Abstract
A major limitation of biological therapeutics is their propensity for degradation particularly in aqueous solutions hence resulting in their short shelf-life. In this study, the stability of trastuzumab (Herceptin®) intravenous (i.v.) solutions, an IgG1 monoclonal antibody (mAb), indicated for the treatment of HER2 positive breast cancer, stored under refrigerated conditions, was evaluated over 28 days. No change in visual appearance or average particle size was observed. The pH values of the trastuzumab i.v. solutions remained stable over time. Interestingly, no change in trastuzumab monomer concentration was observed throughout the 28-day study, as determined by SEC-HPLC. SDSPAGE showed only a monomer band corresponding to the molecular weight of trastuzumab. Circular dichroism spectra obtained following 28-day storage demonstrated integrity of the secondary structural conformation of trastuzumab. Results from this study show that trastuzumab i.v. solutions remain physically and structurally stable on storage at 2-8°C for 28 days. These findings suggest that trastuzumab in solution may not be as sensitive to degradation as expected for a mAb and therefore may have important implications in extending trastuzumab shelf life for clinical use and reducing associated healthcare cost.
Keywords: Trastuzumab, stability, protein aggregation, SEC, particle size, SDS-PAGE, Circular dichroism
Current Pharmaceutical Biotechnology
Title:Physical and Structural Stability of the Monoclonal Antibody, Trastuzumab (Herceptin®), Intravenous Solutions
Volume: 14 Issue: 2
Author(s): Ritesh M. Pabari, Benedict Ryan, Wazir Ahmad and Zebunnissa Ramtoola
Affiliation:
Keywords: Trastuzumab, stability, protein aggregation, SEC, particle size, SDS-PAGE, Circular dichroism
Abstract: A major limitation of biological therapeutics is their propensity for degradation particularly in aqueous solutions hence resulting in their short shelf-life. In this study, the stability of trastuzumab (Herceptin®) intravenous (i.v.) solutions, an IgG1 monoclonal antibody (mAb), indicated for the treatment of HER2 positive breast cancer, stored under refrigerated conditions, was evaluated over 28 days. No change in visual appearance or average particle size was observed. The pH values of the trastuzumab i.v. solutions remained stable over time. Interestingly, no change in trastuzumab monomer concentration was observed throughout the 28-day study, as determined by SEC-HPLC. SDSPAGE showed only a monomer band corresponding to the molecular weight of trastuzumab. Circular dichroism spectra obtained following 28-day storage demonstrated integrity of the secondary structural conformation of trastuzumab. Results from this study show that trastuzumab i.v. solutions remain physically and structurally stable on storage at 2-8°C for 28 days. These findings suggest that trastuzumab in solution may not be as sensitive to degradation as expected for a mAb and therefore may have important implications in extending trastuzumab shelf life for clinical use and reducing associated healthcare cost.
Export Options
About this article
Cite this article as:
M. Pabari Ritesh, Ryan Benedict, Ahmad Wazir and Ramtoola Zebunnissa, Physical and Structural Stability of the Monoclonal Antibody, Trastuzumab (Herceptin®), Intravenous Solutions, Current Pharmaceutical Biotechnology 2013; 14 (2) . https://dx.doi.org/10.2174/1389201011314020012
DOI https://dx.doi.org/10.2174/1389201011314020012 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Melatonin and Hypothalamic-Pituitary-Gonadal Axis
Current Medicinal Chemistry GSK-3 Inhibitors in the Regulation and Control of Colon Carcinoma
Current Drug Targets Mammalian DNA (Cytosine-5) Methyltransferase Mechanisms and RNA-Mediated Inhibition for Future Therapies
Epigenetic Diagnosis & Therapy (Discontinued) New Molecules as Drug Candidates for the Treatment of Upper and Lower GI Tract Ulcers
Current Pharmaceutical Design Cyclin Dependent Kinase 1 Inhibitors: A Review of Recent Progress
Current Medicinal Chemistry Leptin Signaling: A Key Pathway in Immune Responses
Current Signal Transduction Therapy Microsphere Technology for Chemotherapy of Mycobacterial Infections
Current Pharmaceutical Design Lipid Nanoformulations for Oral Delivery of Bioactives: An Overview
Current Drug Therapy Discovery of Biomarkers in Hepatocellular Carcinoma Metastasis Using Bioinformatic Analysis
Current Bioinformatics Synthesis and Activity of N-Sulfonylamides of Tripeptides as Potential Urokinase Inhibitors
Protein & Peptide Letters Unequivocal Role of Pyrazine Ring in Medicinally Important Compounds: A Review
Mini-Reviews in Medicinal Chemistry EGFR-Targeted Therapy in Malignant Glioma: Novel Aspects and Mechanisms of Drug Resistance
Current Molecular Pharmacology Mitochondria-Mediated Oxidative Stress: Old Target for New Drugs
Current Medicinal Chemistry New Improved Drug Delivery Technologies for Pentacyclic Triterpenes: A Review
Protein & Peptide Letters A Review of the Recent Developments in Synthetic Anti-Breast Cancer Agents
Anti-Cancer Agents in Medicinal Chemistry STING Activation and its Application in Immuno-Oncology
Current Topics in Medicinal Chemistry Extra Virgin Olive Oils Polyphenols: Biological Activities
Current Pharmaceutical Design An Integrative “Omics” Approach, for Identification of Bona Fides PLK1 Associated Biomarker in Esophageal Adenocarcinoma
Current Cancer Drug Targets γ-Tocotrienol Induces Apoptosis in Human T Cell Lymphoma through Activation of Both Intrinsic and Extrinsic Pathways
Current Pharmaceutical Design Discovery of a Highly Potent and Novel Gambogic Acid Derivative as an Anticancer Drug Candidate
Anti-Cancer Agents in Medicinal Chemistry