blind' to certain impurities, NMR is a more versatile and, thus, often more judicious detector. While adulteration presents ever-evolving challenges for the analysis of active pharmaceutical ingredients (APIs) and finished products sold in the worldwide (online) marketplace, research chemicals are usually trusted rather than being considered flawed or even adulterated. This report shows how NMR analysis uncovered the unanticipated presence of substantial amounts of mannitol (20 and 43% w/w) as undeclared constituent in two custom synthetic peptides, DR and DRVYI, that were sourced commercially. Quantitative 1 H NMR (qHNMR) readily detected the *
AMA Journal of Ethics
Increase in dietary supplement use in the United States suggests a great need for clinicians to b... more Increase in dietary supplement use in the United States suggests a great need for clinicians to be aware of the range of supplements' quality parameters. Regulatory requirements exist, but specific quality parameters for each ingredient are not set by regulators. This article considers how clinicians can evaluate dietary supplement product quality, assess manufacturers' adherence to public quality standards, and encourage use of verification and certification programs. The American Medical Association designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 Credit™ available through the AMA Ed Hub TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
Frontiers in Pharmacology
C. morifolium flower and C. indicum flower are two closely related herbal species with similar mo... more C. morifolium flower and C. indicum flower are two closely related herbal species with similar morphological and microscopic characteristics but are discriminated in edible and medicinal purpose. However, there is no effective approach to distinguish the two herbs. A novel workflow for quickly differentiating C. morifolium flower and C. indicum flower was developed. Firstly, the difference in anti-inflammatory effects for C. morifolium flower and C. indicum flower was characterized using lipopolysaccharide-treated rats. Then HPLC fingerprint analysis for 53 batches of C. morifolium flowers and 33 batches of C. indicum flower was carried out to deep profile the chemical components. The preliminary markers were screened out by OPLS-DA, identified by HPLC-ESI-QTOF-MS, and quantified by the improved SSDMC (single reference standard to determine multiple compounds) approach. Finally, multiple statistical data mining was performed to confirm the markers and a binary logistic regression eq...
The Development of Pharmacopeial Monographs in the USP Herbal Medicines Compendium
Journal of Ravishankar University, Jul 1, 2016
Pharmaceutical analysis by NMR can accommodate strict impurity thresholds: The case of choline
Journal of Pharmaceutical and Biomedical Analysis, 2022
The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at th... more The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at the level of 0.05% or 0.03% (w/w) depending on the maximum daily intake. Therefore, any instrumental method of analysis applicable to the impurity analysis should be able to detect and quantify the analytes at those levels. This investigation was designed to verify the suitability of 1H NMR spectroscopy for the detection of impurities, as a first step in the process before attempting quantification. In order to minimize demand on equipment, this study employed a 400 MHz instrument for structural confirmation and signal assignments of choline (1) and O-(2-hydroxyethyl)choline (2), a known impurity. The limit of detection (LOD) of 2 in 10 mg of 1 was established as 0.01% on a 400 MHz instrument and 2% on a 60 MHz (benchtop) NMR spectrometer. Thus, impurities for which quantification is required are readily detected at 400 MHz or above. These results are in contrast to the widespread belief that 1H NMR sensitivity is insufficient for pharmaceutical impurity analysis. The choice of solvent was recognized as a critical parameter for 1H NMR LOD analysis. Furthermore, publicly available NMR raw data (HMDB) proved to be valuable for unveiling the otherwise cryptic information hidden in complex signal patterns via 1H NMR iterative Full Spin Analysis. Finally, the study uncovered the less noticed, yet characteristic, 14N-1H coupling in the -N+(CH3)3 groups, adding strong arguments for the Raw NMR Data Initiative. Collectively, the data prove that the analytical capabilities of high-field NMR easily fulfill the ICH requirements for detection of impurity in the presence of an actual substance of interest which makes it a step closer to achieving regulatory standards.
Journal of Dietary Supplements, 2020
Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight... more Military personnel use dietary supplements (DS) for performance enhancement, bodybuilding, weight loss, and to maintain health. Adverse events, including cardiovascular (CV) effects, have been reported in military personnel taking supplements. Previous research determined that ingestion of multi-ingredient dietary supplements (MIDS), can lead to signals of safety concerns. Therefore, to assess the safety of MIDS, the Department of Defense via a contractor explored the development of a model-based risk assessment tool. We present a strategy and preliminary novel multi-criteria decision analysis (MCDA)-based tool for assessing the risk of adverse CV effects from MIDS. The tool integrates toxicology and other relevant data available on MIDS; likelihood of exposure, and biologic plausibility that could contribute to specific aspects of risk. Inputs for the model are values of four measures assigned based on the available evidence supplemented with the opinion of experts in toxicology, modeling, risk assessment etc. Measures were weighted based on the experts' assessment of measures' relative importance. Finally, all data for the four measures were integrated to provide a risk potential of 0 (low risk) to 100 (high risk) that defines the relative risk of a MIDS to cause adverse reactions. We conclude that the best available evidence must be supplemented with the opinion of experts in medicine, toxicology and pharmacology. Model-based approaches are useful to inform risk assessment in the absence of data. This MCDA model provides a foundation for refinement and validation of accuracy of the model predictions as new evidence becomes available.
The development of botanical dietary supplement monographs
Tools to Fight Food Fraud
Economically motivated adulteration of food ingredients and dietary supplements shows no end in s... more Economically motivated adulteration of food ingredients and dietary supplements shows no end in sight, but new tools point to progress in detection.
Improving Krill Oil Standards
A krill oil monograph will improve identity and purity testing, and help curtail adulteration.
Journal of Natural Products, 2021
The present study demonstrates the relationship between conventional and quantum mechanical (QM) ... more The present study demonstrates the relationship between conventional and quantum mechanical (QM) NMR spectroscopic analyses, shown here to assist in building a convincingly orthogonal platform for the solution and documentation of demanding structures. Kaempferol-3-O-robinoside-7-Oglucoside, a bisdesmosidic flavonol triglycoside and botanical marker for the aerial parts of Withania somnifera, served as an exemplary case. As demonstrated, QM-based 1 H iterative full spin analysis (HiFSA) advances the understanding of both individual nuclear resonance spin patterns and the entire 1 H NMR spectrum of a molecule and establishes structurally determinant, numerical HiFSA profiles. The combination of HiFSA with regular 1D 1 H NMR spectra allows for simplified yet specific identification tests via comparison of high-quality experimental with QM-calculated spectra. HiFSA accounts for all features encountered in 1 H NMR spectra: nonlinear high-order effects, complex multiplets, and their usually overlapped signals. As HiFSA replicates spectrum patterns from field-independent parameters with high accuracy, this methodology can be ported to low-field NMR instruments (40−100 MHz). With its reliance on experimental NMR evidence, the QM approach builds up confidence in structural characterization and potentially reduces identity analyses to simple 1D 1 H NMR experiments. This approach may lead to efficient implementation of conclusive identification tests in pharmacopeial and regulatory analyses: from simple organics to complex natural products.
Toxicology Reports, 2020
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Clinical Pharmacology & Therapeutics, 2018
The United States Pharmacopeia (USP) is an independent, nonprofit, science‐based organization who... more The United States Pharmacopeia (USP) is an independent, nonprofit, science‐based organization whose mission is to improve global health through public quality standards for dietary supplements, medicines, and food ingredients.1 Before developing standards for dietary supplement ingredients, the USP performs an “Admission Evaluation” (Figure 1), which includes an assessment to ascertain that an ingredient does not present a serious health risk.2 This article discusses the challenges encountered during the evaluation of botanicals and proposes possible solutions.
AOAC SMPR 2014.007: Authentication of Selected Vaccinium species (Anthocyanins) in Dietary Ingredients and Dietary Supplements
Journal of AOAC International, 2015
Use of qNMR to determine HPLC relative response factors for botanical reference standards used in pharmacopeial monographs
Journal of Pharmaceutical and Biomedical Analysis, 2022
In modern botanical pharmacopeial monographs, one measurement of content is the quantitation of r... more In modern botanical pharmacopeial monographs, one measurement of content is the quantitation of relevant constituents as marker compounds. The use of suitable reference standards (RSs) to quantify multiple compounds by HPLC is recommended in the U.S. Pharmacopeial (USP) botanical monographs. However, these substances may be expensive and difficult to develop into an RS. Surrogate RSs could be used instead of the actual constituents, provided that the relative response factors (RRFs) of each analyte to the selected surrogate RS are known. USP monographs of both Sichuan Lovage Rhizome and Dong Quai Root recognize Z-ligustilide as a major characteristic marker compound, making quantitation of Z-ligustilide and its analog(s) relevant for quality control. However, because Z-ligustilide is unstable, it is difficult to develop it into a quantitative RS. Instead, oxybenzone was selected as a surrogate external quantitative RS because of its similar chromatographic behavior to Z-ligustilide, its stability, and affordable cost. The RRF determination of Z-ligustilide to oxybenzone by the conventional HPLC procedure is challenging due to both the instability of the purified Z-ligustilide at ambient temperature and the difficulty of determining its purity. Therefore, a qNMR method was used to overcome these challenges as it enables to directly measure the mass ratio of Z-ligustilide to oxybenzone in the stock solution without the need for weighing and purity information. In the present study, RRF values of 1.01, 0.46, and 0.89 for Z-ligustilide, senkyunolide A, and ferulic acid relative to oxybenzone, respectively, were determined using the qNMR-based methodology.
Frontiers in Pharmacology
Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality p... more Dietary supplement current good manufacturing practice (cGMP) requires establishment of quality parameters for each component used in the manufacture of a dietary supplement to ensure that specifications for the identity, purity, strength, composition, and limits on contaminants are met.* Compliance with botanical extract ingredient specifications is assured by using scientifically valid methods of analysis, the results of which are reported on certificates of analysis (CoAs). However, CoAs routinely include additional data that are not amenable to verification through methods of analysis. Such descriptive information may include Plant to Extract ratios, which are ratios of the quantity of botanical article used in the manufacture of the extract to the quantity of extract obtained. Plant to Extract ratios can be misleading when their meaning is not clearly understood.Plant to Extract ratios do not completely describe botanical extracts because other important factors influence the m...
Phytomedicine, 2018
Background: In order to define appropriate quality of botanical dietary supplements, botanical dr... more Background: In order to define appropriate quality of botanical dietary supplements, botanical drugs, and herbal medicines, the United States Pharmacopeia (USP) and the Herbal Medicines Compendium (HMC) contain science-based quality standards that include multiple interrelated tests to provide a full quality characterization for each article in terms of its identity, purity, and content. Purpose: To provide a comprehensive description of the pharmacopeial tests and requirements for articles of botanical origin in the aforementioned compendia. Selective chromatographic procedures, such as high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC), are used as Identification tests in pharmacopeial monographs to detect species substitution or other confounders. HPLC quantitative tests are typically used to determine the content of key constituents, i.e., the total or individual amount of plant secondary metabolites that are considered bioactive constituents or analytical marker compounds. Purity specifications are typically set to limit the content of contaminants such as toxic elements, pesticides, and fungal toxins. Additional requirements highlight the importance of naming, definition, use of reference materials, and packaging/storage conditions. Methods: Technical requirements for each section of the monographs were illustrated with specific examples. Tests were performed on authentic samples using pharmacopeial reference standards. The chromatographic analytical procedures were validated to provide characteristic profiles for the identity and/or accurate determination of the content of quality markers. Results: The multiple tests included in each monograph complement each other to provide an appropriate pharmacopeial quality characterization for the botanicals used as herbal medicines and dietary supplements. The monographs provide detailed specifications for identity, content of bioactive constituents or quality markers, and limits of contaminants, adulterants, and potentially toxic substances. Additional requirements such as labeling and packaging further contribute to preserve the quality of these products. Conclusion: Compliance with pharmacopeial specifications should be required to ensure the reliability of botanical articles used for health care purposes.
The Journal of nutrition, 2016
The increasing consumption of amino acids from a wide variety of sources, including dietary suppl... more The increasing consumption of amino acids from a wide variety of sources, including dietary supplements, natural health products, medical foods, infant formulas, athletic and work-out products, herbal medicines, and other national and international categories of nutritional and functional food products, increases the exposure to amino acids to amounts far beyond those normally obtained from the diet, thereby necessitating appropriate and robust safety assessments of these ingredients. Safety assessments of amino acids, similar to all food constituents, largely rely on the establishment of an upper limit [Tolerable Upper Intake Level (UL)] considered to be a guide for avoiding high intake, above which adverse or toxic effects might occur. However, reliable ULs have been difficult or impossible to define for amino acids because of inadequate toxicity studies in animals and scarce or missing clinical data, as well as a paucity or absence of adverse event reporting data. This review exa...
High Performance Liquid Chromatographic Determination of Sodium Cromoglycate
Drug Development and Industrial Pharmacy
ABSTRACT
Pharmacoepidemiology and Drug Safety, 2012
The review by Teschke et al. 1 reanalyzed a selected group of 22 spontaneous reports from regulat... more The review by Teschke et al. 1 reanalyzed a selected group of 22 spontaneous reports from regulatory agencies for the causal relationship between the use of black cohosh-containing products and hepatotoxicity and concluded that an "updated" Council for International Organizations of Medical Sciences (CIOMS) scale should replace the liver-unspecific Naranjo scale. The "update" referred to by the author is not originated by the CIOMS but includes the authors' modifications to the scale. On the basis of their new approach, the authors conclude that causality for black cohoshmediated liver damage is "unlikely or excluded." We would like to draw attention to some of the fundamental flaws with the authors' analysis:
Maturitas, 2010
This article appeared in a journal published by Elsevier. The attached copy is furnished to the a... more This article appeared in a journal published by Elsevier. The attached copy is furnished to the author for internal non-commercial research and education use, including for instruction at the authors institution and sharing with colleagues. Other uses, including reproduction and distribution, or selling or licensing copies, or posting to personal, institutional or third party websites are prohibited. In most cases authors are permitted to post their version of the article (e.g. in Word or Tex form) to their personal website or institutional repository. Authors requiring further information regarding Elsevier's archiving and manuscript policies are encouraged to visit:
Journal of Pharmaceutical and Biomedical Analysis, 2019
Whereas generic, LC-based pharmaceutical control quality measures depend largely on the detection... more Whereas generic, LC-based pharmaceutical control quality measures depend largely on the detection mode and can be particularly 'blind' to certain impurities, NMR is a more versatile and, thus, often more judicious detector. While adulteration presents ever-evolving challenges for the analysis of active pharmaceutical ingredients (APIs) and finished products sold in the worldwide (online) marketplace, research chemicals are usually trusted rather than being considered flawed or even adulterated. This report shows how NMR analysis uncovered the unanticipated presence of substantial amounts of mannitol (20 and 43% w/w) as undeclared constituent in two custom synthetic peptides, DR and DRVYI, that were sourced commercially. Quantitative 1 H NMR (qHNMR) readily detected the *