CHEMICAL ANALYSIS OF ANTIBIOTIC RESIDUES IN FOOD -- CONTENTS -- Preface -- Acknowledgment -- Editors -- Contributors -- 1 Antibiotics: Groups and Properties -- 1.1 Introduction -- 1.1.1 Identification -- 1.1.2 Chemical Structure -- 1.1.3 Molecular Formula -- 1.1.4 Composition of the Substance -- 1.1.5 pKa -- 1.1.6 UV Absorbance -- 1.1.7 Solubility -- 1.1.8 Stability -- 1.2 Antibiotic Groups and Properties -- 1.2.1 Terminology -- 1.2.2 Fundamental Concepts -- 1.2.3 Pharmacokinetics of Antimicrobial Drugs -- 1.2.4 Pharmacodynamics of Antimicrobial Drugs -- 1.2.4.1 Spectrum of Activity -- 1.2.4.2 Bactericidal and Bacteriostatic Activity -- 1.2.4.3 Type of Killing Action -- 1.2.4.4 Minimum Inhibitory Concentration and Minimum Bactericidal Concentration -- 1.2.4.5 Mechanisms of Action -- 1.2.5 Antimicrobial Drug Combinations -- 1.2.6 Clinical Toxicities -- 1.2.7 Dosage Forms -- 1.2.8 Occupational Health and Safety Issues -- 1.2.9 Environmental Issues -- 1.3 Major Groups of Antibiotics -- 1.3.1 Aminoglycosides -- 1.3.2 b-Lactams -- 1.3.3 Quinoxalines -- 1.3.4 Lincosamides -- 1.3.5 Macrolides and Pleuromutilins -- 1.3.6 Nitrofurans -- 1.3.7 Nitroimidazoles -- 1.3.8 Phenicols -- 1.3.9 Polyether Antibiotics (Ionophores) -- 1.3.10 Polypeptides, Glycopeptides, and Streptogramins -- 1.3.11 Phosphoglycolipids -- 1.3.12 Quinolones -- 1.3.13 Sulfonamides -- 1.3.14 Tetracyclines -- 1.4 Restricted and Prohibited Uses of Antimicrobial Agents in Food Animals -- 1.5 Conclusions -- Acknowledgments -- References -- 2 Pharmacokinetics, Distribution, Bioavailability, and Relationship to Antibiotic Residues -- 2.1 Introduction -- 2.2 Principles of Pharmacokinetics -- 2.2.1 Pharmacokinetic Parameters -- 2.2.2 Regulatory Guidelines on Dosage Selection for Efficacy -- 2.2.3 Residue Concentrations in Relation to Administered Dose.

2.2.4 Dosage and Residue Concentrations in Relation to Target Clinical Populations -- 2.2.5 Single-Animal versus Herd Treatment and Establishment of Withholding Time (WhT) -- 2.2.6 Influence of Antimicrobial Drug (AMD) Physicochemical Properties on Residues and WhT -- 2.3 Administration, Distribution, and Metabolism of Drug Classes -- 2.3.1 Aminoglycosides and Aminocyclitols -- 2.3.2 b-Lactams: Penicillins and Cephalosporins -- 2.3.3 Quinoxalines: Carbadox and Olaquindox -- 2.3.4 Lincosamides and Pleuromutilins -- 2.3.5 Macrolides, Triamilides, and Azalides -- 2.3.6 Nitrofurans -- 2.3.7 Nitroimidazoles -- 2.3.8 Phenicols -- 2.3.9 Polyether Antibiotic Ionophores -- 2.3.10 Polypeptides -- 2.3.11 Quinolones -- 2.3.12 Sulfonamides and Diaminopyrimidines -- 2.3.13 Polymyxins -- 2.3.14 Tetracyclines -- 2.4 Setting Guidelines for Residues by Regulatory Authorities -- 2.5 Definition, Assessment, Characterization, Management, and Communication of Risk -- 2.5.1 Introduction and Summary of Regulatory Requirements -- 2.5.2 Risk Assessment -- 2.5.2.1 Hazard Assessment -- 2.5.2.2 Exposure Assessment -- 2.5.3 Risk Characterization -- 2.5.4 Risk Management -- 2.5.4.1 Withholding Times -- 2.5.4.2 Prediction of Withdholding Times from Plasma Pharmacokinetic Data -- 2.5.4.3 International Trade -- 2.5.5 Risk Communication -- 2.6 Residue Violations: Their Significance and Prevention -- 2.6.1 Roles of Regulatory and Non-regulatory Bodies -- 2.6.2 Residue Detection Programs -- 2.6.2.1 Monitoring Program -- 2.6.2.2 Enforcement Programs -- 2.6.2.3 Surveillance Programs -- 2.6.2.4 Exploratory Programs -- 2.6.2.5 Imported Food Animal Products -- 2.6.2.6 Residue Testing in Milk -- 2.7 Further Considerations -- 2.7.1 Injection Site Residues and Flip-Flop Pharmacokinetics -- 2.7.2 Bioequivalence and Residue Depletion Profiles -- 2.7.3 Sales and Usage Data.

2.7.3.1 Sales of AMDs in the United Kingdom, 2003-2008 -- 2.7.3.2 Comparison of AMD Usage in Human and Veterinary Medicine in France, 1999-2005 -- 2.7.3.3 Global Animal Health Sales and Sales of AMDs for Bovine Respiratory Disease -- References -- 3 Antibiotic Residues in Food and Drinking Water, and Food Safety Regulations -- 3.1 Introduction -- 3.2 Residues in Food-Where is the Smoking Gun? -- 3.3 How Allowable Residue Concentrations Are Determined -- 3.3.1 Toxicology-Setting Concentrations Allowed in the Human Diet -- 3.3.2 Setting Residue Concentrations for Substances Not Allowed in Food -- 3.3.3 Setting Residue Concentrations Allowed in Food -- 3.3.3.1 Tolerances -- 3.3.3.2 Maximum Residue Limits -- 3.3.4 International Harmonization -- 3.4 Indirect Consumer Exposure to Antibiotics in the Natural Environment -- 3.4.1 Transport to and Occurrence in Surface Waters and Groundwaters -- 3.4.2 Uptake of Antibiotics into Crops -- 3.4.3 Risks of Antibiotics in the Environment to Human Health -- 3.5 Summary -- References -- 4 Sample Preparation: Extraction and Clean-up -- 4.1 Introduction -- 4.2 Sample Selection and Pre-treatment -- 4.3 Sample Extraction -- 4.3.1 Target Marker Residue -- 4.3.2 Stability of Biological Samples -- 4.4 Extraction Techniques -- 4.4.1 Liquid-Liquid Extraction -- 4.4.2 Dilute and Shoot -- 4.4.3 Liquid-Liquid Based Extraction Procedures -- 4.4.3.1 QuEChERS -- 4.4.3.2 Bipolarity Extraction -- 4.4.4 Pressurized Liquid Extraction (Including Supercritical Fluid Extraction) -- 4.4.5 Solid Phase Extraction (SPE) -- 4.4.5.1 Conventional SPE -- 4.4.5.2 Automated SPE -- 4.4.6 Solid Phase Extraction-Based Techniques -- 4.4.6.1 Dispersive SPE -- 4.4.6.2 Matrix Solid Phase Dispersion -- 4.4.6.3 Solid Phase Micro-extraction -- 4.4.6.4 Micro-extraction by Packed Sorbent -- 4.4.6.5 Stir-bar Sorptive Extraction.

4.4.6.6 Restricted-Access Materials -- 4.4.7 Solid Phase Extraction-Based Selective Approaches -- 4.4.7.1 Immunoaffinity Chromatography -- 4.4.7.2 Molecularly Imprinted Polymers -- 4.4.7.3 Aptamers -- 4.4.8 Turbulent-Flow Chromatography -- 4.4.9 Miscellaneous -- 4.4.9.1 Ultrafiltration -- 4.4.9.2 Microwave-Assisted Extraction -- 4.4.9.3 Ultrasound-Assisted Extraction -- 4.5 Final Remarks and Conclusions -- References -- 5 Bioanalytical Screening Methods -- 5.1 Introduction -- 5.2 Microbial Inhibition Assays -- 5.2.1 The History and Basic Principles of Microbial Inhibition Assays -- 5.2.2 The Four-Plate Test and the New Dutch Kidney Test -- 5.2.3 Commercial Microbial Inhibition Assays for Milk -- 5.2.4 Commercial Microbial Inhibition Assays for Meat-, Egg-, and Honey-Based Foods -- 5.2.5 Further Developments of Microbial Inhibition Assays and Future Prospects -- 5.2.5.1 Sensitivity -- 5.2.5.2 Test Duration -- 5.2.5.3 Ease of Use -- 5.2.5.4 Automation -- 5.2.5.5 Pre-treatment of Samples -- 5.2.5.6 Confirmation/Class-Specific Identification -- 5.2.6 Conclusions Regarding Microbial Inhibition Assays -- 5.3 Rapid Test Kits -- 5.3.1 Basic Principles of Immunoassay Format Rapid Tests -- 5.3.2 Lateral-Flow Immunoassays -- 5.3.2.1 Sandwich Format -- 5.3.2.2 Competitive Format -- 5.3.3 Commercial Lateral-Flow Immunoassays for Milk, Animal Tissues, and Honey -- 5.3.4 Receptor-Based Radioimmunoassay: Charm II System -- 5.3.5 Basic Principles of Enzymatic Tests -- 5.3.5.1 The Penzyme Milk Test -- 5.3.5.2 The Delvo-X-PRESS -- 5.3.6 Conclusions Regarding Rapid Test Kits -- 5.4 Surface Plasmon Resonance (SPR) Biosensor Technology -- 5.4.1 Basic Principles of SPR Biosensor -- 5.4.2 Commercially Available SPR Biosensor Applications for Milk, Animal Tissues, Feed, and Honey -- 5.4.3 Conclusions Regarding Surface Plasmon Resonance (SPR) Technology.

5.5 Enzyme-Linked Immunosorbent Assay (ELISA) -- 5.5.1 Basic Principles of ELISA -- 5.5.2 Automated ELISA Systems -- 5.5.3 Alternative Immunoassay Formats -- 5.5.4 Commercially Available ELISA Kits for Antibiotic Residues -- 5.5.5 Conclusions Regarding ELISA -- 5.6 General Considerations Concerning the Performance Criteria for Screening Assays -- 5.7 Overall Conclusions on Bioanalytical Screening Assays -- Abbreviations -- References -- 6 Chemical Analysis: Quantitative and Confirmatory Methods -- 6.1 Introduction -- 6.2 Single-Class and Multi-class Methods -- 6.3 Chromatographic Separation -- 6.3.1 Chromatographic Parameters -- 6.3.2 Mobile Phase -- 6.3.3 Conventional Liquid Chromatography -- 6.3.3.1 Reversed Phase Chromatography -- 6.3.3.2 Ion-Pairing Chromatography -- 6.3.3.3 Hydrophilic Interaction Liquid Chromatography -- 6.3.4 Ultra-High-Performance or Ultra-High-Pressure Liquid Chromatography -- 6.4 Mass Spectrometry -- 6.4.1 Ionization and Interfaces -- 6.4.2 Matrix Effects -- 6.4.3 Mass Spectrometers -- 6.4.3.1 Single Quadrupole -- 6.4.3.2 Triple Quadrupole -- 6.4.3.3 Quadrupole Ion Trap -- 6.4.3.4 Linear Ion Trap -- 6.4.3.5 Time-of-Flight -- 6.4.3.6 Orbitrap -- 6.4.4 Other Advanced Mass Spectrometric Techniques -- 6.4.4.1 Ion Mobility Spectrometry -- 6.4.4.2 Ambient Mass Spectrometry -- 6.4.4.3 Other Recently Developed Desorption Ionization Techniques -- 6.4.5 Fragmentation -- 6.4.6 Mass Spectral Library -- Acknowledgment -- Abbreviations -- References -- 7 Single-Residue Quantitative and Confirmatory Methods -- 7.1 Introduction -- 7.2 Carbadox and Olaquindox -- 7.2.1 Background -- 7.2.2 Analysis -- 7.2.3 Conclusions -- 7.3 Ceftiofur and Desfuroylceftiofur -- 7.3.1 Background -- 7.3.2 Analysis Using Deconjugation -- 7.3.3 Analysis of Individual Metabolites -- 7.3.4 Analysis after Alkaline Hydrolysis -- 7.3.5 Conclusions.

7.4 Chloramphenicol.