This volume of the Handbook of Experimental Pharmacology (Concepts in Biochemical Pharmacology) will show that pharma cology has finally arrived as a true discipline in its own right, and is no longer the handmaiden of organic chemistry and physiology. Instead it is an amalgam of all the biological sciences including biochemistry, biophysical chemistry, physiology, pathology and clinical medicine. In the volumes that make up Concepts in Bio chemical Pharmacology we hope to convince Medical Schools what should now be obvious, that pharmacology is no longer that dull topic bridging the basic sciences with medicine, but is probably the most important subject in the medical curriculum. We are grateful for the advice of Dr. Byron Clark, Director of the Pharmacology-Toxicology Program at the National Institutes of Health whose support made possible much of the work described in this volume. Contents Section Four: Methods 01 Stooging the MetoholiBm 01 Drugs Subsection A. Assay 01 Drugs and Their M etoholites Chapter 22 : Basic Principles in Development of Methods for Drug Assay. B. B. BRODIE. With 2 Figures 1 1 A. Introduction . . . . . . . . . . B. Principles of Developing a Method. . . . . . 1 I. Section of Method of Assay . . . . . . 1 II. Choice of Solvent for Extraction of Drug 2 III. Adsorption of Drugs by Glass Surfaces . . . . . . . . . . . . . . 3 IV. Recoveries of Known Amounts of Compound from Biological Material. 4 V. Assessment of Sensitivity 5 VI. Assessment of Specificity 5 References. . . . . . . . . . .

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Section Four: Methods of Studying the Metabolism of Drugs.- Subsection A. Assay of Drugs and Their Metabolites.- 22: Basic Principles in Development of Methods for Drug Assay. With 2 Figures.- 23: Absorption Spectrophotometry.- 24: Fluorometry. With 1 Figure.- 25: Radioactive Techniques: The Use of Labeled Drugs. With 2 Figures.- 26: Radioactive Techniques: Radioactive Isotope Derivatives of Nonlabeled Drugs.- 27: Gas Chromatography. With 18 Figures.- 28: Enzymatic Assays in Pharmacology. With 4 Figures.- 29: Bioassay. With 2 Figures.- 30: Immunoassay. With 2 Figures.- Subsection B. Isolation and Identification of Drug Metabolites.- 31: Paper, Column and Thin Layer Chromatography, Counter-Current Distribution and Electrophoresis..- 32: Isotope Dilution Analysis. With 4 Figures.- 33: Gas Chromatography-Mass Spectrometry. With 8 Figures.- 34: The Application of Various Spectroscopies to the Identification of Drug Metabolites. With 5 Figures.- Section Five: Sites of Drug Metabolism.- 35: Introduction: Pathways of Drug Metabolism.- Subsection A: Microsomal Enzymes.- 36: Some Morphological Characteristics of Hepatocyte Endoplasmic Reticulum and Some Relationships between Endoplasmic Reticulum, Microsomes, and Drug Metabolism.- 37: Model Systems in Studies of the Chemistry and the Enzymatic Activation of Oxygen. With 9 Figures.- 38: Cytochrome P-450 Its Function in the Oxidative Metabolism of Drugs. With 23 Figures.- 39: Enzymatic Oxidation at Carbon.- 40: N-Oxidation Enzymes. With 2 Figures.- 41: Enzymatic N-, 0-, and S-Dealkylation of Foreign Compounds by Hepatic Microsomes. With 4 Figures.- 42: Reductive Enzymes. With 6 Figures.- 43: Oxidative Desulfuration and Dearylation of Selected Organophosphate Insecticides.- 44: Metabolism of Halogenated Compounds. With 7Figures.- 45: Glucuronide-Forming Enzymes. With 1 Figure.- 46: Metabolism of Normal Body Constituents by Drug-Metabolizing Enzymes in Liver Microsomes.- 47: Tissue Distribution Studies of Polycyclic Hydrocarbon Hydroxylase Activity.- 48: Mechanisms of Induction of Drug Metabolism Enzymes. With 9 Figures.- 49: Inhibition of Drug Metabolism. With 1 Figure.- Subsection B: Nonmicrosomal Enzymes.- 50: Esterases of Human Tissues. With 2 Figures.- 51: Enzymatic Oxidation and Reduction of Alcohols, Aldehydes and Ketones.- 52: Amine Oxidases.- 53: Sulphate Conjugation Enzymes. With 3 Figures.- 54: Acetylating, Deacetylating and Amino Acid Conjugating Enzymes. With 3 Figures.- 55: Mercapturic Acid Conjugation. With 1 Figure.- 56: Methyltransferase Enzymes in the Metabolism of Physiologically Active Compounds and Drugs.- 57: Enzymes that Inactivate Vasoactive Peptides. With 2 Figures.- 58: The Metabolism of Analogs of Endogenous Substrates: Wider Application of a Limited Concept. With 15 Figures.- Author Index.