Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00381
E. Kellenbach, T. Rundlöf
This chapter describes the application of NMR spectroscopy to the determination of the identity, content, structure and purity of peptides. Both 1D and 2D NMR examples are presented for both 1H and other nuclei. NMR spectroscopy is a nondestructive technique requiring limited sample pretreatment and development time. The limited sample pretreatment reduces the experimental time and variations due to handling, thereby increasing robustness. NMR spectroscopy can distinguish between very closely related peptides. It is especially suited for the determination of unrelated impurities such as process-related impurities and extractables/leachables. NMR spectroscopy is very sensitive to higher-order structure. Although NMR equipment in itself is expensive, the actual cost of an NMR spectrum is low owing to automation and limited consumables.
{"title":"Chapter 11. Determination of the Identity, Content and Purity of Therapeutic Peptides by NMR Spectroscopy","authors":"E. Kellenbach, T. Rundlöf","doi":"10.1039/9781788016445-00381","DOIUrl":"https://doi.org/10.1039/9781788016445-00381","url":null,"abstract":"This chapter describes the application of NMR spectroscopy to the determination of the identity, content, structure and purity of peptides. Both 1D and 2D NMR examples are presented for both 1H and other nuclei. NMR spectroscopy is a nondestructive technique requiring limited sample pretreatment and development time. The limited sample pretreatment reduces the experimental time and variations due to handling, thereby increasing robustness. NMR spectroscopy can distinguish between very closely related peptides. It is especially suited for the determination of unrelated impurities such as process-related impurities and extractables/leachables. NMR spectroscopy is very sensitive to higher-order structure. Although NMR equipment in itself is expensive, the actual cost of an NMR spectrum is low owing to automation and limited consumables.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"72 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81109059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00503
Jyothi Thundimadathil
Delivery of peptide drugs using microspheres has been used in a number of commercial drug formulations and this area continues to grow to overcome potential challenges with the intrinsic properties of peptides and proteins. The use of microparticles as an alternative delivery system for peptide and protein drugs has attracted substantial interest in recent years. Encapsulation of peptides or proteins in such carrier systems during formulation could potentially benefit the drug profile. Several examples of peptide and protein delivery using microsphere formulations are included. Different types of microspheres, their preparation, characterization, factors affecting drug delivery and mechanism of drug delivery are discussed. Peptide drugs on the market such as leuprolide, triptorelin, octreotide, lanreotide, human growth hormone, buserelin, abarelix and exenatide use microsphere-based formulations. Drug nanoparticle formulations have been demonstrated to show increased solubility and thus enhanced bioavailability, with additional ability to cross the blood–brain barrier, enter the pulmonary system and be absorbed through the tight junctions of endothelial cells of the skin, primarily owing to their small size and large surface area. Nanoparticle formulations based on liposomes, polymeric micelles, polymeric nanoparticles, nanoemulsions, nanogels, dendrimers, fullerenes, carbon nanotubes, magnetic nanoparticles, metal nanoparticles and quantum dots have been extensively discussed in the literature. Selected examples of peptide/protein nanoparticle formulations are discussed with special emphasis on various delivery routes and delivery mechanisms.
{"title":"Chapter 14. Formulations of Microspheres and Nanoparticles for Peptide Delivery","authors":"Jyothi Thundimadathil","doi":"10.1039/9781788016445-00503","DOIUrl":"https://doi.org/10.1039/9781788016445-00503","url":null,"abstract":"Delivery of peptide drugs using microspheres has been used in a number of commercial drug formulations and this area continues to grow to overcome potential challenges with the intrinsic properties of peptides and proteins. The use of microparticles as an alternative delivery system for peptide and protein drugs has attracted substantial interest in recent years. Encapsulation of peptides or proteins in such carrier systems during formulation could potentially benefit the drug profile. Several examples of peptide and protein delivery using microsphere formulations are included. Different types of microspheres, their preparation, characterization, factors affecting drug delivery and mechanism of drug delivery are discussed. Peptide drugs on the market such as leuprolide, triptorelin, octreotide, lanreotide, human growth hormone, buserelin, abarelix and exenatide use microsphere-based formulations. Drug nanoparticle formulations have been demonstrated to show increased solubility and thus enhanced bioavailability, with additional ability to cross the blood–brain barrier, enter the pulmonary system and be absorbed through the tight junctions of endothelial cells of the skin, primarily owing to their small size and large surface area. Nanoparticle formulations based on liposomes, polymeric micelles, polymeric nanoparticles, nanoemulsions, nanogels, dendrimers, fullerenes, carbon nanotubes, magnetic nanoparticles, metal nanoparticles and quantum dots have been extensively discussed in the literature. Selected examples of peptide/protein nanoparticle formulations are discussed with special emphasis on various delivery routes and delivery mechanisms.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"14 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87642475","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00194
Aleksander Świetłow, Asher Lower
The goal of consistently achieving critical quality attributes (CQAs) for synthetic peptide active pharmaceutical ingredients (APIs) may be challenging owing to the complexity of the manufacturing process and the large number of potential sources of variability. This chapter outlines the principles of process design and the development of a comprehensive control strategy for manufacturing peptide APIs of consistent quality. A approach is described that involves process design utilizing a practical application of quality target product profile (QTPP), quality-by-design (QbD), identification and mitigation of risks and process characterization. The parallel development of supporting analytical tools requires the development of a testing strategy that encompasses all stages of manufacturing from starting materials, in-process testing through drug substance release testing and stability testing. Phase-appropriate approaches to synthetic, hybrid and semisynthetic technologies used for manufacturing peptides are discussed.
{"title":"Chapter 7. A Holistic Quality Control Strategy for Peptide Active Pharmaceutical Ingredients (APIs)","authors":"Aleksander Świetłow, Asher Lower","doi":"10.1039/9781788016445-00194","DOIUrl":"https://doi.org/10.1039/9781788016445-00194","url":null,"abstract":"The goal of consistently achieving critical quality attributes (CQAs) for synthetic peptide active pharmaceutical ingredients (APIs) may be challenging owing to the complexity of the manufacturing process and the large number of potential sources of variability. This chapter outlines the principles of process design and the development of a comprehensive control strategy for manufacturing peptide APIs of consistent quality. A approach is described that involves process design utilizing a practical application of quality target product profile (QTPP), quality-by-design (QbD), identification and mitigation of risks and process characterization. The parallel development of supporting analytical tools requires the development of a testing strategy that encompasses all stages of manufacturing from starting materials, in-process testing through drug substance release testing and stability testing. Phase-appropriate approaches to synthetic, hybrid and semisynthetic technologies used for manufacturing peptides are discussed.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"58 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88646307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00097
Prem Ramiya
Chemistry, manufacturing and controls (CMC) for active pharmaceutical ingredients (APIs) and drug products (DPs) consists in understanding the chemistry behind the manufacturing process, in-process controls, acceptance criteria for drug substances and DPs and supporting stability studies. Guidance documents from the US Food and Drug Administration (FDA) and International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) assist novice readers with how to implement most of the CMC-related activities during development and commercialization activities. The development process for APIs and DPs follows the traditional approach of preclinical, Phase I (safety), Phase II (efficacy) and Phase III (statistical significance over existing therapy) and then final approval after filing a New Drug Application (NDA) by the FDA or marketing approval in the European Union (EU). This chapter (a) summarizes the CMC topics for APIs and DPs in general and (b) narrates the distinct activities required in each phase of development as the molecule progresses from early development to commercialization.
{"title":"Chapter 4. Chemistry, Manufacturing and Controls: Active Pharmaceutical Ingredient and Drug Product","authors":"Prem Ramiya","doi":"10.1039/9781788016445-00097","DOIUrl":"https://doi.org/10.1039/9781788016445-00097","url":null,"abstract":"Chemistry, manufacturing and controls (CMC) for active pharmaceutical ingredients (APIs) and drug products (DPs) consists in understanding the chemistry behind the manufacturing process, in-process controls, acceptance criteria for drug substances and DPs and supporting stability studies. Guidance documents from the US Food and Drug Administration (FDA) and International Council on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) assist novice readers with how to implement most of the CMC-related activities during development and commercialization activities. The development process for APIs and DPs follows the traditional approach of preclinical, Phase I (safety), Phase II (efficacy) and Phase III (statistical significance over existing therapy) and then final approval after filing a New Drug Application (NDA) by the FDA or marketing approval in the European Union (EU). This chapter (a) summarizes the CMC topics for APIs and DPs in general and (b) narrates the distinct activities required in each phase of development as the molecule progresses from early development to commercialization.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"7 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88217681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00421
T. Sawyer, J. Hochman, Suzanne M. D'Addio, B. Sherborne, Marian E. Gindy
The biopharmaceutical industry is experiencing renewed interest in the discovery and development of peptide therapeutics, enabled in part by advances in synthetic processes, phage display technologies and combinatorial libraries that have permitted the rapid design, identification and evaluation of potential new peptide actives. With more than 100 peptide drugs already on the market as of 2018, garnering collective sales in excess of $20 billion, the promise of peptide medicines is a compelling one. Yet broad realization of peptide drugs remains elusive: limitations in biological delivery, including short half-life, rapid metabolism, proteolytic cleavage, poor permeation across biological membranes and a propensity for chemical and physical degradation, present significant challenges to peptide drug development. This chapter addresses key stability and pharmacokinetic considerations for the development of peptide drugs, identifies approaches and methodologies for their assessments in preclinical research and development and discusses current and emerging chemistry strategies to address such liabilities through predictive molecular design.
{"title":"Chapter 12. Transport, Stability and Delivery Considerations for the Design of Peptide Drugs","authors":"T. Sawyer, J. Hochman, Suzanne M. D'Addio, B. Sherborne, Marian E. Gindy","doi":"10.1039/9781788016445-00421","DOIUrl":"https://doi.org/10.1039/9781788016445-00421","url":null,"abstract":"The biopharmaceutical industry is experiencing renewed interest in the discovery and development of peptide therapeutics, enabled in part by advances in synthetic processes, phage display technologies and combinatorial libraries that have permitted the rapid design, identification and evaluation of potential new peptide actives. With more than 100 peptide drugs already on the market as of 2018, garnering collective sales in excess of $20 billion, the promise of peptide medicines is a compelling one. Yet broad realization of peptide drugs remains elusive: limitations in biological delivery, including short half-life, rapid metabolism, proteolytic cleavage, poor permeation across biological membranes and a propensity for chemical and physical degradation, present significant challenges to peptide drug development. This chapter addresses key stability and pharmacokinetic considerations for the development of peptide drugs, identifies approaches and methodologies for their assessments in preclinical research and development and discusses current and emerging chemistry strategies to address such liabilities through predictive molecular design.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"27 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89668409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00069
A. Kaliyaperumal
Assessment of the immunogenicity of peptides used for therapeutic purposes along with measurement of their biological activity is essential to evaluating the safety of therapeutic peptides. Accurate determination of the potency (biological activity) and evaluation of the immunogenicity of peptide-based therapeutic drugs for use in humans are crucial to their efficacy and safety. The assays used in determining the biological activity must closely follow the mechanism of action. A panel of assays can be used for testing the activity of a molecule. Several cell-based assay methods with a wide range of readouts can be used in the evaluation. These readouts can be cellular responses, signal transduction events, gene transcription reporter assays and/or ligand–receptor-binding cell-based assays using flow cytometry. Additionally, it is important to evaluate the immunogenic potential of the biologics in an appropriate fashion using a clearly defined strategy and clinical trials. The studies must include the appropriate risk assessment procedures and evaluation of immunogenicity using validated methods. The immune responses against the therapeutic biologics can be studied using various methodologies. These include enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), chemiluminescence and flow cytometry assays for binding antibodies and cell-based assays for neutralizing antibodies. The immune responses to the biologics can vary widely in various cross-sections of the population, hence a combination of techniques is necessary to evaluate fully the immunogenic potential of the biologics. This chapter outlines various commonly used technology platforms and their merits and shortcomings.
{"title":"Chapter 3. Biological and Immunogenicity Evaluation Strategy for Therapeutic Peptides: Chemistry, Manufacturing and Controls Perspective","authors":"A. Kaliyaperumal","doi":"10.1039/9781788016445-00069","DOIUrl":"https://doi.org/10.1039/9781788016445-00069","url":null,"abstract":"Assessment of the immunogenicity of peptides used for therapeutic purposes along with measurement of their biological activity is essential to evaluating the safety of therapeutic peptides. Accurate determination of the potency (biological activity) and evaluation of the immunogenicity of peptide-based therapeutic drugs for use in humans are crucial to their efficacy and safety. The assays used in determining the biological activity must closely follow the mechanism of action. A panel of assays can be used for testing the activity of a molecule. Several cell-based assay methods with a wide range of readouts can be used in the evaluation. These readouts can be cellular responses, signal transduction events, gene transcription reporter assays and/or ligand–receptor-binding cell-based assays using flow cytometry. Additionally, it is important to evaluate the immunogenic potential of the biologics in an appropriate fashion using a clearly defined strategy and clinical trials. The studies must include the appropriate risk assessment procedures and evaluation of immunogenicity using validated methods. The immune responses against the therapeutic biologics can be studied using various methodologies. These include enzyme-linked immunosorbent assay (ELISA), surface plasmon resonance (SPR), chemiluminescence and flow cytometry assays for binding antibodies and cell-based assays for neutralizing antibodies. The immune responses to the biologics can vary widely in various cross-sections of the population, hence a combination of techniques is necessary to evaluate fully the immunogenic potential of the biologics. This chapter outlines various commonly used technology platforms and their merits and shortcomings.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"61 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87544735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00001
Larisa C Wu
The increasing interest of the pharmaceutical industry in peptide therapeutics has been a catalyst for the development of regulations in this area. Nevertheless, manufacturers and regulators continue to encounter scientific and regulatory challenges when dealing with peptides as active pharmaceutical ingredients in drug products. This chapter presents an up-to-date overview of the approval process for New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) as it pertains to peptide drugs at the US Food and Drug Administration (FDA). It also provides a structured summary of the quality considerations relevant to peptides. This includes unique characteristics concerning structurecharacterization, manufacturing, and impurities emerging from the manufacturing process or storage and their potential impact on peptide drug safety and efficacy.
{"title":"Chapter 1. Regulatory Considerations for Peptide Therapeutics","authors":"Larisa C Wu","doi":"10.1039/9781788016445-00001","DOIUrl":"https://doi.org/10.1039/9781788016445-00001","url":null,"abstract":"The increasing interest of the pharmaceutical industry in peptide therapeutics has been a catalyst for the development of regulations in this area. Nevertheless, manufacturers and regulators continue to encounter scientific and regulatory challenges when dealing with peptides as active pharmaceutical ingredients in drug products. This chapter presents an up-to-date overview of the approval process for New Drug Applications (NDAs) and Abbreviated New Drug Applications (ANDAs) as it pertains to peptide drugs at the US Food and Drug Administration (FDA). It also provides a structured summary of the quality considerations relevant to peptides. This includes unique characteristics concerning structurecharacterization, manufacturing, and impurities emerging from the manufacturing process or storage and their potential impact on peptide drug safety and efficacy.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"23 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85729566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00274
Renáta Varga, A. Rane
There is increased interest in peptides in pharmaceutical research and development owing to their superior characteristics over small molecules in terms of high selectivity, efficacy and safety and also over large biomolecules in terms of less complexity and the associated cost. However, peptides sit between these two well-studied and understood groups of therapeutics, challenging scientists in designing characterization and comparability studies to cover all analytical aspects. There is a vital part of chemistry, manufacturing and control (CMC) in peptide drug development describing the structure and characterization of the molecule itself and in the case of a generic development comparing its structure with that of a reference product. Considering the complexity in terms of multiple structural elements of peptides, similarly to proteins, these sections highlight the higher-order structure of peptides during development. This chapter focuses on the description of the higher-order structure elements of peptides and the potential analytical methodologies for characterization and to present the main differences and challenges when studying peptides compared with large proteins. At the end of the chapter, a recommended study design of higher-order structure characterization and comparability of generic peptides is presented. Note that in this chapter peptides are considered to be, by definition, to contain fewer than 100 amino acid residues and are well distinguished from proteins.
{"title":"Chapter 8. Higher-order Structure Characterization and Comparability Assessments for Peptides","authors":"Renáta Varga, A. Rane","doi":"10.1039/9781788016445-00274","DOIUrl":"https://doi.org/10.1039/9781788016445-00274","url":null,"abstract":"There is increased interest in peptides in pharmaceutical research and development owing to their superior characteristics over small molecules in terms of high selectivity, efficacy and safety and also over large biomolecules in terms of less complexity and the associated cost. However, peptides sit between these two well-studied and understood groups of therapeutics, challenging scientists in designing characterization and comparability studies to cover all analytical aspects. There is a vital part of chemistry, manufacturing and control (CMC) in peptide drug development describing the structure and characterization of the molecule itself and in the case of a generic development comparing its structure with that of a reference product. Considering the complexity in terms of multiple structural elements of peptides, similarly to proteins, these sections highlight the higher-order structure of peptides during development. This chapter focuses on the description of the higher-order structure elements of peptides and the potential analytical methodologies for characterization and to present the main differences and challenges when studying peptides compared with large proteins. At the end of the chapter, a recommended study design of higher-order structure characterization and comparability of generic peptides is presented. Note that in this chapter peptides are considered to be, by definition, to contain fewer than 100 amino acid residues and are well distinguished from proteins.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"17 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82006425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2019-08-16DOI: 10.1039/9781788016445-00313
K. Zeng, M. Boyne, Timothy K. Toby, C. Ruzicka
The suitability of a liquid chromatography–high-resolution mass spectrometry (LC–HRMS) method for monitoring peptide drug product quality is demonstrated on three case studies using the peptide drugs salmon calcitonin, bivalirudin and exenatide as model systems. LC–HRMS methods were able to provide qualitative information by characterizing the peptide structure and sequence and identifying peptide-related impurities. In addition, LC–HRMS methods can be used to obtain quantitative results with high selectivity, sensitivity, accuracy and precision and suitable linearity. Furthermore, LC–HRMS methods are advantageous because they have the ability to separate and detect low-level impurities where traditional high-performance liquid chromatography–UV detection (HPLC–UV) methods can lack the necessary specificity and sensitivity. Overall, LC–HRMS is an approach that can be used as part of the analytical framework to ensure proper quality control of peptide drug products including the assessment of peptide-related impurities.
{"title":"Chapter 9. Impurity Characterization and Quantification by Liquid Chromatography–High-resolution Mass Spectrometry","authors":"K. Zeng, M. Boyne, Timothy K. Toby, C. Ruzicka","doi":"10.1039/9781788016445-00313","DOIUrl":"https://doi.org/10.1039/9781788016445-00313","url":null,"abstract":"The suitability of a liquid chromatography–high-resolution mass spectrometry (LC–HRMS) method for monitoring peptide drug product quality is demonstrated on three case studies using the peptide drugs salmon calcitonin, bivalirudin and exenatide as model systems. LC–HRMS methods were able to provide qualitative information by characterizing the peptide structure and sequence and identifying peptide-related impurities. In addition, LC–HRMS methods can be used to obtain quantitative results with high selectivity, sensitivity, accuracy and precision and suitable linearity. Furthermore, LC–HRMS methods are advantageous because they have the ability to separate and detect low-level impurities where traditional high-performance liquid chromatography–UV detection (HPLC–UV) methods can lack the necessary specificity and sensitivity. Overall, LC–HRMS is an approach that can be used as part of the analytical framework to ensure proper quality control of peptide drug products including the assessment of peptide-related impurities.","PeriodicalId":20009,"journal":{"name":"Peptide Therapeutics","volume":"43 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79083124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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