DOCSLIB.ORG

Anabolic-Androgenic Steroids in Horses: Natural Presence and Underlying Biomechanisms

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

ANABOLIC-ANDROGENIC STEROIDS IN HORSES: NATURAL PRESENCE AND UNDERLYING BIOMECHANISMS Anneleen Decloedt Dissertation submitted in the fulfilment of the requirements for the degree of Doctor of philosophy (PhD) in Veterinary Sciences, Faculty of Veterinary Medicine, Ghent University PROMOTER Prof. dr. ir. Lynn Vanhaecke Ghent University, Faculty of Veterinary Medicine Department of Veterinary Public Health and Food Safety Laboratory of Chemical Analysis MEMBERS OF THE READING COMMITTEE Prof. dr. James Scarth HFL Sport Science, Cambridgeshire, United-Kingdom Prof. dr. Peter Van Eenoo Ghent University, DoCoLab, Zwijnaarde, Belgium Prof. dr. Ann Van Soom Ghent University, Faculty of Veterinary Medicine, Merelbeke, Belgium MEMBERS OF THE EXAMINATION COMMITTEE Dr. Ludovic Bailly-Chouriberry Laboratoires des Courses Hippiques, Verrières-le-Buisson, France Dr. Leen Van Ginkel Wageningen University, RIKILT, Wageningen, The Netherlands Prof. dr. Myriam Hesta Ghent University, Faculty of Veterinary Medicine, Merelbeke, Belgium This work was funded by the Fédération Nationale des Courses Françaises (via the Laboratoire des Courses Hippiques) and executed at the Laboratory of Chemical Analysis (Faculty of Veterinary Medicine, Ghent University, Merelbeke). The author and the promoter give the authorisation to consult and to copy parts of this work for personal use only. Every other use is subject to the copyright laws. Permission to reproduce any material contained in this work should be obtained from the author. “The universe is full of magic, Just patiently waiting for our wits to grow sharper” TABLE OF CONTENTS TABLE OF CONTENTS Chapter I – General Introduction 1 1. Steroids 3 1.1 Chemical structure 1.2 (Steroid) hormones and their role in the endocrine system 1.3 Biosynthesis of steroid hormones 1.4 Anabolic-androgenic steroids (AAS) 1.5 Synthesis and absorption of the steroid precursor cholesterol 2. Anabolic steroid abuse 12 2.1 Scientific history of anabolic steroid abuse 2.2 Residue-analysis in farm animals: regulations 2.3 Doping regulations: humans and horses 2.4 Sex steroids as registered drugs 3. Endogenous steroids 17 3.1 Reference ranges for endogenous steroids in humans 3.2 Reference ranges for endogenous steroids in horses 3.3 Hormonal disorders in horses 4. Phytosterols 22 4.1 Biological role and chemical structure 4.2 Link to anabolic steroids 5. Equine digestive tract 26 5.1 Anatomical overview 5.2 Diet 6. Analytical instrumentation 29 6.1 History 6.2 Phase I and II metabolites 6.3 UHPLC-MS/MS 6.4 GC-C-IRMS i TABLE OF CONTENTS 7. Aims 36 Chapter II – Development and validation of a UHPLC-MS/MS method to quantify low levels of anabolic-androgenic steroids naturally present in urine of untreated horses 47 1. Abstract 49 2. Introduction 50 3. Material and methods 53 3.1 Chemicals and reagents 3.2 Sample collection and extraction 3.3 Hydrolysis of the glucuro- and sulfo-conjugated compounds 3.4 Solid phase extraction, washing, and solvolysis 3.5 UHPLC-MS/MS analysis 3.6 Standard addition approach and data analysis 3.7 Quality assurance: validation of the analytical method 4. Results and discussion 59 4.1 Validation study 4.1.1 Specificity 4.1.2 Selectivity 4.1.3 Linearity 4.1.4 Precision 4.1.5 Trueness 4.1.6 Stability 4.1.7 Limit of detection and quantification 4.2 Urine screening of untreated horses 5. Conclusion 69 5.1 Executive summary Chapter III – Optimisation of phytosterol extraction and analysis from feed by D-Optimal design and UHPLC-MS/MS 75 1. Abstract 77 2. Introduction 78 ii TABLE OF CONTENTS 3. Material and methods 81 3.1 LC-MS2 reagents and chemicals 3.2 Feed and food samples 3.3 Extraction protocol optimisation 3.4 UHPLC-Triple quadrupole MS/MS analysis 3.5 Data analysis and quality assurance of the analytical method: validation according to EU Council Decision 2002/657 and AOAC guidelines 3.6 Quantitative analysis of different feed and food samples 4. Results and discussion 86 4.1 Extraction protocol optimisation 4.2 Data analysis and quality assurance of the analytical method: validation according to EU Council Decision 2002/657 and AOAC guidelines 4.2.1 Specificity 4.2.2 Selectivity 4.2.3 Calibration curves 4.2.4 Trueness: recovery 4.2.5 Precision 4.2.6 Limit of detection and quantification 4.3 Quantitative analysis of different food and feed samples 5. Conclusion 99 5.1 Highlights Chapter IV – In vitro simulation of the equine hindgut as a tool to study the influence of phytosterol consumption on the excretion of anabolic- androgenic steroids 103 1. Abstract 105 2. Introduction 106 3. Material and methods 109 3.1 LC-MS2 reagents and chemicals 3.2 In vitro digestion: batch incubations 3.2.1 Buffers and broths 3.2.2 Fecal inoculum 3.2.3 Digestion protocol and sampling iii TABLE OF CONTENTS 3.2.4 Validation of the in vitro digestion protocol 3.2.5 In vitro digestion supplements 3.2.6 Bacterial strains 3.3 Extraction of in vitro digestion and urine samples 3.3.1 Hydrolysis 3.3.2 Solid phase extraction (SPE), liquid-liquid extraction and solvolysis 3.3.3 Pooling and reconstitution 3.4 UHPLC-triple quadrupole MS/MS analysis 3.5 Quantification: data analysis and quality assurance of the analytical method 4. Results 118 4.1 Quantification: data analysis and quality assurance of the analytical method 4.2 In vitro digestion: proof of principle 4.3 Blank in vitro digestion 4.4 In vitro digestions with added steroid precursors 4.5 In vitro digestions with added phytosterols or herbal supplements 5. Discussion 129 6. Conclusion 133 Chapter V – Moldy feed, a possible explanation for the excretion of anabolic-androgenic steroids in horses? 141 1. Abstract 143 2. Introduction 144 3. Material and methods 147 3.1 LC-MS/MS reagents and chemicals 3.2 Buffers, broths and feed samples 3.3 Aerobic incubation of moldy feed 3.4 Aerobic incubation of a commercial grain mix with Mycobacterium sp. 3.5 Activity of extracellular enzymes excreted by corn-related molds 3.6 In vitro digestion of moldy feed 3.7 UHPLC-Triple Quadrupole MS/MS analysis 3.8 Data analysis, quantitative and qualitative assurance of the analytical method 4. Results 155 iv TABLE OF CONTENTS 4.1 Aerobic incubation of moldy feed 4.2 Aerobic incubation of a commercial grain mix with Mycobacterium sp. 4.3 Activity of extracellular enzymes excreted by corn-related molds 4.4 In vitro digestion of moldy feed 5. Discussion 159 6. Conclusion 164 Chapter VI – Influence of glucocorticoid treatment on the excretion of anabolic-androgenic steroids: in vitro simulations and in vivo case study 171 1. Abstract 173 2. Introduction 174 3. Material and methods 176 3.1 In vivo experimental set-up 3.2 In vitro simulation of the equine hindgut: biotransformation of glucocorticoids 3.3 LC-MS reagents and chemicals 3.4 Extraction of urine and in vitro digestion samples 3.4.1 Hydrolysis 3.4.2 Solid Phase Extraction (SPE) 3.4.3 Pooling and reconstitution 3.5 Analytical methods (UHPLC-MS/MS and UHPLC-Orbitrap-HRMS) 3.6 Quantification 4. Results 182 4.1 Urinary profile after intra-articular administration of betamethasone 4.2 In vitro digestion: biotransformation of glucocorticoids 5. Discussion 184 Chapter VII – General Discussion and Future Perspectives 191 1. Positioning of the research 193 1.1 Economical relevance of horse sports and racing v TABLE OF CONTENTS 1.2 Anabolic steroid abuse: back to the future? 1.3 Endogenous AAS: complicating doping analysis 1.4 Analytical methods to detect (endogenous) steroid abuse 2. Scientific contributions and research findings 198 2.1 Development and validation of a UHPLC-MS/MS method to quantify low levels of AAS naturally present in urine of untreated horses 2.2 Extraction optimisation, development and validation of a UHPLC-MS/MS method for the detection and quantification of phytosterols in feed 2.3 Validation of an in vitro digestion simulation of the equine hindgut as a tool to study the influence of phytosterol consumption on the excretion of anabolic- androgenic steroids in horses 2.4 Moldy feed, a possible explanation for the detection of anabolic-androgenic steroids in horses? 2.5 Influence of glucorticoid treatment on the excretion of anabolic-androgenic steroids in equine urine 3. Future perspectives 211 3.1 Endogenous steroid formation 3.2 Dietary contamination and transformation 3.3 Phytosterol-enriched feed consumption: in vivo 3.4 Mashes and silage 3.5 Influence of glucocorticoid treatment on the excretion of AAS 3.6 Equine Biological Passport Summary 225 Samenvatting 231 CV 237 Dankwoord 247 vi NOTATION INDEX NOTATION INDEX 17β-HSD 17β-hydroxysteroid dehydrogenase enzyme ∆1-SDH delta-1-steroid dehydrogenase %RSD Relative Standard Deviation αBol α-Boldenone; 17α-hydroxy-1,4-androstadiene-3-one AAS Anabolic-Androgenic Steroids ABP Athlete Biological Passport Ac-CoA Acetyl-Coenzyme A ACAT Acetyl-CoA Acetate Transferase ACTH Adrenocorticotropic hormone ADD Androstadienedione; boldione; androsta-1,4-diene-3,17-dione ADF Acid Detergent Fibre AED Androstenedione; androst-4-ene-3,17-dione AL Anterior Lobe (of the pituitary gland) AOAC Association of Official Analytical Chemists AORC Association of Official Racing Chemists ARB Australian Racing Board ASG Acylated Steryl Glycosides (phytosterol conjugates) au Arbitrary Units BCFIvet “Belgisch Centrum voor Farmacotherapeutische Informatie” BHI Brain Heart Infusion BM1 5β-androst-1-en-17β-ol-3-one BSE Bovine Spongiform Encephalopathy ßBol ß-boldenone; 17ß-hydroxy-1,4-androstadiene-3-one ßT ß-testosterone; 17ß-hydroxy-4-androstene-3-one CD Council Decision CE Collision Energy CEC Capillary Electro Chromatography CID Collision Induced Dissociation CHRB Canadian Horse Racing Board CP Crude Protein CPB Cystein Peptone Bouillon CRH Corticotrophin-releasing hormone CRM Certified Reference Material vii NOTATION INDEX DHEA Dehydroepiandrosterone DHT Dihydrotestosterone DM Dry Matter DOE Design of Experiments d.w.
Recommended publications
  • Bipolar Androgen Therapy (BAT) in Men with Prostate Cancer

    Bipolar Androgen Therapy (BAT) in Men with Prostate Cancer

    Bipolar Androgen Therapy (BAT) in men with prostate cancer Samuel Denmeade, MD Professor of Oncology, Urology and Pharmacology The Johns Hopkins University School of Medicine, Baltimore, MD Presentation Overview • Androgen and Androgen Signaling 101 • Rationale For Bipolar Androgen Therapy (BAT) • Results from the RESTORE study testing BAT in Castration Resistant Prostate Cancer • The multi-center TRANSFORMER Trial • Future Directions • Results of BATMAN trial testing BAT as part of Intermittent Hormone Therapy strategy Testosterone Replacement Anabolic Steroids Trenbolone Acetate (Fina-Finaplix H pellets) High Dose Testosterone as Treatment for Prostate Cancer What Are Androgens? • Steroid hormone which can bind to Androgen Receptor – Testosterone, Dihydrotestosterone (DHT), DHEA, Androstenedione… • Sexual Differentiation – Needed to make a Male (Female is Default) • Primary Sex Characteristics: – Spermatogenesis – Accessory Sex Tissue Maintenance • Penis, Prostate... • Secondary Sex Characteristics: – Bone density – Muscle mass – Libido – Hair growth – Hematopoiesis What is a Steroid Hormone? Testosterone (T) Dihydrotestosterone (DHT) Estrogen How are Androgens Made? Androgen Receptor Signaling 101 Androgen Active Androgen Receptor (Testosterone) Androgen Receptor How Do Androgens Effect the Prostate Cell? NTD- Signaling Part DBD- DNA Binding Part LBD- Androgen Binding Part Cytoplasm Cell Nucleus Binds and activates genes: -Cell Growth -Cell Survival -Make prostate stuff like PSA, Acid Phosphatase, etc. DNA The Devilish Prostate • Physiologic
  • Albany-Molecular-Research-Regulatory

    Albany-Molecular-Research-Regulatory

    PRODUCT CATALOGUE API COMMERCIAL US EU Japan US EU Japan API Name Site CEP India API Name Site CEP India DMF DMF DMF DMF DMF DMF A Abiraterone Malta • Benztropine Mesylate Cedarburg • Adenosine Rozzano - Quinto de' Stampi • • * Betaine Citrate Anhydrous Bon Encontre • Betametasone-17,21- Alcaftadine Spain Spain • • Dipropionate Sterile • Alclometasone-17, 21- Spain Betamethasone Acetate Spain Dipropionate • • Altrenogest Spain • • Betamethasone Base Spain Amphetamine Aspartate Rensselaer Betamethasone Benzoate Spain * Monohydrate Milled • Betamethasone Valerate Amphetamine Sulfate Rensselaer Spain * • Acetate Betamethasone-17,21- Argatroban Rozzano - Quinto de' Stampi Spain • • Dipropionate • • • Atenolol India • • Betamethasone-17-Valerate Spain • • Betamethasone-21- Atracurium Besylate Rozzano - Quinto de' Stampi Spain • Phosphate Disodium Salt • • Bromfenac Monosodium Atropine Sulfate Cedarburg Lodi * • Salt Sesquihydrate • • Azanidazole Lodi Bromocriptine Mesylate Rozzano - Quinto de' Stampi • • • • • Azelastine HCl Rozzano - Quinto de' Stampi • • Budesonide Spain • • Aztreonam Rozzano - Valle Ambrosia • • Budesonide Sterile Spain • • B Bamifylline HCl Bon Encontre • Butorphanol Tartrate Cedarburg • Beclomethasone-17, 21- Spain Capecitabine Lodi Dipropionate • C • 2 *Please contact our Accounts Managers in case you are interested in this API. 3 PRODUCT CATALOGUE API COMMERCIAL US EU Japan US EU Japan API Name Site CEP India API Name Site CEP India DMF DMF DMF DMF DMF DMF Dexamethasone-17,21- Carbimazole Bon Encontre Spain • Dipropionate
  • Expression of Recombinant Human Androgen Receptor and Its Use for Screening Methods

    Expression of Recombinant Human Androgen Receptor and Its Use for Screening Methods

    Institut für Physiologie FML Weihenstephan Technische Universität München Expression of recombinant human androgen receptor and its use for screening methods Ellinor Rose Sigrid Bauer Vollständiger Abdruck der von der Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt der Technischen Universität München zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften genehmigten Dissertation. Vorsitzender: Univ.-Prof. Dr. B. Hock Prüfer der Dissertation: Univ.-Prof. Dr. H. H. D. Meyer Univ.-Prof. Dr. H. Sauerwein (Rheinische Friedrich-Wilhelms-Universität Bonn) Die Dissertation wurde am 31.10.2002 bei der Technischen Universität München eingereicht und durch die Fakultät Wissenschaftszentrum Weihenstephan für Ernährung, Landnutzung und Umwelt am 03.12.2002 angenommen. Introduction Content 1. INTRODUCTION ..................................................................................................................................... 5 1.1. ENDOCRINE DISRUPTERS 5 1.2. ANDROGENS AND ANTIANDROGENS 7 1.2.1. DEFINITIONS 7 1.2.2. MODE OF ACTION 8 1.3. STRUCTURES OF ENDOCRINE DISRUPTERS 10 1.4. STRATEGIES FOR MONITORING ANDROGEN ACTIVE SUBSTANCES 13 1.4.1. IN VIVO METHODS 13 1.4.2. IN VITRO METHODS 15 1.5. OBJEKTIVE OF THE STUDIES 18 2. MATERIALS AND METHODS ................................................................................................................. 19 2.1. PREPARATION OF RECEPTORS 19 2.2. ASSAY SYSTEMS 19 2.2.1. IN SOLUTION AR ASSAY 19 2.2.2. IMMUNO-IMMOBILISED RECEPTOR ASSAY (IRA) 20 2.2.3. PR AND SHBG ASSAYS 21 2.2.4. DATA EVALUATION 21 2.3. ANALYTES 22 3. RESULTS AND DISCUSSION ................................................................................................................. 23 3.1. DEVELOPMENT OF NEW ASSAY SYSTEMS 23 3.1.1. BAR ASSAY 23 3.1.2. CLONING OF THE HUMAN AR AND PRODUCTION OF FUNCTIONAL PROTEIN 24 3.1.3. DEVELOPMENT OF A SCREENING ASSAY ON MICROTITRE PLATES (IRA) 25 3.2.
  • MICROCOMP Output File

    MICROCOMP Output File

    108TH CONGRESS 2D SESSION S. 2195 AN ACT To amend the Controlled Substances Act to clarify the defini- tion of anabolic steroids and to provide for research and education activities relating to steroids and steroid precursors. 1 Be it enacted by the Senate and House of Representa- 2 tives of the United States of America in Congress assembled, 3 SECTION 1. SHORT TITLE. 4 This Act may be cited as the ‘‘Anabolic Steroid Con- 5 trol Act of 2004’’. 2 1 SEC. 2. AMENDMENTS TO THE CONTROLLED SUBSTANCES 2 ACT. 3 (a) DEFINITIONS.—Section 102 of the Controlled 4 Substances Act (21 U.S.C. 802) is amended— 5 (1) in paragraph (41)— 6 (A) by realigning the margin so as to align 7 with paragraph (40); and 8 (B) by striking subparagraph (A) and in- 9 serting the following: 10 ‘‘(A) The term ‘anabolic steroid’ means any drug or 11 hormonal substance, chemically and pharmacologically re- 12 lated to testosterone (other than estrogens, progestins, 13 corticosteroids, and dehydroepiandrosterone), and 14 includes— 15 ‘‘(i) androstanediol— 16 ‘‘(I) 3β,17β-dihydroxy-5α-androstane; and 17 ‘‘(II) 3α,17β-dihydroxy-5α-androstane; 18 ‘‘(ii) androstanedione (5α-androstan-3,17- 19 dione); 20 ‘‘(iii) androstenediol— 21 ‘‘(I) 1-androstenediol (3β,17β-dihydroxy- 22 5α-androst-1-ene); 23 ‘‘(II) 1-androstenediol (3α,17β-dihydroxy- 24 5α-androst-1-ene); 25 ‘‘(III) 4-androstenediol (3β,17β-dihydroxy- 26 androst-4-ene); and †S 2195 ES 3 1 ‘‘(IV) 5-androstenediol (3β,17β-dihydroxy- 2 androst-5-ene); 3 ‘‘(iv) androstenedione— 4 ‘‘(I) 1-androstenedione ([5α]-androst-1-en- 5 3,17-dione);
  • Quick Determination of 105 Doping in Animal Derived Food By

    Quick Determination of 105 Doping in Animal Derived Food By

    QTRAP®质谱系统对动物源食品中105种兴奋剂的快速分析 检测 Quick Determination of 105 Doping in Animal – derived Food by QTRAP® System 杨总1，陈丹2，程海燕1，李立军1，郭立海1 Yang Zong1，Chen Dan2，Cheng Haiyan1，Li Lijun1，Guo Lihai1 1 SCIEX亚太应用支持中心，上海； 2 湖北省武汉食品化妆品检验所 1 SCIEX Asia Pacific Application Support Center, Shanghai, China; 2 Wuhan Institute for Food and Cosmetic Control, Hubei Province, China; Keywords：doping；SCIEX QTRAP® 4500 系统； LC-MS/ MS；quantitative analysis 引言 在现代畜牧养殖业中，一些不法分子长期使用各种饲料添加 剂和人工合成激素类化合物，造成动物源食品中的药物残留，最 终成为食源性兴奋剂的来源[1]。运动员食用含有某些药物残留的食 物，可导致其兴奋剂检测呈阳性。国家反兴奋剂中心和世界反兴 奋剂机构（WADA）等组织机构明确规定了兴奋剂的违禁药物的种 SCIEX ExionLC™液相和SCIEX QTRAP® 4500质谱系统 类，主要包含了β-受体激动剂、固醇类激素、糖皮质激素、利尿 剂、玉米赤霉醇类等等。总体而言，兴奋剂的作用主要是对身体或 者中枢神经系统起到选择性的作用，能促进肌肉组织快速增长、增 4. 建立好了105种兴奋剂EPI二级谱库，软件自动进行匹配二级质 强机体活力和敏捷度，还可使运动员疲劳减轻，自信心增强，注意 谱图，保证筛查结果准确可靠； 力集中[2]。因此在体育赛事过程中，为了保证赛事结果的公平、公 正，在运动员食品安全保障过程中，必须对食品中兴奋剂进行严格 5. 方法现成，省去开发方法的时间，提高了工作效率； 的监控。本文针对动物源食品中的常见105种兴奋剂，建立了采用 QTRAP®系统快速筛查和定量方法，该方法完全满足在体育赛事过 1. 实验方法 程中对兴奋剂监管的分析要求。 1.1 液相色谱条件 该方案的特点和优势 色谱柱：Phenomenex Kinetex 2.6µm F5 100 Å 150×3 µm 流动相：水相（水中含有5 mM乙酸铵和0.01%甲酸），有机 1. 方法覆盖面广，包含了常见五大类β-受体激动剂、固醇类激 相为乙腈，梯度洗脱 素、糖皮质激素、利尿剂、玉米赤霉醇类兴奋剂，共105种； 1.2 质谱条件 2. 本实验详细优化了前处理过程，考察了化合物的稳定性； 扫描模式：MRM-IDA-EPI，正负离子同时扫描，MRM离子对见 3. 实验采用MRM-IDA-EPI扫描实现一针进样同时定量和定性分 表1。 析，快速灵敏，满足国内外标准品的要求； RUO-MKT-02-9756-ZH-A p 1 离子源：ESI源；离子源参数：喷雾电压（IS）：5500V（+） 2. 结果与讨论 /-4500V（-）；离子源温度：600℃；气帘气（CUR）：35psi；碰 2.1 前处理过程的优化 撞气（CAD）：Medium；雾化气（GS1）：55psi；辅助雾化气 （GS2）：60psi 本实验详细优化了前处理过程，实验结果表明在动物源食品 中酸化乙腈的提取效率最高，绝大部分化合物回收率在70%以上 1.3 样品前处理过程 （见图1、图2、图3）。由于基质的复杂性，实验比较了5种不同 称取5g样品于50 mL离心管 → 加入10 mL乙酸铵缓冲溶液混 的SPE柱的净化效率，由图4可以看出，PRIME HLB 净化效果最优 异，回收率较高。 匀 → 加入β-葡萄糖醛甙酶进行酶解 → 加入酸化乙腈进行提取， 震荡混匀后加入NaCl和Mg2SO4 → 萃取之后高速离心取上清液采用 PRIME HLB进行净化 → 吹干后复溶上机测试。 100 80 60 40 20 0 酸化叔丁基甲醚 酸化乙腈 碱化乙腈 图1.
  • A10 Anabolic Steroids Hardcore Info

    A10 Anabolic Steroids Hardcore Info

    CONTENTS GENERAL INFORMATION 3 Anabolic steroids – What are they? 4 How do they Work? – Aromatisation 5 More molecules – More problems 6 The side effects of anabolic steroids 7 Women and anabolic steroids 8 Injecting steroids 9 Abscesses – Needle Exchanges 10 Intramuscular injection 11 Injection sites 12 Oral steroids – Cycles – Stacking 13 Diet 14 Where do steroids come from? Spotting a counterfeit 15 Drug Information – Drug dosage STEROIDS 16 Anadrol – Andriol 17 Anavar – Deca-Durabolin 18 Dynabolon – Durabolin – Dianabol 19 Esiclene – Equipoise 20 Primobolan Depot – Proviron – Primobolan orals – Pronobol 21 Sustanon – Stromba, Strombaject – Testosterone Cypionate Testosterone Enanthate 22 Testosterone Propionate – Testosterone Suspension 23 Trenbolone Acetate – Winstrol OTHER DRUGS 24 Aldactone – Arimidex 25 Clenbuterol – Cytomel 26 Ephedrine Hydrochloride – GHB 27 Growth Hormone 28 Insulin 30 Insulin-Like Growth Factor-1 – Human Chorionic Gonadotrophin 31 Tamoxifen – Nubain – Recreational Drugs 32 Steroids and the Law 34 Glossary ANABOLIC STEROIDS People use anabolic steroids for various reasons, some use them to build muscle for their job, others just want to look good and some use them to help them in sport or body building. Whatever the reason, care needs to be taken so that as little harm is done to the body as possible because despite having muscle building effects they also have serious side effects especially when used incorrectly. WHAT ARE THEY? Anabolic steroids are man made versions of the hormone testosterone. Testosterone is the chemical in men responsible for facial hair, deepening of the voice and sex organ development, basically the masculine things Steroids are in a man. used in medicine to treat anaemia, muscle weakness after These masculine effects surgery etc, vascular are called the androgenic disorders and effects of testosterone.
  • 2010 Prohibited List

    2010 Prohibited List

    The World Anti-Doping Code THE 2010 PROHIBITED LIST INTERNATIONAL STANDARD The official text of the Prohibited List shall be maintained by WADA and shall be published in English and French. In the event of any conflict between the English and French versions, the English version shall prevail. This List shall come into effect on 1 January 2010 The Prohibited List 2010 19 September 2009 THE 2010 PROHIBITED LIST WORLD ANTI-DOPING CODE Valid 1 January 2010 All Prohibited Substances shall be considered as “Specified Substances” except Substances in classes S1, S2.1 to S2.5, S.4.4 and S6.a, and Prohibited Methods M1, M2 and M3. SUBSTANCES AND METHODS PROHIBITED AT ALL TIMES (IN- AND OUT-OF-COMPETITION) PROHIBITED SUBSTANCES S1. ANABOLIC AGENTS Anabolic agents are prohibited. 1. Anabolic Androgenic Steroids (AAS) a. Exogenous* AAS, including: 1-androstendiol (5α-androst-1-ene-3β,17β-diol ); 1-androstendione (5α- androst-1-ene-3,17-dione); bolandiol (19-norandrostenediol); bolasterone; boldenone; boldione (androsta-1,4-diene-3,17-dione); calusterone; clostebol; danazol (17α-ethynyl-17β-hydroxyandrost-4-eno[2,3-d]isoxazole); dehydrochlormethyltestosterone (4-chloro-17β-hydroxy-17α-methylandrosta- 1,4-dien-3-one); desoxymethyltestosterone (17α-methyl-5α-androst-2-en- 17β-ol); drostanolone; ethylestrenol (19-nor-17α-pregn-4-en-17-ol); fluoxymesterone; formebolone; furazabol (17β-hydroxy-17α-methyl-5α- androstano[2,3-c]-furazan); gestrinone; 4-hydroxytestosterone (4,17β- dihydroxyandrost-4-en-3-one); mestanolone; mesterolone; metenolone; methandienone
  • Control Substance List

    Control Substance List

    Drugs DrugID SubstanceName DEANumbScheNarco OtherNames 1 1-(1-Phenylcyclohexyl)pyrrolidine 7458 I N PCPy, PHP, rolicyclidine 2 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine 9663 I Y PEPAP, synthetic heroin 3 1-[1-(2-Thienyl)cyclohexyl]piperidine 7470 I N TCP, tenocyclidine 4 1-[1-(2-Thienyl)cyclohexyl]pyrrolidine 7473 I N TCPy 5 13Beta-ethyl-17beta-hydroxygon-4-en-3-one 4000 III N 6 17Alpha-methyl-3alpha,17beta-dihydroxy-5alpha-androstane 4000 III N 7 17Alpha-methyl-3beta,17beta-dihydroxy-5alpha-androstane 4000 III N 8 17Alpha-methyl-3beta,17beta-dihydroxyandrost-4-ene 4000 III N 9 17Alpha-methyl-4-hydroxynandrolone (17alpha-methyl-4-hyd 4000 III N 10 17Alpha-methyl-delta1-dihydrotestosterone (17beta-hydroxy- 4000 III N 17-Alpha-methyl-1-testosterone 11 19-Nor-4-androstenediol (3beta,17beta-dihydroxyestr-4-ene; 4000 III N 12 19-Nor-4-androstenedione (estr-4-en-3,17-dione) 4000 III N 13 19-Nor-5-androstenediol (3beta,17beta-dihydroxyestr-5-ene; 4000 III N 14 19-Nor-5-androstenedione (estr-5-en-3,17-dione) 4000 III N 15 1-Androstenediol (3beta,17beta-dihydroxy-5alpha-androst-1- 4000 III N 16 1-Androstenedione (5alpha-androst-1-en-3,17-dione) 4000 III N 17 1-Methyl-4-phenyl-4-propionoxypiperidine 9661 I Y MPPP, synthetic heroin 18 1-Phenylcyclohexylamine 7460 II N PCP precursor 19 1-Piperidinocyclohexanecarbonitrile 8603 II N PCC, PCP precursor 20 2,5-Dimethoxy-4-(n)-propylthiophenethylamine 7348 I N 2C-T-7 21 2,5-Dimethoxy-4-ethylamphetamine 7399 I N DOET 22 2,5-Dimethoxyamphetamine 7396 I N DMA, 2,5-DMA 23 3,4,5-Trimethoxyamphetamine
  • (12) Patent Application Publication (10) Pub. No.: US 2008/0063698 A1 Hartwig (43) Pub

    (12) Patent Application Publication (10) Pub. No.: US 2008/0063698 A1 Hartwig (43) Pub

    US 2008 OO63698A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2008/0063698 A1 Hartwig (43) Pub. Date: Mar. 13, 2008 (54) CRYSTALLIZATION INHIBITION OF DRUGS now abandoned, which is a continuation of applica IN TRANSIDERMAL DRUG DELIVERY tion No. 10/010,342, filed on Dec. 5, 2001, now SYSTEMIS AND METHODS OF USE abandoned. (75) Inventor: Rod Lawson Hartwig, Plantation, FL (60) Provisional application No. 60/251.294, filed on Dec. (US) 5, 2000. Correspondence Address: Publication Classification Noven Pharmaceuticals, Inc. Jay G. Kolman, Esq. (51) Int. Cl. 11960 S.W. 144 Street A6II 3/56 (2006.01) A6F 3/00 (2006.01) Miami, FL 33186 (US) A6IP 43/00 (2006.01) (73) Assignee: NOVEN PHARMACEUTICALS, A6F 3/02 (2006.01) INC. (52) U.S. Cl. ........................... 424/448; 424/449; 514/170 (57) ABSTRACT Appl. No.: 11/897,189 (21) The invention relates to compositions and methods for (22) Filed: Aug. 29, 2007 making a transdermal drug delivery system capable of achieving substantially zero-order kinetics for delivery of Related U.S. Application Data the active agent over a period of time in excess of 24 hours and at least 72 hours, comprising a pharmaceutically accept (63) Continuation of application No. 10/751,152, filed on able active agent carrier and a rosin ester which provides a Jan. 2, 2004, now abandoned, which is a continuation crystal inhibiting and drug stabilizing effect on the active of application No. 10/353,624, filed on Jan. 29, 2003, agents incorporated therein. 13 2 2 Patent Application Publication Mar.
  • General Agreement on Tariffs Andtrade

    General Agreement on Tariffs Andtrade

    RESTRICTED GENERAL AGREEMENT TAR/W/87/Rev.1 16 June 1994 ON TARIFFS AND TRADE Limited Distribution (94-1266) Committee on Tariff Concessions HARMONIZED COMMODITY DESCRIPTION AND CODING SYSTEM (Harmonized System) Classification of INN Substances Revision The following communication has been received from the Nomenclature and Classification Directorate of the Customs Co-operation Council in Brussels. On 25 May 1993, we sent you a list of the INN substances whose classification had been discussed and decided by the Harmonized System Committee. At the time, we informed you that the classification of two substances, clobenoside and meclofenoxate, would be decided later. Furthermore, for some of the chemicals given in that list, one of the contracting parties had entered a reservation and the Harmonized System Committee therefore reconsidered its earlier decision in those cases. I am therefore sending you herewith a revised complete list of the classification decisions of the INN substances. In this revised list, two substances have been added and the classifications of two have been revised as explained below: (a) Addition Classification of clobenoside, (subheading 2940.00) and meclofenoxate (subheading 2922.19). (b) Amendment Etafedrine and moxidentin have now been reclassified in subheadings 2939.40 and 2932.29 respectively. The list of INN substances reproduced hereafter is available only in English. TAR/W/87/Rev. 1 Page 2 Classification of INN Substances Agreed by the Harmonized System Committee in April 1993 Revision Description HS Code
  • Prohibited List

    Prohibited List

    PROHIBITED LIST This List shall come into effect on 1 January 201X THE 201X PROHIBITED LIST Valid 1 January 201X In accordance with ARCI-011-015/ARCI-025-015 all substances in the categories below shall be strictly prohibited unless otherwise noted. Any reference to substances in this section does not alter the requirements for testing concentrations in race day samples. SUBSTANCES AND METHODS PROHIBITED AT ALL TIMES (IN- AND OUT-OF-COMPETITION) PROHIBITED SUBSTANCES Nothing in this list shall alter the requirements of post-race testing. S0. NON-APPROVED SUBSTANCES Any pharmacologic substance which is not addressed by any of the subsequent sections of the List and with no current approval by any governmental regulatory health authority for human or veterinary use (e.g., drugs under pre-clinical or clinical development, discontinued drugs, and designer drugs) is prohibited at all times. S00. THERAPEUTIC SUBSTANCES Therapeutic substances that are not otherwise prohibited pursuant to this list are permitted provided such substances: Have current approval for use in human, horse, or other animal by any governmental regulatory health authority in the jurisdiction where the horse is located S1. ANABOLIC AGENTS Anabolic agents are prohibited. 1. Anabolic Androgenic Steroids (AAS) 1.1. Exogenous* AAS, including: 1-androstenediol (5α-androst-1-ene-3β,17β-diol ); 1-androstenedione (5α- androst-1-ene-3,17-dione); bolandiol (estr-4-ene-3β,17β-diol ); bolasterone; boldenone; boldione (androsta-1,4-diene-3,17-dione); calusterone; clostebol; danazol
  • A20-0767), As Follows:​

    A20-0767), As Follows:​

    05/05/20 03:02 pm ​ HOUSE RESEARCH JD/RK H2711A8​ 1.1 .................... moves to amend H.F. No. 2711, the delete everything amendment​ 1.2 (A20-0767), as follows:​ 1.3 Page 21, delete section 1​ 1.4 Page 36, delete section 2​ 1.5 Page 40, delete section 3 and insert:​ 1.6 "Section 1. Minnesota Statutes 2018, section 152.02, subdivision 2, is amended to read:​ 1.7 Subd. 2. Schedule I. (a) Schedule I consists of the substances listed in this subdivision.​ 1.8 (b) Opiates. Unless specifically excepted or unless listed in another schedule, any of the​ 1.9 following substances, including their analogs, isomers, esters, ethers, salts, and salts of​ 1.10 isomers, esters, and ethers, whenever the existence of the analogs, isomers, esters, ethers,​ 1.11 and salts is possible:​ 1.12 (1) acetylmethadol;​ 1.13 (2) allylprodine;​ 1.14 (3) alphacetylmethadol (except levo-alphacetylmethadol, also known as levomethadyl​ 1.15 acetate);​ 1.16 (4) alphameprodine;​ 1.17 (5) alphamethadol;​ 1.18 (6) alpha-methylfentanyl benzethidine;​ 1.19 (7) betacetylmethadol;​ 1.20 (8) betameprodine;​ 1.21 (9) betamethadol;​ Section 1.​ 1​ 05/05/20 03:02 pm ​ HOUSE RESEARCH JD/RK H2711A8​ 2.1 (10) betaprodine;​ 2.2 (11) clonitazene;​ 2.3 (12) dextromoramide;​ 2.4 (13) diampromide;​ 2.5 (14) diethyliambutene;​ 2.6 (15) difenoxin;​ 2.7 (16) dimenoxadol;​ 2.8 (17) dimepheptanol;​ 2.9 (18) dimethyliambutene;​ 2.10 (19) dioxaphetyl butyrate;​ 2.11 (20) dipipanone;​ 2.12 (21) ethylmethylthiambutene;​ 2.13 (22) etonitazene;​ 2.14 (23) etoxeridine;​ 2.15 (24) furethidine;​