Doping in Sports (eBook)

152640_1_En_1_Chapter_OnlinePDF 12
Chapter : History of Doping and Doping Control 12
The Expression ``Doping´´ 12
Early Attempts of Doping 13
Doping and its Emerging Prohibition 13
Stimulants 16
Anabolic Agents 16
Fatalities with Presumptive Correlation to Doping 18
Development of General Anti-Doping Regulations 18
Doping Analysis and Accreditation of Anti-Doping Laboratories 20
Doping and the Cold War 22
Developments from the 1990s Onward 23
Appendix 1 Historical Definitions of Doping 26
References 29
152640_1_En_2_Chapter_OnlinePDF 35
152640_1_En_3_Chapter_OnlinePDF 75
Chapter : Phase-II Metabolism of Androgens and Its Relevance for Doping Control Analysis 75
Phase-II Metabolism of Androgens 76
Glucuronide Conjugation 76
Sulphonation 79
Genetic Polymorphism 80
Relevance of Phase-II Metabolism in Doping Control Analysis 81
In Vitro Production of Phase-II Metabolites 81
References 83
152640_1_En_4_Chapter_OnlinePDF 86
Chapter : Detecting the Administration of Endogenous Anabolic Androgenic SteroidsAnabolic Androgenic SteroidsEndogenous 86
Introduction 87
Testosterone 87
Historical Background 88
General Approach to the Measurement of Urinary Steroids 89
From Immunoassays to Mass Spectrometry 89
Sample Preparation for GC/MS Analyses 90
Stability of Urinary Steroid Conjugates 90
Testosterone and Epitestosterone 91
Reference Ranges 91
Stability of Individual Parameters 93
Alteration of the Urinary Steroid Profile 93
Testosterone 93
Dihydrotestosterone, Androstenedione and Dehydroepiandrosterone 95
Measurement of the delta13C Values of Urinary Steroid Metabolites 97
Principle of the GC/C/IRMS Analysis 97
IRMS for Determining the Origin of Organic Compounds 98
delta13C Values of Urinary Steroid Metabolites 98
External Factors Influencing the GC/MS Steroid Profile 99
Anabolic Agents and Inhibitors of Reductase 99
Ethanol 100
Supplements 101
From Population-Based to Subject-Based Testing Approach 101
References 102
152640_1_En_5_Chapter_OnlinePDF 108
Chapter : Synthetic Anabolic Agents: Steroids and Nonsteroidal Selective Androgen Receptor Modulators 108
Introduction 109
Pharmacological Aspects and Mode of Action of AAS 110
Mode of Action of AAS 111
Metabolism of AAS 111
Methyltestosterone and Metandienone 113
Stanozolol 117
Undesirable Effects of AAS 117
Cardiovascular Issues 117
Endocrine Issues 118
Hepatic Issues 118
Psychiatric Issues 118
Musculoskeletal Issues 119
Pharmacological Aspects and Mode of Action of SARMs 119
Metabolism of SARMs 120
Clinical Applications 121
Undesirable Effects of SARMs 121
Detection Strategies for AAS and SARMs 123
Sample Preparation and Analysis of AAS 123
GC-MS Analyses 124
LC-MS(/MS) Analyses 126
Sample Preparation and Analysis of SARMs 126
Conclusions 129
References 129
152640_1_En_6_Chapter_OnlinePDF 136
152640_1_En_7_Chapter_OnlinePDF 164
Chapter : Designer Steroids 164
Introduction 165
Exogenous SteroidsSteroidsExogenous 165
Endogenous SteroidsSteroidsEndogenous 166
BALCO, an Insight into Conspiracy 167
Anabolic Steroid Chemistry 169
Detection Methods 178
Use of Gas Chromatography-Mass Spectrometry (GC-MS) 180
Use of LC-MS(/MS) 183
The Supplement Market 187
Conclusion 191
References 192
152640_1_En_8_Chapter_OnlinePDF 195
Chapter : Growth Hormone 195
Intended Pharmacological Effect 196
Effects on Bone and GrowthHuman Growth HormoneEffects on Bone and Growth 197
Effects on Substrate Metabolism and Body Composition 197
Effects on Protein TurnoverHuman Growth HormoneEffects on Protein Turnover, Muscle Mass and Strength 198
Effects on Cardiac and Pulmonary FunctionHuman Growth HormoneEffects on Cardiac Function 198
Analytical Procedures 199
Screening and Confirmation Strategy 200
The Marker Approach 201
The Isoform Approach 202
References 204
152640_1_En_9_Chapter_OnlinePDF 209
Chapter : Mass Spectrometry-Based Analysis of IGF-1 and hGH 209
Introduction 209
IGF-1 209
Human Growth Hormone 209
References 214
152640_1_En_10_Chapter_OnlinePDF 216
Chapter : Insulin 216
Introduction 217
Pharmacological Aspects and Mode of Action 218
Endogenous Insulin Production and Storage 218
Insulin Secretion 219
Insulin Actions 220
Clinical Applications 221
Insulin Metabolism 222
Analytical Assays in Doping Control 224
Mass Spectrometry of Peptides and Proteins 224
Confirmation Methods for Synthetic Insulins 225
Case Reports 227
Conclusions 230
References 230
152640_1_En_11_Chapter_OnlinePDF 234
Chapter : beta-Adrenergic Stimulation 234
Introduction 235
Noradrenaline and the Nervous System 235
Receptor Agonists Capacities 236
Sympathomimetic Amines 237
Amphetamines and Related Compounds 238
Ephedrines 239
Strychnine and Cocaine 240
Modafinil and Adrafinil 241
Methamphetamine - Isomers: The Baxter Case 241
Bromantane 243
Pemoline 243
Methylphenidate 244
beta2-Agonists 244
Detection 246
Liquid Chromatography Mass Spectrometry (LC-MS) 250
References 253
152640_1_En_12_Chapter_OnlinePDF 257
Chapter : Erythropoietin and Analogs 257
Introduction 258
Pharmacology and Mode of Action 259
Production of Erythrocytes 259
EPO Synthesis 259
Erythropoietin Receptor 260
Isolation, Expression and Production 261
Clearance 262
Benefits and Adverse Effects 262
Erythropoietin and Analogs 263
EPO Structure 263
EPOEPOAnalogs Analogs 264
Production of Recombinant Human Erythropoietin 268
Performance Enhancement 268
Analytical Procedures and Instrumental Techniques 270
ON/OFF Model 270
Electrophoretic Methods 271
Zone Electrophoresis in Agarose Suspension 271
Isoelectric Focusing in Solution 272
Isoelectric Focusing in Polyacrylamide Slab-Gels 272
4.2.3.1General Description 272
4.2.3.2Criteria for Positivity - WADA Technical Document TD2007EPO 274
4.2.3.3Specificity of the Antibody 276
SDS-PAGE 277
2D-Electrophoresis 278
Chromatographic Methods 278
Mass Spectrometric Methods 280
Proteolytic Digestion of EPO 289
Miscellanous 290
Epo Detection Using MAIIA Technology 290
Case Report: Detection of Dynepo Administration 291
References 292
152640_1_En_13_Chapter_OnlinePDF 301
152640_1_En_14_Chapter_OnlinePDF 311
152640_1_En_15_Chapter_OnlinePDF 333
Chapter : Masking and Manipulation 333
Introduction 334
Diuretics 335
Pharmacological Mode of Action of Representative Compounds 335
Intended Pharmacological Effects 335
Biotransformation 339
Analytical Procedures, ScreeningScreening and ConfirmationConfirmation Strategy 339
Epitestosterone 344
Potential as Masking Agent 344
Biological Disposition 345
Testing for Epitestosterone Abuse in Sport 346
Probenecid 347
Inhibitors of 5a-Reductase 348
Pharmacological Aspects and Intended Use for Doping Purposes 348
Analytical Determinations 350
Plasma Expanders 350
Pharmacological Action 350
Molecular Characteristics 351
Simple Screening Approaches 351
Chromatographic and Mass Spectrometric Analysis 352
Conclusion 353
References 354
152640_1_En_16_Chapter_OnlinePDF 361
Chapter : Hormonal Growth Promoting Agents in Food Producing Animals 361
Introduction 362
Hormones in Use as Growth Promoters 363
Pharmacology and Withdrawal Times 364
Control Strategies 367
Conclusions 371
References 372
152640_1_En_17_Chapter_OnlinePDF 374
Chapter : Some Aspects of Doping and Medication Control in Equine Sports 374
Introduction 375
Technological Advances in Drug Detection 377
Knowledge of Drug MetabolismDrug Metabolism and its Significance to Drug Surveillance Programmes 378
Quality Systems and Drug Control in Sport 379
Typical Laboratory Testing Process 380
Screening 381
Confirmatory Analysis 382
The Approaches Adopted by the Racing Industry to Address Endogenous Substances and Substances of Dietary Origin 382
Salicylic Acid Threshold 384
Arsenic Threshold 385
Nandrolone Threshold 386
Theobromine Threshold 387
The Carbon Dioxide Threshold 388
Threshold Values and Article 6 of the International Agreement on Breeding, Racing and Wagering 388
Managing Threshold Values 390
Isotope Ratio Mass SpectrometryIsotope Ratio Mass Spectrometry• 391
An Approach for the Control of Therapeutic Substances in Thoroughbred Horseracing 393
Pharmacokinetic/Pharmacodynamic Assessment of Irrelevant Drug Concentrations in Equine Plasma and Urine 394
Administration and Analytical Assay Validation Studies 395
The Irrelevant Urinary Concentration and Risk Management 396
The Determination of Detection Times 396
Anabolic Steroids in the Horse 397
LC-MS Analysis in Equine Drug Testing and Metabolism 403
The Future 406
References 408
152640_1_En_18_Chapter_OnlinePDF 415
Chapter : Androgenic Anabolic Steroid Abuse and the Cardiovascular System 415
Introduction 416
Echocardiographic Studies 420
Summary 430
Hypertension 430
Summary 435
Vascular Reactivity and Vascular Function 436
Coronary CalcificationCoronary Calcification 438
Blood Platelet Function and Haemostasis 439
Lipids 444
Arrhythmias and Sudden Death 448
References 451
152640_1_En_19_Chapter_OnlinePDF 462
Chapter : Side Effects of Anabolic Androgenic Steroids: Pathological Findings and Structure-Activity Relationships 462
Methodological Limitations 463
Mechanisms of Action and Substance Specificity 463
Anabolic Effects 466
Correlation of Steroid Structure and Anabolic Effects 466
Pathological Findings 467
Bioconversion of Steroids to Characteristic Androgens and Estrogens 471
Conversion to Androgens 471
Conversion to Estrogens 472
Suppression of Endogenous Steroid Biosynthesis and Pathological Effects on the Endocrine and Reproductive System 473
Metabolic Suppression and Hepatotoxic Effects 474
Pathological Findings in the Liver 475
Lipid Metabolism 476
Neurosteroids and Psychiatric Effects 477
Biosynthesis of Neurosteroids 477
Behavioral-Psychiatric Side Effects 479
Reference 482
152640_1_En_20_Chapter_OnlinePDF 488
152640_1_En_21_Chapter_OnlinePDF 516
Chapter : Science and the Rules Governing Anti-Doping Violations 516
WADA Anti-Doping Program 519
WADA CodeWADA Code 519
Definitions of DopingDefinitions of Doping 520
Rights of Athletes 521
Antidoping Violation Resolutions 522
WADA International Standards 523
Prohibited ListProhibited List International Standard 523
International Standard for LaboratoriesInternational Standard for Laboratories 525
WADA Models of Best PracticeModels of Best Practice 527
UNESCO ConventionUNESCO Convention 527
Arbitration of Doping Rule Violations 527
Court of Arbitration for Sport 530
Evidence in Doping Rule ArbitrationArbitration 531
Laboratory Documentation of Adverse Analytical Findings 532
References 533
152640_1_En_BM2_OnlinePDF 535
: Index 535