Drug Testing at the loth Asian Games and 24th Seoul Olympic Games

Drug Testing at the loth Asian Games and 24th Seoul Olympic Games Jongsei Park*, Songja Park, Dongseok Lho, Haeyoung P. Choo, Bongchull Chung, Changno Yoon, Hongki Min, and Myung Ja Choi Doping Control Center, Korea Institute of Science & Technology, P.O. Box 131, Cheongryang, Seoul, Korea Abstract ] Drug testing (doping test) procedures in the 1986 10th Asian Olympic Games and 1988 24th SeouI Olympic Games ere reported. The International Olympic Committee Medicel Commission (IOC-MC) conducted its first doping tests at the 1968 Olympics In Grenoble. With the guidence of the Internetional Olympic Committee (IOC), the Olympic Council of Asia (OCA) Introduced' doping tests at the 1986 10th Asian Olympic Games in Seoul, Koree, September 21st to October 5th, 1986. 585 samples were tested at the Doping Control Center, Korea Advanced Institute of Science and Technology (DCC/KAIST), for eumulants, narcotics, anabolic steroids, and beta-blockers by gas chromatography/masa spectrometry, high pressure liquid chromatography, and fluorescence polarization immunoasaay. These tests covered about 100 different drugs and another 400 as metebolltes In addition to pharmacologically related substances. For the Seoul Olympic Games from September 17 to October 2, 1988, the IOC-MC with the OCC/KAIST conducted doping tests on 1601 samples for stimulants, narcotics, beta-blockers, diuretics, and anabolic steroids using GC, HPLC, GC/MSD, GC/MS, LC/MS, and TDx. Introduction The word "dope" has its origin in the Kafir tribe of Africa (1). They used brandy made from grapes as a stimulant during ceremonial dances, and it is called "dop" in Afrikans. From there it found its way into the English dictionary in the late 1800s, referring to a mixture of opium and other narcotics used with horses. Recently, the International Olympic Committee and the International Amatuer Athletic Federation defined doping as the use by or distribution to an athlete of certain substances which could have the effect of improving artificially the athlete's physical or mental condition and so improving his athletic performance. For over 2000 years, doping has continued and despite ethical scandals, deaths, chronic illness, and regulatory rules, the industry is alive and well. Documented cases of dope use 9 Author to whom requests for reprints should be addressed. during international sporting events were noted in every modern International Olympic Games and regional continental Olympic Games such as the Pan-Am Games, the Asian Games, and the Commonwealth Games. Testing for doping substances at the Olympic Games was officially started during the 1968 Grenoble (France) Winter Olympics. Due to the analytical techniques available at that time, only a few stimulants and narcotics were checked, these being the most widely abused substances among athletes at that time (2). At the 1976 Montreal Olympic Games anabolic steroids were added as screened substances. About 15% of the specimens were tested for anabolic steroids at that time. During the 1980 Moscow Olympic Games, half of the specimens were tested for anabolic steroids. Analytical techniques for the detection of anabolic steroids by gas chromatography/mass spectrometry (GC/MS) had advanced enough since that time so that all specimens were tested for anabolic steroids by GC/MS at the 1984 Los Angeles Olympic Games (3). The International Olympic Committee Medical Commission (IOC-MC) is responsible for curbing the abuse of doping agents and has developed a list of banned substances. This list is updated as the underground drug scene continually changes and the IOC-MC, in this respect, developed lists of banned substances for the 1984 L.A. Olympics, 1986 Seoul Asian Games, 1987 Indianapolis Pan-Am Games, and the 1988 Seoul Olympic Games (refer to banned drug lists). The doping control center (DCC) of the Korea Advanced Institute of Science and Technology (KAIST) was asked to conduct doping tests for the 1986 Seoul Asian Games by the Seoul Asian Games Organizing Committee (SAGOC) and for the 1988 Seoul Olympic Games by the Seoul Olympic Organizing Committee (SLOOC), whereupon in 1984 the DCC began to purchase the necessary analytical equipment (mainly for gas chromatography with capillary columns and nitrogen-phosphorous detection, gas chromatography/mass spectrometry, high pressure liquid chromatography and fluorescence polarization immunoassay systems). The equipment used for the doping analysis for the 1986 Asian Games (585 samples) and for the 1988 Olympic Games (1601 samples) during 15 consecutive days for each and its specifications are listed in Table I. Control of complex data interchange among instruments was facilitated with a laboratory computer. The DCC has a staff of 30 scientists consisting of 7 Ph.D.s in toxicology, chemistry, and pharmacology, 20 M.S.s, and 3 B.S.s in chemistry or biological sciences. 66 Reproduction (photocopying) of editorial content of this journal is prohibited without publisher's permission.

Table I. Analytical Equipment Used for the 1986 Asian Games and 1988 Seoul Olympic Games instrument Model Asian Games Olympic Games Gas Chromatograph/Mass Selective Detector Gas Chromatograph High-Performance Liquid Chromatograph Gas Chromatograph/Mass Spectrometer Liquid Chromatograph-Mass Spectrometer Laboratory Automation System Ultraviolet/Visible Spectrophotometer Gamma-Counter Liquid Scintillation Counter Automatic Fluorescence Analyzer HP 5890A/5970B 6 12 HP 5890A 4 7 HP 1090A 3 6 HP 5890A/5988A 1 1 HP 1090L/5988A 1 1 HP 59870B 1 1 HP 8451A 1 1 Packard 5550 1 1 Packard 2000CA 1 1 TDx system, Abbott Laboratories 1 4 Procedure Sample acquisition and analysis Collection of urine specimens is the responsibility of the Games Organizing Committee. A doping control collection team at each venue consisted of one doping control coordinator (medical doctor), two to eight doping control escorts (interpreters), two to six doping control technicians, minimum one male and one female, one security guard, and one courier. The doping control station at each venue was divided into three sections, the total area ranging from 19.8 to 115.5 square meters, and averaging 54 square meters. The three sections were a sample processing room, a waiting room, and a toilet facility. An agreement was made between the OCA and International Federations (IF) for the '86 Games and '88 Games, that the International Federations of each sport be involved with the Organizing Committee in the selection of the athletes to be tested. Even though there was a slight variation in policy of how to select the athletes, in most cases, it was the three medal winners, 4th and 5th places, and one randomly selected, totaling six athletes for each event. For team sports such as football or handball, three or four players were randomly selected. As soon as each event was over, selected athletes were notified, and the competitor, under supervision of the doping control escort, was asked to come to the doping station within an hour. Athletes were asked to void a minimum of 75 ml into a 100-mL glass bottle (A) and even though they were allowed to go wherever they desired including restaurants to have a meal to help them void more easily, they were under constant supervision until they could void the minimum amount. When a minimum amount of urine was obtained, 89 of it was transferred to another bottle (B). Bottles A and B were then put into different bags with a drug declaration form which was sealed in the presence of the athlete. This form contained the code number of the athlete, and a list of drugs which the athlete had taken in the past three days. Each bag was then placed into a transfer bag and transported to the DCC. Each bag and bottles inside were identified through their code number and the identity of the code was known only to the OCA-MC chairman (or IOC-MC chairman). Accordingly, the laboratory would analyze each specimen without knowing its identity. The DCC staff opened the bag and bottle B was locked in a refrigerator whose key was controlled by an OCA-MC (or IOC-MC) member. Bottle A was opened and its volume, color, density, and ph were measured and recorded. The urine specimen was then divided into 5 different tubes (one tube for each procedure) and analyzed for the presence of doping agent(s). The results were reported daily to the OCA-MC/IOC-MC within 24 h after International Olympic Committee Banned Drug List (1984 L.A. Olympic Games) Psychomotor stimulants Amphetamine Benzphetamine Chlorphentermine Cocaine Diethylpropion Dimethylamphetamine Ethylamphetamine Fencamfamin Meclofenoxate Methylamphetamine Narcotic analgesics Anileridine Codeine Dextromoramide Dihydrocodeine Dipipanone Ethylmorphine Heroin Hydrocodone Hydromorphone Levorphanol Anabolic steroids Clostebol Dehydrochloromethyltestosterone Fluoxymesterone Mesterolone Metenolone Metandienone Methylphenidate Norpseudoephedrine Pemoline Phendimetrazine Phenmetrazine Phentermine Pipradol Prolintane Morphine Oxycodone Oxymorphone Pentazocine Pethidine Phenazocine Piminodine Thebacon Trimeperidine Methyltestosterone Nandrolone Norethandrolone Oxymesterone Stanozolol Testosterone* Sympathomimetic amine stimulants Clorprenaline Isoprenaline Ephedrine Methoxyphenamine Etafedrine Methylephedrine Isoetharine Miscellaneous central nervous system stimulants Amiphenazole Ethamivan Bemegride Leptazol Caffeine** Nikethamide Cropropamide Picrotoxin Crotethamide Strychnine Doxapram * Ratio of total concentration of testosterone to that of epitestosterone in the urine must not exceed 6. ** Concentration in urine must not exceed 15 #g/me 67

arrival of the samples at the laboratory in most cases (The longest time of 25 h occurred in only 1~ of the cases). If it was found that bottle A contained a banned doping substance, the urine from bottle A was reanalyzed. If the same result was obtained, the OCA-MC/IOC-MC was notified and the OCA-MC/IOC-MC notified the athlete and the chief of mission of that athlete's delegation, and they were asked to come to DCC within 24 h to witness the opening of bottle B and subsequent analysis of that specimen. At that time, the athlete could inspect the bag to check whether the chain of custody had been maintained properly. If the athlete had any objections, they were noted and reported to the OCA-MC/IOC-MC. If the bottle B analysis result was identical to the bottle A result, a report was again sent to the OCA-MC/IOC-MC who summoned the athlete and the chief of the mission, coach, or team doctor to a special meeting. During that session an OCA-MC/IOC-MC member explained the laboratory findings. Some athletes admitted to taking a drug without knowing it contained banned substances (e.g. a woman athlete may take a diet pill without knowing it contains norephedrine which is a banned substance). Screening procedures The IOC-MC classified banned substances according to their pharmacological properties (refer to banned drugs lists). The DCC laboratory set up doping analyses methods to cover as many drugs as possible without sacrificing sensitivity and specificity within one procedure. Its screening method consisted of five different procedures; GC, GC/MSD, LC, and TDx were used, and every presumptive positive case was confirmed by GC/MS. Detailed analytical procedures have been reported (4,5,6,7,8) and here the overview of the screening procedures are briefly described. Table II describes analytical equipment the DCC laboratory employed to perform each procedure during the 1986 Asian Games and the 1988 Seoul Olympic Games, and a list of the banned drugs that can be detected by each procedure is given. Procedure I: volatile doping agents. Alkaline extraction of urine by ether, with the etherical layer injected onto a gas chromatograph equipped with a nitrogen specific detector and Doping Classes and Methods Doping classes Stimulants* Narcotics Anabolic Steroids Beta-blockers** Diuretics Doping methods Blood doping Pharmacological, chemical and physical manipulations. Classes of drugs subject to certain restrictions Alcohol Local anaesthetics Corticosteroids t * The definition of a caffeine positive is a urine concentration in excess of 12 t~g/ml. ** Some beta-2 antagonists are permitted in aerosol form. Administration of HCG and other compounds with related activity that lead to an increased rate of production of androgenic steroids is banned. t Cortieosteroids are banned except for topical use (aural, ophtalmological, and dermatological), inhalation theraphy (asthma, allergic rhinitis), and local or intraarticular injections. Banned Drugs in '88 Seoul Olympic Games Stimulants (40) Amfepramone Furfenorex (diethylpropion) Mefenorex Amphetaminil Methoxyphenamine Amiphenazole Methamphetamine Amphetamine Methylephedrine Benzphetamine Methylphenidate Caffeine Morazone Cathine Nikethamide (norpseudoephedrine) Pemoline Chlorphentermine Pentetrazol Clorprenaline (cardiazole) Clobenzorex Phendimetrazine Cocaine Phenmetrazine Cropropamide Phentermine Cortethamide Phenyipropanolamine Dimethamphetamine (norephedrine) Ephedrine Pipradol Etafedrine Prolintane Ethamivan Propylhexedrine Etilamfetamine Pyrovalerone Fencamfamine Strychnine Fenetylline Fenproporex Narcotic analgesics (19) ct-prodine Levorphanol Anileridine Buprenorphine Morphine Codeine Nalbuphine Dextromoramide Pentazocine Dihydrocodeine Pethidine Dipipanone (meperidine) Ethoheptazine Phenazocine Ethylmorphine Trimeperidine Heroin Beta-blockers (9) Acebutolol Nadolol Alprenolol Oxprenolol Atenolol Propranolol Labetalol Sotalol Metoprolol Anabolic steroids (16) Bolasterone Methyltestosterone Boldenone Nandrolone Clostebol Norethandrolone Dehydrochloromethyl- Oxandrolone testosterone Oxymesterone Fluoxymesterone Oxymetholone Mesterolone Stanozolol Methenolone Testosterone Methandienone Diuretics (13) Acetazolamide Diclofenamide Amiloride Ethacrynic acid Benzthiazide Furosemide Bendrofluazide Hydrochlorothiazide Bumetanide Spironolactone Canrenone Triamterene Chiorthalidone 68

Table II. Analytical Equipment Used for Each Procedure Analytical Equipment 1. For screening procedure i: GC (HP 5890), equipped with an automatic injector (HP 7673A) and N-FID, column SE-54, cross-linked, 0.33 tam, 0.2 mm i.d. 2. For screening procedure 11: GC (HP 5890), equipped with a mass selective detector (MSD, HP 5970), column SE-30, cross-linked, 0.33 tam, 0.2 mm i.d. 3. For screening procedure II1: HPLC, HP 1090 with autosampler, diode array detector, ODS column, 10 cm x 4.6 mm i.d., 5 ~m particle 4. For screening procedure IV: For nonconjugated fraction, column SE-54, 17-m length, 0.33 tam, 0.2 mm i.d., GC (HP 5890), MSD (HP 5970). For conjugated fraction, column SE-30, 17-m length, 0.11 tam, 0.2 mm i.d., GC (HP 5890), MSD (HP 5970) 5. For screening procedure V: TDx system from Abbott Laboratories for amphetamine, opiates, cocaine metabolite, benzodiazepines, and barbiturates For confirmational analysis 1. GC/MS (HP 5988A) with electron impact and chemical ionization source. 2. LC/MS (HP 5988) with thermospray interface. Number of units '86 Games '88 Games 3 6 1 2 3 6 1 2 2 4 1 4 1 1 1 1 Banned Drugs Classified According to Detection Procedure Procedure I Stim u/an ts Amfepramone (diethylpropion) Amphetaminil Amiphenazole Amphetamine Benzphetamine Caffeine Cathine (norpseudoephedrine) Chlorphentermine Chlorprenaline Clobenzorex Cropropamide Dimethamphetamine Ephedrine Etafedrine Etilamfetamine Fencarnfamine Fenetylline Fenproporex Narcotic analgesics Alpha-prodine Dextromoramide Dextropropoxyphene Dipipanone Furfenorex Mefenorex Methoxyphenamine Methamphetamine Methylephedrine Methylphenidate Morazone Nikethamide Pentetrazol (cardiazole) Phendimetrazine Phenmetrazine Phentermine Phenylpropanolamine (norephedrine) Pipradol Prolintane Propylhexedrine Strychnine Ethoheptazine Pethidine (meperidine) Procedure II Stimulants Cocaine Narcotic analgesics Anileridine Buprenorphine Codeine Dihydrocodeine Ethylmorphine Heroin Beta-blockers Acebutolol Alprenolol Labetalol Metoprolol Procedure III Diuretics Acetazolamide Amiioride Benzthiazide Bendrofluazide Bumetanide Canrenone Chlorthalidone Procedure IV Free Fraction Bolasterone Dehydrochioromethyltestosterone Fluoxymesterone Ethamivan Levorphanol Morphine Nalbuphine Pentazocine Phenazocine Nadolol Oxprenolol Propranolol Sotalol Dichlorphenamide Ethacrynic acid Furosemide Hydrochlorothiazide Spironolactone Triamterene Metandienone Oxandrolone Stanozolol Beta-blockers Acebutolol Atenolol Conjugated Fraction Bolasterone Boldenone Clostebol Mesterolone Methyltestosterone Nandrolone Norethandrolone Oxymesterone Oxymetholone Testosterone 69

a 5% phenylmethylsilicone capillary column (17 m x 0.2 mm i.d., film thickness 0.33 ~m) was used to screen for stimulants (see reference 4). Procedure lh phenylalkylamines, narcotic analgesics, and beta-blockers. The procedure involves acid hydrolysis, extraction at ph 9.6 with borate buffer, selective derivatization, and injection into a GC/MSD using a cross-linked methylsilicone capillary column (17 m x 0.2 mm i.d., film thickness 0.33 #m) (see reference 5). Procedure III: caffeine, pemoline, diuretics, and corticosteroids. The procedure involves extraction with Sep-Pak C,8 cartridges, elution with ether and methanol, followed by evaporation, dissolving the residue in methanol and injection into an HPLC with an ODS column with gradient elution and a diode-array UV detector (see reference 6). Procedure IV: anabolic steroids. The procedure involves extraction of urine with XAD-2, elution with methanol, separation of nonconjugated steroids from conjugated steroids between buffer and ether, derivatization of nonconjugated steroids without further treatment, and derivatization of conjugated steroids after enzymatic hydrolysis (see reference 7). Procedure for amphetamines, opiates, cocaine metabolites, cannabinoids, barbiturates, and benzodiazepines. To supplement GC and GC/MS data for doping analysis, a fluorescence polarization immunoassay (TDx system of Abbott Laboratories) was used. Methods to analyze amphetamines, opiates, cocaine metabolites, phencyclidine, cannabinoids, barbiturates, and benzodiazepines were available. The TDx system is a homogeneous competitive immunoassay system utilizing fluorescence polarization immunoassay (FPIA) methodology and computerized automation with bar coded reagent packs. The system can perform assays of therapeutic drugs, hormones, clinical chemistries, proteins, and abused drugs and their metabolites in serum or urine. Positive cases Positive results were reported to the Medical Commission only when the following criteria were fulfilled: (1) Identical in retention times and matching mass spectra with the known dope agents in the screening procedure were obtained, and Table III. Caffeine Concentration of Doping Samples from the 1986 Asian Games and 1988 Olympic Games Distribution (%) Concentration (mgll) '86 Games '88 Games <0.01 311 (51.5%) 612 (38.2%) 0.01-1.000 204 (34.9%) 427 (26.7%) 1.000-2.000 52 (8.9%) 296 (18,5%) 2.000-3.000 14 (2.4%) 124 (7.7%) 3.000-4.000 4 (0.7%) 64 (4.0%) 4.000-5.000 0 30 (1.9%) 5.000-6.000 0 23 (1.4%) 6.000-7.000 0 8 (0.5%) 7.000-8.000 0 7 (0.4%) 8.000-9.000 0 4 (02%) 9.000-10.000 0 2 (0.1%) 10.000-11.000 0 2 (0.1%) 11.000-12.000 0 0 greater than 12.000 0 2 (0.1%) Tom/ 585 1,601 (2) reextraction from the sample bottle, repetition of the analysis, and reidentification of retention times and mass spectra with the reference compound were performed. Sanction The ideal way to curb drug abuse is through education. When athletes realize the effects of doping substances, many will not use them. Some athletes use drugs without knowing that they are banned substances. For those who use drugs intentionally though, the most effective way to curb use is through detection and punishment of athletes who violate the rules. On the occasion of the 75th Anniversary of the International Amateur Athletic Federation, August 1987, in Rome, the congress adopted the following ten-point proposal that will considerably advance the continued IAAF campaign for prevention of doping abuse: (1) Increased penalties for doping offenders. For offences involving ephedrine or its derivatives, athletes are banned from competition as follows: First offence: for a minimum of three months from the date of the offence. Secoad offence: for two years from the date of the offence. Third offence: for life. For offences involving other substances on the list of banned classes: First offence: for two years from the date of the offence. Second offence: for life. (2) Doping control laboratories to be established on every continent. (3) More doping tests to be conducted at major games and championships. (4) Obligation of all national federations to accept, when required, IAAF antidoping collection teams at their national championships. (5) Obligation of all national federations to test at national competitions and during the training periods. (6) Top world class athletes to endorse the campaign through the IAAF Athletes Subcommittee. (7) Clothing contracts to be immediately cancelled for athletes found guilty of doping. (8) Vigorous young people's Anti-Doping Campaign to be continued through the publication Save the Future, Save Yourself. This book, which is sponsored by the International Athletic Foundation, will be made available in different languages. (9) Continuing support of Medical Symposia, particularly those that give emphasis to antidoping education. (10) IAAF to continue providing of antidoping kits to all national federations. At their regular meeting, August 1987 in Moscow, USSR, the IOC-MC took a similar position and, based on the experience of more than 20 years in doping control activities, differentiated between "deliberate" and "inadvertent" use of doping substances. The IOC-MC decided to sanction for deliberate doping, e.g. anabolic steroids, amphetamine type stimulants, caffeine, cocaine, narcotic drugs, and designer drugs, three years for the first offence and life ban for the second offence. For inadvertent use of banned drugs, e.g. ephedrine and codeine, three months for the first offence, two years for the second offence, and life ban for the third offence. Caffeine concentration The caffeine concentration was monitored and the results are summarized in Table III. The caffeine concentration of the athletes tested in the 10th Asian Games are lower compared to 70

Journal of Analytical Toxicology, Vol, 14, March/April 1990 the results of the 1984 Sarajevo Winter Olympic Games and 1984 Los Angeles Olympic Games (9). This trend justified the IOC-MC decision to lower the caffeine concentration limit from 15 mg/l at the 1984 Games to 12 mg/l at the 1988 Games. Testosterone-epitestosterone ratio Testosterone is an endogenous anabolic steroid and is also a banned substance. The IOC-MC rule regards testosterone/ epitestosterone ratio in urine higher than six to be a positive doping case. The testosterone-epitestosterone ratios were monitored during the Asian Games and the highest observed value was 4.14. The calculated arithmetic mean was 0.76 and the median 0.46; these two parameters are lower than those of Caucasian races (mean 1.1 to 1.7, depending on the population, and median 0.92). Another interesting observation is that the concentration of testosterone-glucuronide is relatively low (mean 23.6 ng/ml, N = 435 samples), but the epitestosterone concentration seems to be in the same range with that of Caucasians (mean 36.7 ng/ml). A detailed study of steroid profiles of Asian races will be published later (9,10). Human chorionic gonadotropin (HCG) test There was a widely spread report that some athletes were using HCG, anticipating a natural increase in the body's testosterone. If that were the case and the level of endogenous testosterone is increased, then determination of the testosterone/epitestosterone ratio cannot be used to check doping practices. It was therefore decided to measure HCG in urine. There are many commercial diagnostic kits available for pregnancy testing but no kit for quantitative measurement of HCG in urine. DCC developed an enzyme immunoassay (EIA) kit which uses a monoclonal antibody reaction. The high specificity and consistent affinity of the monoclonal antibody gives the assay good accuracy and precision (CV less than 8o70). Cross-reactivity studies indicated that this method measures only intact HCG with almost no response to its tx - or/~-subunits (less than 2O7o) or similar glycoproteins such as human leutenizing hormone (5.7o70), thyroid stimulating hormone (0o70), and follicle stimulating hormone (0070). The detection limit of the assay that could be consistently distinguished from its background is 0.50 miu/ml (1 l, 12). This kit was compared with other commer- Table IV. Density Distribution of Doping Samples from the 1988 Olympic Games Number Density of samples Percent (%) less than 1.000 0 0.00 1,000-1.005 6 0.37 1.005-1.010 70 4.37 1.010-1.015 242 15.12 1,015-1.020 101 6.31 1.020-1.025 462 28.86 1.025-1.030 219 13.68 1.030-1,035 496 30.98 1.035-1.040 3 0.19 1.040-1.045 0 0.00 1.045-1.050 0 0.00 1.050-1.055 1 0.06 1.055-1.060 0 0.00 greater than 1.060 0 0.00 Uncountable 1 0.06 Total 1601 100,0 cial kits (for quantitative measurement of HCG in blood) Amerlex-M B-HCG RIA kit (Amersham, England) and Tandem-R HCG kit (Hybritech). Its correlation coefficient was r = 0.97 (with Amerlex kit) and r = 1.00 (with Tandem kit). Normal value of HCG of urine of males and nonpregnant females is 0-20 mlu/ml. For the '88 Olympic Games, all male specimens had HCG values lower than 30 mlu/ml and all female specimens had HCG values lower than 30 mlu/ml except for 4 samples of those (one had 3700 mlu/ml and another had 4200 miu/ml which should be regarded as coming from pregnant competitors). Tetrshydrocannablnol (THC) test Marijuana smoking is the most frequent form of illicit drug use in many parts of the world and the consequences of marijuana use can be serious. It was decided to test for Ag-THC-9 - carboxylic acid (carboxy-thc) during the '88 Olympic Games using the TDx assay method (Abbott Laboratories) for screening and GC/MS for confirmation. There were 4 positive cases of THC (all cases were confirmed by GC/MS) out of 1601 urine samples tested. Corticosteroid test The use of corticosteroids (naturally occurring or synthetic) is banned except for topical use, inhalational therapy, and local or intraarticular injection. These corticosteroids were screened by HPLC/DAD and confirmed by a thermospray LC/MS technique. During the '88 Olympic Games, 1601 urine samples were tested for corticosteroids. In addition, the ratio of cortisol to cortisone concentrations was measured in each urine sample; its mean value was 0.64. This corresponded to the mean (0.64) obtained from 598 urine samples tested during the '86 Asian Games. Density and ph During the '88 Olympic Games the density and ph for each specimen were measured with test strips (MD-Spezial fur steinstrager of Dr. Madaus GmbH & Co.) and the results are summarized in Tables 1V and V. The urine density ranged from 1.005 to 1.040 with a mean of 1.021. No correlation of density with use of diuretics was found. The ph values of most specimens were between 5.0 and 8.0 with a mean value of 5.8. Table V. ph Distribution of Doping Samples from the 1988 Olympic Games Number ph of samples Percent (%) less than 5.0 0 0.00 5.0-5.5 328 20.49 5.5-6.0 534 33.35 6.0-6.5 547 34.17 6.5-7.0 94 5.87 7.0-7.5 56 3.50 7.5-8.0 24 1.50 8.0-8.5 10 0.62 8,5-9,0 7 0.44 9.0-9.5 9.5-10.0 0 0 0.00 0.00 greater than 10.0 0 0.00 Uncountable 1 0.06 Total 1601 100.0 71

Summary '89 Asian Games At the 10th Asian Games 1986, Seoul, 585 samples were analyzed in 15 days, corresponding to an average daily capacity of 40 samples. Stimulants, narcotics, and anabolic steroids were screened in all samples. For the shooting events, beta-blockers were tested, and for the equestrian events, blood and urine samples of the horses were analyzed for sedatives and nonsteroidal antiinflammatory drugs. The results were reported daily to the Medical Commission of OCA within 24 hours after the arrival of the last batch of samples in the laboratory. 20 samples were reported, to contain banned substances; 6 ephedrines, 1 beta-blocker, and 12 anabolic steroids were found in the screening procedures and confirmed by additional analytical tests. The final conclusions were made after evaluation of the chromatographic and mass spectral data. '88 Seoul Olympic Games In continuation of its antidoping policy, the IOC-MC initiated doping tests for the 1988 Seoul Olympic Games. DCC analyzed 1601 samples in 15 days with the highest number of tests being 160 samples on one day. Stimulants, narcotics, diuretics, betablockers, anabolic steroids, and human chorionic hormone gonadotrophin were tested for all samples. Probenecid (against pharmacological manipulation) and corticosteroids (against banned substances subject to certain restriction) were tested for all samples. Barbiturates and benzodiazepines were tested for requested events. Cannabinoids were also tested for all samples. Urine samples of the horses for equesterian events were analyzed for sedatives and nonsteroidal antiinflammatory drugs. The results were reported daily to the IOC-MC within 24 hours without exception. Stimulants (caffeine, pemoline), betablockers (nadolol, propranolol), diuretics (furosemide), and anabolic steroids (stanazolol) were among the positive findings. Acknowledgment We deeply appreciate the advice and assistance of IOC-MC members, especially the Chairman of the Commission Prince de Merode and the Chairman of Subcommission "Doping and Biochemistry of Sport" Dr. Manfred Donike. Without their continuous encouragement and advice, it would not have been possible to accomplish this work. Many individuals in the KAIST, SLOOC, KOC, and MOST contributed their commitment to the success of this work. Hewlett-Packard in the U.S.A. and their distributor in Korea, Youngln Sci. Co., and Abbott Laboratories Diagnostic Division did their best to ensure the success of this event. Many pharmaceutical companies throughout the world donated authentic standard materials. To name a few, I truly appreciate the following people's efforts in making the program successful. Dr. Hoagy Kim and Dr. Sungduk Park of MOST, Dr. Byungyun Cho of SLOOC, Dr. Kim and Mr. Changsin Choi of MOS, Mr. Mike Muller and Mr. Bud Bromley of Hewlett-Packard, Mr. Sungil Lee and Mr. Youngho Cho of Youngln Sci., Ms. Victoria Bannister and Ms. Sally Stewart of Abbott Laboratories. Most of all, without following staff's excellent analytical skills and techniques and full dedication to this cause, this endeavor would not have been possible; HoSang Shin, HeaKyung Kang, YunSuk Oh, YunJe Kim, JongKi Hong, MinKyung Lee, TaeHyun Lee, MiSook Park, SeungUn Myung, JaWon Suh, HeeSoo Pyo, Meesook Kim, SeiOk Park, OhSeung Kwon, JongSoon Yang, JeongAi Lee, MyungWhan Chi, BoKyung Kang, HeangKee Paek, TaeWook Kim, and GheeDong Eom. We also appreciate the efforts of the staff from Dr. M. Donike's laboratory: Dr. Schaenzer, Dr. D. Mandel, Messrs. Sigmund, Kraft, and Geyer for their assistance during 1986 Asian Games. References 1. B. Goldman. Death in the Locker Room, Steroids in Sports, 1984, BL Publisher, U.S.A. 2. A. Dirix. Dope Control at the Olympic Games. In Proceedings of International Symposium on Drug Abuse in Sports. September 12, 1988, Seoul, Korea. 3. Don H. Catli0, R. Craig Kammerer, Caroline K. Hatton, Michael H. Sereka, and James L. Merdink. Analytical chemistry at the Games of the XXlllrd Olympiad in Los Angeles, 1984. Clin. Chem. 4. 33:319-27 (1987). Dong-Seok Lho, Manfred Donike, Ho-Sang Shin, Bo-Kyung Kang, and Jongsei Park. Systematic analysis of stimulants and narcotic analgesics by gas chromatography with nitrogen specific detection and mass spectrometry. J. Anal Toxicol. 14:73-76 (1990). 5. Dong-Seok Lho, Manfred Donike, Jong-Ki Hong, Heang-Kee Paek, Jeong-Ae Lee, and Jongsei Park. Determination of phenolalkylamines, narcotic analgesics and beta-bl0ckers by gas chromatography/mass spectroscopy. J. Anal ToxicoL 14:77-83 (1990). 6. Song-Ja Park, Hee-Soo Pyo, Yun-Je Kim, Mi-Sook Kim, and Jongsei Park. Systematic analysis of diuretic doping agents by HpLC screening and GC/MS confirmation. J. Anal. ToxicoL 14: 84-90 (!990). 7. BongChul Chung, Hea-Young P. Choo, Manfred Donike, TaeWook Kim, KheeDong Eom, OhSeung Kwon, Jawon Suh, Joongsoon Yang, and Jongsei Park. Analysis of anabolic steroids using GC/MS with selected ion monitoring. J. Anal ToxicoL 14:91-95 8. 9. (1990). Song-Ja Park, Yun-Je Kim, Hee-Soo Pyo, and Jongsei Park. Analysis of corticosteroids in urine by HPLC and thermospray LCIMS. J. Anal. Toxicol. 14:102-108 (1990). Report on the Doping Analyses Performed during the 10th Asian Games, 1989 Seoul 20th of September to 5th of October. Seoul Asian Games Organizing Committee-Medical Commission, 1987. 10. Jongsei Park. Doping test report of 10th Asian games in Seoul 1. 032. J. Sports Med. Phys. Fitn. (1989). 11. S. Choi, H. Kang, D. Yoon, K. Choi, M. Choi, 1. Choe, T. Chung. Production and characterization of monoclonal antibodies specific to human chorionic gonadotropin and its subunits. Korean Biochem. J. 222:202-208 (1989). 12. M. Choi, H. Kang, J. Lee, I. Choe, T. Chung. Simple multi-enzyme immunoassay for the simultaneous measurement of whole molecule and free f~-subunit choriogonadotropin in the serum of trophoblastic disease. Future publication. Manuscript received May 17, 1989; revision received January 9, 1990. 72