Handbook of Analytical Quality by Design addresses the steps involved in analytical method development and validation in an effort to avoid quality crises in later stages. The AQbD approach significantly enhances method performance and robustness which are crucial during inter-laboratory studies and also affect the analytical lifecycle of the developed method. Sections cover sample preparation problems and the usefulness of the QbD concept involving Quality Risk Management (QRM), Design of Experiments (DoE) and Multivariate (MVT) Statistical Approaches to solve by optimizing the developed method, along with validation for different techniques like HPLC, UPLC, UFLC, LC-MS and electrophoresis. This will be an ideal resource for graduate students and professionals working in the pharmaceutical industry, analytical chemistry, regulatory agencies, and those in related academic fields.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This book brings together most up-to-date information on different aspects of brain aging and on the strategies for intervention and therapy of age-related brain disorders. It includes 18 chapters by leading researchers, and each chapter is a comprehensive and critical review of the topic in question, discusses the current scenario and focuses on future perspectives. The target readership is the undergraduate and graduate students in the universities, in medical and nursing colleges, along with the post-graduate researchers and practicing clinicians who would like to know about the latest developments in the field of neurodegenerative disorders and their therapeutic interventions. This book will be of much interest to pharmaceutical, nutrition and healthcare industry for an easy access to accurate and reliable information in the field of aging research and intervention.

Drug-related problems in the elderly is intended to serve as a source of information and clinical support in geriatric pharmacotherapy for students as well as all health care professionals, e.g. physicians, nurses and pharmacists. Pharmacotherapy is of great importance to all mankind. Drugs are however powerful and must be handled appropriately. This is especially important for elderly patients. Drug-related problem is not a major subject in most university programmes in medicine or pharmacy. When there is no speci c course, there is often no book covering the topic. In our view, as teachers at various university courses, there has been a shortage of literature that re ects the most important aspects of drug-related problems in the elderly. Medical practitioners, nurses and pharmacists, need to have this knowledge to be able to serve their patients in the best way. This book covers most aspects of drug-related problems in the elderly. With b- ter knowledge of drug-related dif culties and risks we hope that elderly will have fewer drug-related problems and bene t more from their pharmacotherapy.

Endocannabinoids have tremendous therapeutic potential. This book introduces readers to our current understanding of the neurobiology of endocannabinoids and related systems, detailing their pathophysiological role and therapeutic potential. Authors, experienced clinical investigators, present and analyze results of recent clinical trials as well as the development of new therapeutic strategies and medicines.

The fact that tobacco ingestion can affect how people feel and think has been known for millennia, placing the plant among those used spiritually, honori?cally, and habitually (Corti 1931; Wilbert 1987). However, the conclusion that nicotine - counted for many of these psychopharmacological effects did not emerge until the nineteenth century (Langley 1905). This was elegantly described by Lewin in 1931 as follows: "The decisive factor in the effects of tobacco, desired or undesired, is nicotine. . . "(Lewin 1998). The use of nicotine as a pharmacological probe to und- stand physiological functioning at the dawn of the twentieth century was a landmark in the birth of modern neuropharmacology (Limbird 2004; Halliwell 2007), and led the pioneering researcher John Langley to conclude that there must exist some "- ceptive substance" to explain the diverse actions of various substances, including nicotine, when applied to muscle tissue (Langley 1905). Research on tobacco and nicotine progressed throughout the twentieth century, but much of this was from a general pharmacological and toxicological rather than a psychopharmacological perspective (Larson et al. 1961). There was some attention to the effects related to addiction, such as euphoria (Johnston 1941), tolerance (Lewin 1931), and withdrawal (Finnegan et al. 1945), but outside of research supported by the tobacco industry, addiction and psychopharmacology were not major foci for research (Slade et al. 1995; Hurt and Robertson 1998; Henning?eld et al. 2006; Henning?eld and Hartel 1999; Larson et al. 1961).

Protein kinase C (PKC), a family of serine-threonine kinases, rocketed to the forefront of the cancer research field in the early 1980's with its identification as an effector of phorbol esters, natural products with tumor promoting activity. Phorbol esters had long been of interest to the cancer research field due to early studies in the mouse skin carcinogenesis model, which showed that prolonged topical application of phorbol esters promoted the formation of skin tumors on mice previously treated with mutagenic agents. Research in the last years has established key roles for PKC isozymes in the control of cell proliferation, migration, adhesion, and malignant transformation. In addition, there is a large body of evidence linking PKC to invasion and cancer cell metastasis. Moreover, it is now well established that the expression of PKC isozymes is altered in various types of cancers. More importantly, small molecule inhibitors have been developed with significant anti-cancer activity. The relevance of PKC isozymes in cancer signaling is therefore remarkable. This book will have 4 sections. There will be 23 chapters. Each section will have a brief introduction by an expert in the field (~ 1-2 pages).

A major challenge confronting the pharmaceutical scientist working with protein formulation is the instability during processing, storage and use of the protein drug. This book reviews stability aspects encountered since the pioneering isolation of insulin in 1921. An introductory chapter, treating insulin purity and stability in historical perspective, is followed by a chapter with a description of the structure of insulin. The main part of the book is a comprehensive review of the literature dealing with stability of insulin in pharmaceutical formulation, including biological stability and the physical and chemical decomposition of insulin. The physical stability (i.e. the tendency of insulin to form insoluble fibrils) is reviewed as are methods to stabilize insulin for long-term use in infusion pumps. The book will be of interest to research and clinical pharmacologists involved with insulin and other protein-based drug substances.

Sildenafil, for the treatment of erectile dysfunction, is one of the first products that has made its way successfully from basic NO (nitrous oxide) research, to clinical routine therapy. Sidenafil, part of the Milestones in Drug Therapy series, presents the major breakthroughs in the field of NO physiology and pharmacology that led to the development of the drug, as well as clinical applications in one source guide.

Written by leading experts in the field, each chapter covers aspects of clinical use and experience, pharmacokinetics, pharmacodynamics, biochemistry, and cultural science.

The idea for this book came from discussions among participants in a symposium on biotechnical applications at the "Pacifichem 89" meeting in Honolulu. It was the majority opinion of this group that a volume dedicated to biotechnical and biomedical applications of PEG chemistry would enhance research and development in this area. Though the book was conceived at the Honolulu meeting, it is not a proceedings of this symposium. Several groups who did not participate in this meeting are repre sented in the book, and the book incorporates much work done after the meeting. The book does not include contributions in all related areas to which PEG chemistry has been applied. Several invited researchers declined to parti.: ipate, and there is not enough space in this single volume to properly cover all submissions. Chapter I-an overview of the topic-discusses in brief applications not given detailed coverage in specifically devoted chapters. The following topics are covered: introduction to and fundamental properties of PEG and derivatives in Chapters 1-3; separations using aqueous polymer two-phase partitioning in Chapters 4-6; PEG-proteins as catalysts in biotechnical applications in Chapters 7 and 8; biomedical applications of PEG-proteins in Chapters 9-13; PEG modified surfaces for a variety of biomedical and biotechnical applications in Chapters 14-20; and synthesis of new PEG derivatives in Chapters 21 and 22."

This book provides a comprehensive overview of chitin biology and chitin metabolism related enzymes. Chitin, the second most abundant biopolymer in nature after to cellulose, is a linear biopolymer composed of -1,4-linked N-acetylglucosamine (GlcNAc), and an essential component in the exoskeletons of insects, mites, ticks and crustaceans, the egg shells of parasitic nematodes, and fungal cell walls. Although some chitin-containing organisms are a threat to human health, food safety and agricultural production, non-chitin containing organisms like humans, mammals and plants have an innate immune response to these hazardous organisms. The book provides researchers and students with information on the recent research advances concerning the biology of chitin-containing organisms as well as cross-talks between chitin-containing and non-chitin-containing organisms. Highlighting chitin remodeling enzymes and inhibitors, it also offers drug developers essential insights into designing specific molecules for the control of hazardous chitin-containing organisms.

In this book, leading-edge investigators offer effective strategies to improve current antidepressive therapies and suggest molecular, biological, and genetic approaches that will lead to the development of novel antidepressants. The contributors' critical reviews and commentaries illuminate our understanding of the mechanism(s) responsible for antidepressant action. The book's goal is to move beyond current biogenic amine-based concepts and therapies to the development of new and improved antidepressants that are more effective and have a more rapid onset than current.

Understanding an individual's genetic makeup is the key to creating personalized drugs with greater efficacy and safety, and pharmacogenomics aims to study the complex genetic basis of inter-patient variability in response to drug therapy. Based upon the success of its first edition, the second edition of Pharmacogenomics: Methods And Protocols aims to continue providing readers with high-quality content on the most innovative and commonly adopted technologies in the field of pharmacogenomics as presented by experts in the field. Broken into several sections, this detailed volume examines techniques for interrogating variation in human genes and genomes, functional assessment of genetic variation, both in vitro and in vivo, as well as tools for translation and implementation of pharmacogenetic markers. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to the respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Comprehensive and thoroughly updated, Pharmacogenomics: Methods And Protocols, Second Edition serves as an essential reference and an invaluable source on the latest information in this field.

This volume - like the NATO Advanced Research Workshop on which it is based - addresses the fundamental science that contributes to our understanding of the potential risks from ecological terrorism, i.e. dirty bombs, atomic explosions, intentional release of radionuclides into water or air. Both effects on human health (DNA and systemic effects) and on ecosystems are detailed, with particular focus on environmentally relevant low-dose ranges. The state-of-the-art contributions to the book are authored by leading experts; they tackle the relevant questions from the perspectives of radiation genetics, radiobiology, radioecology, radiation epidemiology and risk assessment.

Since the subject of high dilution effects is still a subject for debate, this volume provides evidence in support of effects from control clinical studies, clinical records from veteran physicians, controlled experiments on animals and plants, and in vitro tests without any organisms (Chapter II). An overview of the methods for preparing drugs at ultra high dilution is also provided as well as the basic principles of homeopathy, which has been alleviating human suffering through the use of these drugs for several hundred years (Chapter I). Chapter III provides physical basis of high dilutions as evidence from the NMR, IR, UV and fluorescence spectra of those drugs. Since water is used as the diluents media, the structure and dynamics of water polymers in relation to high dilution are discussed in order to facilitate easy comprehension of this physical aspect, the basic principles of spectroscopy are also described. Chapter IV focuses on the mechanism of action of potentized drugs in the living system, discussing the structure of the cell, the plasma membrane, the integral proteins on the membrane, the interaction between these proteins and high dilutions and the manifestations of the therapeutic effects of high dilutions. Some aspects, peculiar to homeopathy, such as the chief miasm psora, and the literalities and time modalities of symptoms and drug action are interpreted from a scientific perspective. Chapter IV ends with a brief discussion on water structures and the origin of life to show the natural evolution of high dilution effects. The book not only helps in understanding the physical basis of high dilutions and their mechanism of action in organisms but provides many new avenues of investigation into this interdisciplinary field of science.

This book, with its 16 chapters, documents the present state of knowledge of the adenosine A receptor. It covers a wide range of information, including data from 3 studies of theoretical, molecular and cellular pharmacology, signal transduction, integrative physiology, new drug discoveries and clinical applications. It fills an important gap in the literature since no alternative source of such information is currently available. Although the A receptor is increasingly being recognized for 3 its increasing number of biological roles throughout the body and many A receptor 3 ligands have proven useful in elucidating peripheral and central pathologies, many issues remain unresolved. Moreover, research activity in this field continues to grow exponentially, resulting in a constant flow of new information. The chapters in this book cover both basic science and the relevant applications and provide an authoritative account of the current status of the field. They have enabled my goal as editor to make "A Adenosine Receptors from Cell Biology to Pharmacology and 3 Therapeutics" an up to date, scientifically excellent, reference source, attractive to basic and clinical scientists alike, a reality. Detailed understanding of the physico-chemical aspects and molecular biology of the A receptor provides a solid basis for its future development as a target for 3 adenosine-based pharmacotherapies (Chapters 2 and 3).

Paul H. Axelsen concisely summarizes all the essential medical data concerning the leading antimicrobials used in fighting infectious diseases and clearly illustrates their mechanisms of action. The agents described range from antibacterial and antifungal to antiparasitic and antiviral agents, and include immunomodulators and immunizing agents. For each drug discussed, the book allows rapid access to the essential facts concerning its structure and mechanism of action, the spectrum of its activity, its pharmacokinetics, its adverse effects, and its resistance. This book provides medical students, physicians, and allied health professionals with rapid access to the core principles of antimicrobial pharmacology, and a foundation for decisions about the use of antimicrobials in daily practice.

Cocaine has been a socio-medical problem for centuries. In the United States, the first cocaine epidemic occurred between the 1880s and the 1920s. In the 1960s shortages of heroin as well as government programs to stop the smuggling of marijuana may have stimulated the use of cocaine as a substitute. With the development of crack, cocaine became available at a price that made it accessible to virtually anyone. Today, the long-term effects of crack are just beginning to be felt, especially among children born of users. Treatment of cocaine abuse has traditionally been non-pharmacological, although beginning with the 1980s, various drugs have been used to decrease cocaine craving. This bibliography contains more than 600 references, spanning a century of research and writing. Source publications, all of which are annotated, include books, articles, conference proceedings, dissertations, and government publications. The material is organized within four subject-oriented chapters, and alphabetically within each chapter. Author and subject indexes provide additional access. In addition, Miletich includes appendixes on common names for cocaine, videocassettes about the drug, and a timeline. The work will be of value to researchers as well as social workers, psychologists, and others working in the substance abuse field.

This book is based on the proceedings of the symposium entitled "Di rected Drug Delivery: A Multidisciplinary Problem," which was held in Lawrence, Kansas on October 17-19, 1984. The purpose of the sym posium and this book is to focus on the multidisciplinary nature of drug delivery. Development of a successful drug delivery system re quires contributions from various scientific disciplines, including pharmaceutical chemistry, analytical chemistry, medicinal chemistry, biochemistry, pharmacology, toxicology, and clinical medicine. The contents of this volume illustrate the importance of the various disci plines in identifying the problems and approaches for the develop ment of a rational and effective drug delivery system. Thus the infor mation provided herein will be of value not only to the pharmaceutical chemists who are responsible for dosage form design, but also to the pharmacokineticists, pharmacologists, and clinicians involved in bio logical evaluation of drug delivery systems. The volume should also be of interest to the analytical chemists who must provide technology to quantitcltively evaluate drug delivery. Additionally, this work will also interest the biochemists and medicinal chemists involved in drug dis covery, since the drug delivery system often plays a major role in determining the success or failure of a new drug entity. Each speaker at the symposium was requested to contribute a chapter reviewing the contribution of their major discipline to the de velopment of a successful drug delivery system."