Doping in Sports

152640_1_En_1_Chapter_OnlinePDF

Chapter : History of Doping and Doping Control

The Expression ``Doping´´

Early Attempts of Doping

Doping and its Emerging Prohibition

Stimulants

Anabolic Agents

Fatalities with Presumptive Correlation to Doping

Development of General Anti-Doping Regulations

Doping Analysis and Accreditation of Anti-Doping Laboratories

Doping and the Cold War

Developments from the 1990s Onward

Appendix 1 Historical Definitions of Doping

References

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Chapter : Phase-II Metabolism of Androgens and Its Relevance for Doping Control Analysis

Phase-II Metabolism of Androgens

Glucuronide Conjugation

Sulphonation

Genetic Polymorphism

Relevance of Phase-II Metabolism in Doping Control Analysis

In Vitro Production of Phase-II Metabolites

References

152640_1_En_4_Chapter_OnlinePDF

Chapter : Detecting the Administration of Endogenous Anabolic Androgenic SteroidsAnabolic Androgenic SteroidsEndogenous

Introduction

Testosterone

Historical Background

General Approach to the Measurement of Urinary Steroids

From Immunoassays to Mass Spectrometry

Sample Preparation for GC/MS Analyses

Stability of Urinary Steroid Conjugates

Testosterone and Epitestosterone

Reference Ranges

Stability of Individual Parameters

Alteration of the Urinary Steroid Profile

Testosterone

Dihydrotestosterone, Androstenedione and Dehydroepiandrosterone

Measurement of the delta13C Values of Urinary Steroid Metabolites

Principle of the GC/C/IRMS Analysis

IRMS for Determining the Origin of Organic Compounds

delta13C Values of Urinary Steroid Metabolites

External Factors Influencing the GC/MS Steroid Profile

Anabolic Agents and Inhibitors of Reductase

Ethanol

Supplements

From Population-Based to Subject-Based Testing Approach

References

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Chapter : Synthetic Anabolic Agents: Steroids and Nonsteroidal Selective Androgen Receptor Modulators

Introduction

Pharmacological Aspects and Mode of Action of AAS

Mode of Action of AAS

Metabolism of AAS

Methyltestosterone and Metandienone

Stanozolol

Undesirable Effects of AAS

Cardiovascular Issues

Endocrine Issues

Hepatic Issues

Psychiatric Issues

Musculoskeletal Issues

Pharmacological Aspects and Mode of Action of SARMs

Metabolism of SARMs

Clinical Applications

Undesirable Effects of SARMs

Detection Strategies for AAS and SARMs

Sample Preparation and Analysis of AAS

GC-MS Analyses

LC-MS(/MS) Analyses

Sample Preparation and Analysis of SARMs

Conclusions

References

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Chapter : Designer Steroids

Introduction

Exogenous SteroidsSteroidsExogenous

Endogenous SteroidsSteroidsEndogenous

BALCO, an Insight into Conspiracy

Anabolic Steroid Chemistry

Detection Methods

Use of Gas Chromatography-Mass Spectrometry (GC-MS)

Use of LC-MS(/MS)

The Supplement Market

Conclusion

References

152640_1_En_8_Chapter_OnlinePDF

Chapter : Growth Hormone

Intended Pharmacological Effect

Effects on Bone and GrowthHuman Growth HormoneEffects on Bone and Growth

Effects on Substrate Metabolism and Body Composition

Effects on Protein TurnoverHuman Growth HormoneEffects on Protein Turnover, Muscle Mass and Strength

Effects on Cardiac and Pulmonary FunctionHuman Growth HormoneEffects on Cardiac Function

Analytical Procedures

Screening and Confirmation Strategy

The Marker Approach

The Isoform Approach

References

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Chapter : Mass Spectrometry-Based Analysis of IGF-1 and hGH

Introduction

IGF-1

Human Growth Hormone

References

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Chapter : Insulin

Introduction

Pharmacological Aspects and Mode of Action

Endogenous Insulin Production and Storage

Insulin Secretion

Insulin Actions

Clinical Applications

Insulin Metabolism

Analytical Assays in Doping Control

Mass Spectrometry of Peptides and Proteins

Confirmation Methods for Synthetic Insulins

Case Reports

Conclusions

References

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Chapter : beta-Adrenergic Stimulation

Introduction

Noradrenaline and the Nervous System

Receptor Agonists Capacities

Sympathomimetic Amines

Amphetamines and Related Compounds

Ephedrines

Strychnine and Cocaine

Modafinil and Adrafinil

Methamphetamine - Isomers: The Baxter Case

Bromantane

Pemoline

Methylphenidate

beta2-Agonists

Detection

Liquid Chromatography Mass Spectrometry (LC-MS)

References

152640_1_En_12_Chapter_OnlinePDF

Chapter : Erythropoietin and Analogs

Introduction

Pharmacology and Mode of Action

Production of Erythrocytes

EPO Synthesis

Erythropoietin Receptor

Isolation, Expression and Production

Clearance

Benefits and Adverse Effects

Erythropoietin and Analogs

EPO Structure

EPOEPOAnalogs Analogs

Production of Recombinant Human Erythropoietin

Performance Enhancement

Analytical Procedures and Instrumental Techniques

ON/OFF Model

Electrophoretic Methods

Zone Electrophoresis in Agarose Suspension

Isoelectric Focusing in Solution

Isoelectric Focusing in Polyacrylamide Slab-Gels

4.2.3.1General Description

4.2.3.2Criteria for Positivity - WADA Technical Document TD2007EPO

4.2.3.3Specificity of the Antibody

SDS-PAGE

2D-Electrophoresis

Chromatographic Methods

Mass Spectrometric Methods

Proteolytic Digestion of EPO

Miscellanous

Epo Detection Using MAIIA Technology

Case Report: Detection of Dynepo Administration

References

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Chapter : Masking and Manipulation

Introduction

Diuretics

Pharmacological Mode of Action of Representative Compounds

Intended Pharmacological Effects

Biotransformation

Analytical Procedures, ScreeningScreening and ConfirmationConfirmation Strategy

Epitestosterone

Potential as Masking Agent

Biological Disposition

Testing for Epitestosterone Abuse in Sport

Probenecid

Inhibitors of 5a-Reductase

Pharmacological Aspects and Intended Use for Doping Purposes

Analytical Determinations

Plasma Expanders

Pharmacological Action

Molecular Characteristics

Simple Screening Approaches

Chromatographic and Mass Spectrometric Analysis

Conclusion

References

152640_1_En_16_Chapter_OnlinePDF

Chapter : Hormonal Growth Promoting Agents in Food Producing Animals

Introduction

Hormones in Use as Growth Promoters

Pharmacology and Withdrawal Times

Control Strategies

Conclusions

References

152640_1_En_17_Chapter_OnlinePDF

Chapter : Some Aspects of Doping and Medication Control in Equine Sports

Introduction

Technological Advances in Drug Detection

Knowledge of Drug MetabolismDrug Metabolism and its Significance to Drug Surveillance Programmes

Quality Systems and Drug Control in Sport

Typical Laboratory Testing Process

Screening

Confirmatory Analysis

The Approaches Adopted by the Racing Industry to Address Endogenous Substances and Substances of Dietary Origin

Salicylic Acid Threshold

Arsenic Threshold

Nandrolone Threshold

Theobromine Threshold

The Carbon Dioxide Threshold

Threshold Values and Article 6 of the International Agreement on Breeding, Racing and Wagering

Managing Threshold Values

Isotope Ratio Mass SpectrometryIsotope Ratio Mass Spectrometry•

An Approach for the Control of Therapeutic Substances in Thoroughbred Horseracing

Pharmacokinetic/Pharmacodynamic Assessment of Irrelevant Drug Concentrations in Equine Plasma and Urine

Administration and Analytical Assay Validation Studies

The Irrelevant Urinary Concentration and Risk Management

The Determination of Detection Times

Anabolic Steroids in the Horse

LC-MS Analysis in Equine Drug Testing and Metabolism

The Future

References

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Chapter : Androgenic Anabolic Steroid Abuse and the Cardiovascular System

Introduction

Echocardiographic Studies

Summary

Hypertension

Summary

Vascular Reactivity and Vascular Function

Coronary CalcificationCoronary Calcification

Blood Platelet Function and Haemostasis

Lipids

Arrhythmias and Sudden Death

References

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Chapter : Side Effects of Anabolic Androgenic Steroids: Pathological Findings and Structure-Activity Relationships

Methodological Limitations

Mechanisms of Action and Substance Specificity

Anabolic Effects

Correlation of Steroid Structure and Anabolic Effects

Pathological Findings

Bioconversion of Steroids to Characteristic Androgens and Estrogens

Conversion to Androgens

Conversion to Estrogens

Suppression of Endogenous Steroid Biosynthesis and Pathological Effects on the Endocrine and Reproductive System

Metabolic Suppression and Hepatotoxic Effects

Pathological Findings in the Liver

Lipid Metabolism

Neurosteroids and Psychiatric Effects

Biosynthesis of Neurosteroids

Behavioral-Psychiatric Side Effects

Reference

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152640_1_En_21_Chapter_OnlinePDF

Chapter : Science and the Rules Governing Anti-Doping Violations

WADA Anti-Doping Program

WADA CodeWADA Code

Definitions of DopingDefinitions of Doping

Rights of Athletes

Antidoping Violation Resolutions

WADA International Standards

Prohibited ListProhibited List International Standard

International Standard for LaboratoriesInternational Standard for Laboratories

WADA Models of Best PracticeModels of Best Practice

UNESCO ConventionUNESCO Convention

Arbitration of Doping Rule Violations

Court of Arbitration for Sport

Evidence in Doping Rule ArbitrationArbitration

Laboratory Documentation of Adverse Analytical Findings

References

152640_1_En_BM2_OnlinePDF

: Index