Handbook of Analysis of Oligonucleotides and Related Products / Edition 1

by Jose V. Bonilla, G. Susan Srivatsa

Overview

Oligonucleotides represent one of the most significant pharmaceutical breakthroughs in recent years, showing great promise as diagnostic and therapeutic agents for malignant tumors, cardiovascular disease, diabetes, viral infections, and many other degenerative disorders. The Handbook of Analysis of Oligonucleotides and Related Products is an essential reference manual on the practical application of modern and emerging analytical techniques for the analysis of this unique class of compounds. A strong collaboration among thirty leading analytical scientists from around the world, the book provides readers with a comprehensive overview of the most commonly used analytical techniques and their advantages and limitations in assuring the identity, purity, quality, and strength of an oligonucleotide intended for therapeutic use.

Topics discussed include:

• Strategies for enzymatic or chemical degradation of chemically modified oligonucleotides toward mass spectrometric sequencing
• Purity analysis by chromatographic or electrophoretic methods, including RP-HPLC, AX-HPLC, HILIC, SEC, and CGE
• Characterization of sequence-related impurities in oligonucleotides by mass spectrometry and chromatography
• Structure elucidation by spectroscopic methods (IR, NMR, MS) as well as base composition and thermal melt analysis (T_m)
• Approaches for the accurate determination of molar extinction coefficient of oligonucleotides
• Accurate determination of assay values
• Assessment of the overall quality of oligonucleotides, including microbial analysis and determination of residual solvents and heavy metals
• Strategies for determining the chemical stability of oligonucleotides
• The use of hybridization techniques for supporting pharmacokinetics and drug metabolism studies in preclinical and clinical development
• Guidance for the presentation of relevant analytical information towards meeting current regulatory expectations for oligonucleotide therapeutics

This resource provides a practical guide for applying state-of-the-art analytical techniques in research, development, and manufacturing settings.

Product Details

ISBN-13:	9781138198456
Publisher:	Taylor & Francis
Publication date:	10/19/2016
Pages:	512
Product dimensions:	6.88(w) x 9.69(h) x (d)

About the Author

Dr. Jose V. Bonilla’s career has been dedicated to the introduction and implementation of cutting-edge analytical technologies such as LC-MS, high-speed gas chromatography, high-speed GPC, online GC, online HPLC, and online near-IR. He has extensive experience in the management of industrial and pharmaceutical analytical laboratories in compliance with regulatory requirements and is the author and coauthor of several peer-reviewed publications.

Dr. G. Susan Srivatsa has more than 20 years of experience in the development of small molecules, proteins, peptides, and oligonucleotides as therapeutics. She has contributed to the successful development of more than 35 DNA and RNA oligonucleotide drug candidates through various stages of clinical development and has published widely in the area of oligonucleotide analysis in peer-reviewed journals.

Table of Contents

Purity Analysis and Impurities Determination by Reversed-Phase High- Performance Liquid Chromatography. Purity Analysis and Impurities Determination by AEX-HPLC. Purity Analysis and Molecular Weight Determination by Size Exclusion HPLC Analysis. Analysis of Oligonucleotides by Liquid Chromatography—Mass Spectrometry. Sequence Determination and Confirmation by MS/M S and MALDI-TOF. Tm Analysis of Oligonucleotides. Purity and Content Analysis of Oligonucleotides by Capillary Gel Electrophoresis. Bioanalysis of Therapeutic Oligonucleotides Using Hybridization-Based Immunoassay Techniques. Oligonucleotide Assay and Potency. Microbial Analysis: Endotoxin Testing. Analysis of Residual Solvents by Head Space Gas Chromatography. Determination of Extinction Coefficient. Structural Determination by NMR. Infrared Analysis of Oligonucleotides. Stability Indicating Methods for Oligonucleotide Products. Analysis by Hydrophilic Interaction Chromatography. Determination of Base Composition. Analysis of Metals in Oligonucleotides. Regulatory Considerations for the Development of Oligonucleotide Therapeutics.

Editorial Reviews

This is a unique resource for guiding the analysis of oligonucleotide-based drug products. No other single source provides such a comprehensive overview of the necessary analytical techniques that assess the qualitative characteristics of oligonucleotides intended for pharmaceutical use.
—Rachel R Chennault, Ph.D.(American College of Clinical Pharmacy), in Doody's Notes

From the Publisher

Reviewer: Rachel R Chennault, PhD (American College of Clinical Pharmacy)
Description: This is an essential overview of the modern analytical techniques that are most commonly used in assessing characteristics of oligonucleotides, such as structure, purity, and quality, developed for therapeutic use.
Purpose: The use of oligonucleotides as powerful diagnostic and therapeutic agents has important applications in managing a variety of human disease states and conditions. In this book, the authors describe the range of necessary analytical methodologies for determining oligonucleotide properties during the drug research, development, and manufacturing processes.
Audience: There are several important, yet technically challenging, characterization steps in developing oligonucleotide-based drugs. As such, the chapters of this book receive input from leading scientific experts with vast experience in the innovative methods that guide the oligonucleotide-based drug development process. This is a highly technical reference manual that will serve as a practical resource for readers in oligonucleotide drug research, development, and manufacturing settings.
Features: It addresses the steps of oligonucleotide characterization in separate chapters, each highlighting the suitability of individual state-of-the-art methodologies to the relevant step, in addition to challenges and limitations. As there are currently no formal regulations for this class of drugs and only two oligonucleotide drugs have been approved for therapeutic use in the United States, the chapter dedicated to regulatory considerations is particularly useful in providing chemistry, manufacturing, and quality control expectations that may guide the investigational new drug application process for compounds in this class.
Assessment: This is a unique resource for guiding the analysis of oligonucleotide-based drug products. No other single source provides such a comprehensive overview of the necessary analytical techniques that assess the qualitative characteristics of oligonucleotides intended for pharmaceutical use.

Doody's Review Service