The first edition of this now classic work helped to establish mass spectrometry as the premier tool for drug metabolism studies. Completely rewritten from start to finish, Using Mass Spectrometry for Drug Metabolism Studies, Second Edition brings medicinal chemists and mass spectrometry professionals up to speed with the rapid advances in the fiel

This timely reference discusses mass spectrometry in drug metabolism and pharmacokinetic studies. With contributions by professionals from the pharmaceutical industry, this book begins with a review of current mass spectrometry techniques and applications, followed by discussions of various methods for using MS in drug metabolism studies and pharmacokinetics. Highlighting the critical importance of ADME studies for understanding how a drug is absorbed, distributed, metabolized, and excreted by the body, the book s focuses on the use of LC/MS and MALDI-MS. This is a valuable reference for scientists in the pharmaceutical industry, medicine, academia, and even those working in homeland defense.

This book examines the background, industrial context, process, analytical methodology, and technology of metabolite identification. It emphasizes the applications of metabolite identification in drug research. While primarily a textbook, the book also functions as a comprehensive reference to those in the industry. The authors have worked closely together and combine complementary backgrounds to bring technical and cultural awareness to this very important endeavor while serving to address needs within academia and industry It also contains a variety of problem sets following specific sections in the text.

The introduction of combinatorial chemistry technology has increased the amount of compounds generated in a year from 50 to 2000. Conventional analytical approaches simply cannot keep up. These circumstances have caused drug discovery to take on the shape of a bottleneck, like traffic through a toll booth. In order to break the bottleneck, a corres

Drug metabolism comprises the identification, characterization, and quantification of the chemicals or compounds produced in an animal or human upon administration of a drug. Research practices not only require the chemical structure but also aim to determine the pharmacological activities and/or toxicity of these compounds. This is first performed in animals, as studies attempt to identify and quantify metabolites, and later in humans, with care to further characterize metabolites that are either unique to or produced disproportionately in humans compared to animals. Characterization includes the determination of enzyme systems or other biological mechanisms that produce each identified metabolite; this information is used to predict potential drug-drug interactions with other compounds that increase or decrease metabolite formation and sources of biological variability in response or toxicity with varying patient genetics, which affect CYP isoform expression. This book’s purpose is to provide some understanding of the biology and current technology applied in the field of drug metabolism.

In order to avoid late-stage drug failure due to factors such as undesirable metabolic instability, toxic metabolites, drug-drug interactions, and polymorphic metabolism, an enormous amount of effort has been expended by both the pharmaceutical industry and academia towards developing more powerful techniques and screening assays to identify the metabolic profiles and enzymes involved in drug metabolism. This book presents some in-depth reviews of selected topics in drug metabolism. Among the key topics covered are: the interplay between drug transport and metabolism in oral bioavailability; the influence of genetic and epigenetic factors on drug metabolism; impact of disease on transport and metabolism; and the use of novel microdosing techniques and novel LC/MS and genomic technologies to predict the metabolic parameters and profiles of potential new drug candidates.

When a dose of drug is administered, three main phases of drug action may be distingushed. In the "pharmaceutical" phase the dosage form disintegrates, the active substance dissolves and becomes available for absorption. The second phase ("pharmaco kinetic" phase) includes absorption, distribution, metabolism, and excretion. That fraction of the dose which finally reaches the circulation after absorption will be available for biological action in the third, or "pharmacodynamic" phase when the drug reaches the target tissues and a drug-receptor interaction takes place. The objectives in studies of drug metabolism are: (a) to identify the pathways by which drugs are transformed in the body; (b) to ascertain quantitatively the importance of each pathway and intermediate; (c) to identify and quantify endogenous constituents influenced by the drug or its metabolites which may interfere with common metabolic processes. Since metabolites usually differ from their precursors by only a single chemical group, the resulting metabolic pathways generally consist of a series of closely related compounds. Mass spectrometry is uniquely suited for the analysis of drugs and metabolites for several reasons: only a minimal amount of sample preparation is needed, closely related compounds can be analyzed in a single step, structures can often be deduced directly from the mass spectra without the need for pure reference spectra, and constituents can be quantified with relative ease even when present in fractional nanogram quantity.

This first overview of mass spectrometry-based pharmaceutical analysis is the key to improved high-throughput drug screening, rational drug design and analysis of multiple ligand-target interactions. The ready reference opens with a general introduction to the use of mass spectrometry in pharmaceutical screening, followed by a detailed description of recently developed analytical systems for use in the pharmaceutical laboratory. Applications range from simple binding assays to complex screens of biological activity and systems containing multiple targets or ligands -- all highly relevant techniques in the early stages in drug discovery, from target characterization to hit and lead finding.

A constructive evaluation of the most significant developments in liquid chromatography-mass spectrometry (LC-MS) and its uses for quantitative bioanalysis and characterization for a diverse range of disciplines, Liquid Chromatography-Mass Spectrometry, Third Edition offers a well-rounded coverage of the latest technological developments and

The Place of Mass Spectrometry in Drug Metabolism Studies.- In vitro and in Vivo Studies on the Metabolism of Dibenzo [c, f]--[1,2] Diazepine.- Gas Chromatographic-Mass Spectrometric Identification of Urinary Metabolites of Propildazine in Rat.- Mass Spectrometric Characterization of Sydnocarb ® and its Major Metabolites in Rat.- Metabolism of an Aryloxy Beta Blocking Drug.- Isolation and Identification of the Chloroform Soluble Urinary Metabolites of Suloctidil in Man.- Are Stable Sulfenic Acids Possible Metabolites of Suloctidil?.- The Electron Impact Fragmentation of Products Related to N-(A.