This book is devoted to the use of mass spectrometry in quantitative measurements of amounts of target (known) chemical compounds present at trace levels in complex matrices, such as drugs and their metabolites in body fluids, pesticide residues in foodstuffs, contaminants in drinking water, etc. Such demanding measurements, defined as 1 part in 10^6 - 10^12, involve the use of a wide range of apparatus and of experimental procedures and methods of data evaluation, all of which must be utilized properly if reliable estimates of chemical concentrations and their associated uncertainties are to be obtained. While this is true of any chemical analysis, modern advances in trace-level analysis are critically dependent on developments in mass spectrometry.The approach adopted throughout the book is to emphasize the fundamentals underlying the scientific instruments and methodologies, illustrated by historically important developments and more recent innovations. However, discussions of the fundamentals are reinforced and related to the real-world by two chapters dedicated to method development and validation. Finally, how the fundamental things apply to real-world problems is illustrated in the final chapter devoted to representative examples from a wide range of application areas.This book does not cover important branches of mass spectrometry that provide accurate and precise quantitative measurements of relative concentrations, e.g. variations in isotopic ratios of an element by isotope ratio mass spectrometry and accelerator mass spectrometry. Rather, it is mainly concerned with determinations of absolute amount of substance, particularly for small organic molecules present at trace levels in complex matrices.The book* covers analysis of small (* provides a comprehensive introduction to the ancillary techniques and tools, including statistical analysis, that must be coordinated to provide a reliable result for a trace-level quantitative analysis by mass spectrometry.* discusses method development and validation, GLP, etc., in the context of a fitness-for-purpose approach that is applicable to any quantitative analytical method.* written at a level that presupposes some basic undergraduate-level knowledge of chemistry, physics, and mathematics and statistics.* treats the more recent developments in quantitative analysis of specific proteins in biological systems using proteolytic peptides as surrogate analytes.Any book such as this can only be regarded as a preparation for the real learning process in this demanding practical art, namely learning by doing i.e. working on real-life problems in a laboratory. However, this book will be useful both in providing enough background information (learning from others) that the first exposure to the learning by doing process will not seem quite so daunting, and also will provide useful background for evaluation of new technologies as they appear.