1. Introdução
4.2 Método Confirmatório
4.3.2 Estudo comportamental
Após minuciosa análise quantitativa, qualitativa, interpretação global de cada exame e, subseqüentemente, a análise comparativa dos exames de cada voluntário que ingeriu pseudoefedrina em relação àqueles que ingeriram placebo, foi verificado que todos aqueles que fizeram uso do medicamento sofreram alterações em seus níveis de tônus vital, agressividade e emotividade:
• tônus vital: os níveis endógenos e reacionais subiram em níveis consideráveis e, ao final do teste, evidenciaram uma tendência à fadiga, uma vez que sofreram quedas bruscas em seus escores.
• agressividade: os níveis endógenos e reacionais diminuíram notadamente e mantiveram seus escores do início ao fim do teste.
• emotividade: os níveis endógenos e reacionais subiram de maneira expressiva e mais evidente em relação às duas mensurações anteriores. Tal emotividade deve ser compreendida não na ordem de vivência de sentimentos, mas como a capacidade do sujeito de sentir com profundidade as impressões e, quando percebidas intensamente, ocasionam o choque emotivo que desencadeia uma reação global, tanto orgânica quanto psíquica.
Assim, a partir da análise conjunta desses dados, pode-se inferir que a pseudoefedrina promove um aumento importante do tônus postural do indivíduo e tem sua ação potencializada graças à captação dos níveis de agressividade (por isso seus escores diminuídos) e o aumento considerável dos níveis de emotividade, que dão ao indivíduo mais “vitalidade” para a ação. Entretanto, após essa “explosão energética”, tem-se uma queda rápida desse tônus e subseqüente fadiga.
5 Conclusões
Em relação ao método de screening, baseado em espectrometria de massas e desenvolvido nesse trabalho, pode-se dizer que o mesmo é uma boa opção para triagem sistemática em análises de controle de dopagem, pois atende aos principais requisitos. O tempo de análise é curto (aproximadamente 2 minutos), o que torna possível a sua aplicação a uma grande quantidade de amostra, como acontece em procedimentos de rotina. A preparação das amostras limita-se a um simples processo de diluição, o que reduz consideravelmente, não apenas o tempo gasto nessa etapa como também a quantidade de solventes a serem descartados. E o mais importante, esse método apresentou uma boa confiabilidade (exceto para o par de isômeros norefedrina/catina), haja vista a baixa incidência de resultados “falso- positivos” e “falso-negativos”. Por outro lado, a utilização da espectrometria de massas como técnica para screening ainda está longe de se tornar uma realidade, porque os bons equipamentos ainda apresentam um custo elevado.
Em relação ao método confirmatório baseado em cromatografia a gás, acoplada à espectrometria de massas, conclui-se que o mesmo consiste em uma ótima opção para análises de controle de dopagem. As etapas de preparação de amostra foram bastante simples. A extração em fase sólida (EFS) é eficiente, rápida (necessita de apenas alguns minutos), dispensa muitas etapas (evitando, assim, a manipulação excessiva das amostras), e utiliza pequena quantidade de solvente, reduzindo a quantidade de material a ser descartado. A derivatização com anidrido acético em piridina, além de eficiente, apresenta custo reduzido, por utilizar reagentes em grau analítico, que podem ser encontrados na maioria dos laboratórios de pesquisa e análises de rotina. A análise, por sua vez, não é um processo considerado rápido para cromatografia. Entretanto, o método desenvolvido apresentou elevada sensibilidade, além de bons índices de precisão e recuperação. Embora não tenha sido feito qualquer estudo de seletividade, pode-se dizer que, nas condições de trabalho em que foi desenvolvido (utilizando pool de urina e analisando em modo SIM), o mesmo foi bastante seletivo, pois apresentou pouco ou quase nenhum interferente.
Finalizando, pode-ser dizer que tanto o método de screening quanto o método confirmatório que foram desenvolvidos nesse trabalho se equiparam aqueles apresentados recentemente na literatura.
6 Referências Bibliográficas
ABERL, F; VANDINE, R. Saliva and sweat testing with drugwipe: A review. Drugs of Abuse, conferência, p. 161 – 175, 2005.
AJINOMOTO CO., INC. (Tóquio, JP). Tadashi Takemoto e Hideo Takeda. Method for Preparing Amino Acid Esters. EP 0 544 205 A2 n. 92119898.2, 28 nov. 1991, 02 de jun. 1993.
ANDERSON, C. Presumptive and confirmatory drug tests. Journal of Chemical Education, v. 82, n. 12, p. 1809 – 1810, 2005
ASGHAR, S. J. et al. Relationship of plasma amphetamine levels to physiological, subjective, cognitive and biochemical measures in healthy volunteers. Human Psychopharmacology, v. 18, n. 4, p. 291 – 299, 2003
ASSOCIAÇÃO BRASILEIRA DE ESTUDOS E COMBATE DO DOPING, Manual Prático de Controle Antidoping e Alternativas Naturais. 2.ed. Associação Brasileira de Estudos e Combate do Doping, 2002, 72p.
AVOIS, L. et al. Central nervous system stimulants and sport practice. British Journal of Sport Medicine, v. 40, Suppl 1, i 16 – 20, 2006
BAKHTIAR, R. Letter: complexes of amino-(6-monodeoxy-6-mono)-β-cyclodextrin probed by electrospray ionization mass spectrometry. European Mass Spectrometry, Cinchester, v. 5, n. 1, p. 1 – 5, 1999
BALAKRISHNAN, V. K.; TERRY, K. A.; TOITO, J. Determination of sulfonamide antibiotics in wastewater: A comparison of solid phase microextraction and solid phase extraction methods. Journal of Chromatography A, v. 1131, n. 1 – 2, p. 1 – 10, 2006
BALDACCI, A. et al. Determination of γ-hydroxybutyric acid in human urine by capillary electrophoresis with indirect UV detection and confirmation with electrospray ionization ion-trap mass spectrometry. Journal of Chromatography A, v. 990, n. 1 - 2, p. 99 – 110, 2003
BASKIN L. B.; MORGAN D. L. Drugs detected in patients suspected of acute intoxication. Texas Medicine, v. 93, n. 9, p. 50 – 58, 1997
BATTU, C. et al. Screening procedure for 21 amphetamine-related compounds in urine using solid-phase microextraction and gas chromatography-mass spectrometry. Journal of Chromatographic Science, v. 36, n. 1, p. 1 – 7, 1998
BECKETT, A. H.; TUCKER, G. T.; MOFFAT, A. C. Routine detection and identification in urine of stimulants and other drugs, some which may be used to modify performance in sport. Journal of Pharmacy and Pharmacology, v. 19. n. 5, p. 273 – 294, 1967
BELSON, M. G.; SIMON, H. K. Utility of comprehensive toxicologic screens in children. The American Journal of Emergency Medicine, v. 17, n. 3, p. 221 – 224, 1999
BENEZRA S. A., MCRAE J. W., Analytical Profiles of Drug Substances. New York: Academic Press, 1979; 489 p.
BENTLEY K. W. beta-Phenylethylamines and the isoquinoline alkaloids. Natural Product Reports, v. 20, n. 3. p. 342-365, junho, 2003
BERGO, P. L. S. Relatório Final do Treinamento em Docência Química, 2005, 29f. (Treinamento em Docência Química – Química Analítica). Departamento de Química, Universidade Federal de Minas Gerais, Belo Horizonte, 2005
BEYER, J.; EHLERS, D.; MAURER, H. H. Abuse of nutmeg (Myristica fragrans Houtt): Studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry. Therapeutic Drug Monitoring, v. 28, n. 4, p. 568 – 575, 2006
BLAU, K.; HERMANN F.; HALKET, J. M. Handbook of derivatives for chromatography. 2ed. Chichester : John Wiley & Sons, 1993, 396p.
BOATTO, G. et al. Determination of amphetamine-derived designer drugs in human urine by SPE extraction and capillary electrophoresis with mass spectrometry detection. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, v. 814, n. 1, p. 93 – 98, 2005
BOLAND, D. M.et al. Fatality Due to Acute α -Methyltryptamine Intoxication. Journal of Analytical Toxicology, v. 29, n. 5, p. 394 – 398, 2005
BOUCHARD, R;. WEBER, A. R.; GEIGER, J. D. Informed decision-making on sympathomimetic use in sport and health. Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine, v. 12, n. 4, p. 209 – 224, 2002
BUDZINSKI, H. et al. Analysis of hormonal steroids in fish plasma and bile by coupling solid - phase extraction to GC / MS. Analytical and Bioanalytical Chemistry, v. 386, n. 5, p. 1429 – 1439, 2006
BURROWS, D. L. et al. The distribution of sevoflurane in a sevoflurane induced death. Journal of Forensic Sciences, v. 49, n. 2, p. 394 – 397, 2004
CAPRINO, L.; BRAGANO, MC.; BOTRE, F. Herbal supplements in sports: use and abuse. Annali dell'Istituto superiore di sanita, v. 41, n. 1, p. 35 – 38, 2005
CARABIAS-MARTINEZ, R.et al. Pressurized liquid extraction in the analysis of food and biological samples. Journal of Chromatography A, v. 1089, n. 1 – 2, p. 1 – 17, 2005
CATLIN, D. H. et al. Analytical chemistry at the games of the XXIIIrd Olympiad in Los Angeles, 1984. Clinical Chemistry, v. 33, n. 2, p. 319 – 327, 1987
CENTRE FOR ADDICTION AND MENTAL HEALTH Do you know… Amphetamines. Toronto. Centre for Addiction and Mental Health, 2004. 2p.
CHEN, T. et al. Evidence for the Involvement of Dopamine D1 and D2 Receptors in Mediating the Decrease of Food Intake during Repeated Treatment with Amphetamine. Journal of Biomedical Science, v. 8, n. 6, p. 462 – 466, 2001
CHIA, D. T.; GERE, J. A. Rapid drug screening using Toxi-Lab extraction followed by capillary gas chromatography/mass spectroscopy. Clinical Biochemistry, v. 20, n. 5, p. 303 – 306, 1987
CITOVA, I.; SLADKOVSKY, R.; SOLICH, P. Analysis of phenolic acids as chloroformate derivatives using solid phase microextraction-gas chromatography. Analytica Chimica Acta, v. 573 – 574, n. N1 – N2, p. 234 – 241, 2006
CLARKSON, P. M.; THOMPSON, H. S. Drugs and sport. Research findings and limitations. Sports Medicine, v. 24, n. 6, p. 366 – 384, 1997
CODY, J. T. et al. Amphetamine, clobenzorex, and 4-hydroxyclobenzorex levels following multidose administration of clobenzorex. Journal of Analytical Toxicology, Niles, v. 25, n. 3, p. 158 – 165, 2001
CONFEDERAÇÃO BRASILEIRA DE FUTEBOL. Regulamento de Controle de Dopagem. Rio de Janeiro: Confederação Brasileira de Futebol, 2006, 40p.
CONLEE, R. K. Cocaine. Performance-Enhancing Substances in Sport and Exercise, p. 279 – 288, 2002
CONSELHO DA EUROPA. La charte européenne contre lê dopage dans le sport. Exposição dos Motivos. Lisboa: Direcção Geral de Desportos, 1985, 40p.
COTTON, S. Metahmphetamine (and its isomers). Disponível em <http://www.chm.bris.ac.uk/motm/methamphetamine/methc.htm>, acesso em 30/12/2006
DABISCH, P.; LILES, J. T.; KADOWITZ, P. J. Effect of inhibition of nitric oxide synthase on the vasopressor response to ephedrine. Canadian Journal of Physiology and Pharmacology, v. 81, n. 10, p. 966 – 971, 2003
DAHLEN, J.; VON ECKARDSTEIN, S. Development of a capillary zone electrophoresis method including a factorial design and simplex optimization for analysis of amphetamine, amphetamine analogues, cocaine, and heroin. Forensic Science International, v. 157, n. 2 – 3, p. 93 – 105, 2006
DALY, J. W.; BUTTS-LAMB, P.; PADGETT, W. Subclasses of adenosine receptors in the central nervous system: interaction with caffeine and related methylxanthines. Cellular and Molecular Neurobiology, v. 3, n. 1, p. 69 – 80, 1983
DE HOFFMANN, E.; STOOBANT, V. Mass Espectrometry: Principles and Applications. 2.ed. New York: John Wiley & Sons, LTD. 2002, 407p.
DEF 2006/2007 – Dicionário de especialidades farmacêuticas. 35ed. Publicações Biomédicas, 2006, 898p.
DEVENTER K.; VAN EENOO, P.; DELBEKE, F. T. Screening for amphetamine and amphetamine-type drugs in doping analysis by liquid chromatography/mass spectrometry. Rapid Communications in Mass Spectrometry, v. 20, n. 5, p. 877 – 882, 2006.
DI PIETRA, A. M. Analysis of amphetamine and congeners in illicit samples by liquid chromatography and capillary electrophoresis. Journal of Analytical Toxicology, v. 25, n. 2, p. 99 – 105, 2001
DIMETAPP: Gel cápsulas. Responsável técnico: Ruy M. Yoshinaga. São Paulo: Whitehall, 2006. Bula de Remédio.
DODD, S. L.; HERB, R. A.; POWE, S. K. Caffeine and exercise performance – an update. Sports Medicine, v. 15, n. 11, p. 14 – 23, 1993
DRESEN, S.; KEMPF, J.; WEINMANN, W. Electrospray-ionization MS/MS library of drugs as database for method development and drug identification. Forensic Science International, v. 161, n. 2 – 3, p. 86 – 91, 2006
DUMASIA, M. C. Identification of some N-hydroxylated metabolites of (±)-3,4- methylenedioxymethamphetamine in horse urine by gas chromatography-mass spectrometry. Xenobiotica, v. 33, n. 10, p. 1013 – 1025, 2003
EICHHORST, J. et al. Urinary screening for methylphenidate (Ritalin) abuse: a comparision of liquid chromatography-tandem mass spectrometry, gas chromatography- mass spectrometry, and immunoassay methods. Clinical Biochemistry, v. 37, n. 3, p. 175 – 183, 2004
EL-HAJ, B. M. et al. The use of cyclohexanone as a “derivatizing” reagent for the GC-MS detection of amphetamines and ephedrines in seizures and the urine. Forensic Science International, v. 135, n. 1, p. 16 – 26, 2003
ENSSLIN, H. K.; KOVAR, K.; MAURER, H. H. Toxicological detection of the designer drug 3,4-methylenedioxyethylamphetamine (MDE, “Eve”) and its metabolites in urine by gas chromatography – mass spectrometry and fluorescence polarization immunoassay. Journal of Chromatography B, v. 683, p. 189 – 197, 1996
EVERITT, B. S., LANDAU, S., LEESE, M. Cluster Analysis. 4.ed. New York: Oxford University Press, Inc., 2001, 248p.
EWALD, A. H.; FRITSCHI, G.; MAURER, H. H. Designer drug 2,4,5- trimethoxyamphetamine (TMA-2): studies on its metabolism and toxicological detection in rat urine using gas chromatographic/mass spectrometric techniques. Journal of Mass Spectrometry, v. 41, n. 9, p. 1140 – 1148, 2006
FORSDAHL G., GMEINER G., Investigation of the silylation of ephedrines using N- methyl-N-trimethylsilyl-trifluoroacetamide. Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, v. 811, n.2, p. 201-208, novembro, 2004
FOYE, W. O.; LEMKE, T. L.; WILLIAMS, D. A., Principles of Medicinal Chemistry. 4.ed. Baltimore: Williams & Wilkins, 1995. 995p.
FRISON, G. et al. Gas chromatography/mass spectrometry determination of amphetamine -related drugs and ephedrines in plasma, urine and hair samples after derivatization with 2,2,2-trichloroethyl chloroformate. Rapid Communications in Mass Spectrometry, Indianápolis, v. 19, n. 7, p. 919 – 927, 2005
FUCCI, N. et al. An evaluation of the Cozart RapiScan system as an on-site screening tool for drugs of abuse in a non-conventional biological matrix : vitreous humor. Forensic Science International, v. 156, n. 2 – 3, p. 102 – 105, 2006
FUH, M.; WU, T.; LIN, T. Determination of amphetamine and methamphetamine in urine by solid phase extraction and ion-pair liquid chromatography-electrospray-tandem mass spectrometry. Talanta, v. 68, n. 3, p. 987 – 991, 2006
GAILLARD, Y.; VAYSSETTE, F.; PÉPIN, G. Compared interest between hair analysis and urinalysis in doping controls. Results for amphetamines, corticosteroids and anaboli steroids in racing cyclists. Forensic Science International, v. 107, p. 361 – 379, 2000
GAMBELUNGHE, C. et al. Hair analysis by GC/MS/MS to verify abuse of drugs Journal of Applied Toxicology, v. 25, n. 3, p. 205 – 211, 2005
Chimica Acta, 366, n. 1 – 2, p. 101 – 111, 2006
GENTILI, S.; CORNETTA, M.; MACCHIA, T. Rapid screening procedure based on headspace solid-phase microextraction and gas chromatography-mass spectrometry for the detection of many recreational drugs in hair. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, v. 801, n. 2, p. 289 – 296, 2004
GEORGE, A. J. Central nervous system stimulants. Bailiere’s best practice & research. Clinical Endocrinology & Metabolism, v. 14, n. 1, p. 79 – 88, 2000
GEORGE, A. J. CNS stimulants. In MOTTRAM, D.R. Drugs in Sport, 2 ed, London: E. and F. Spon, 1996, Capítulo 4, p 86 – 112
GOLDMAN, B. Death in the Locker Room: Drugs & Sports. London: Century Publishing, 1992
GRAHAM, T. E. Caffeine and exercise: metabolism, endurance and performance. Sports Medicine, v. 31, n. 11, p. 785 – 807, 2001
GRENIER-LOUTALOT, M. Doping control in sports. Actualite Chimique, n. 11 – 12, p. 3 – 7, 1998
GUNNAR, T.; ARINIEMI, K.; LILLSUNDE, P. Validated toxicological determination of 30 drugs of abuse as optimized derivatives in oral fluid by long column fast gas chromatography/electron impact mass spectrometry. Journal of Mass Spectrometry, v. 40, n. 6, p. 739 – 753, 2005
HANG, S. et al.Enantiomeric determination of ephedrines and norephedrines by chiral derivatization gas chromatography -mass spectrometry approaches. Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences, v. 825, n. 1, p. 88 – 95, 2005
HARTMANN, C. et al. Validation of bioanalytical chromatographic methods. Journal of Pharmaceutical and Biomedical Analysis, v. 17, p. 193 – 218, 1998
HERRIN, G. L.; MCCURDY, H. H.; WALL, W. H. Investigation of an LC-MS-MS (QTrap) method for the rapid screening and identification of drugs in postmortem toxicology whole blood samples. Journal of Analytical Toxicology, v. 29, n. 7, p. 599 – 606, 2005
HIDVEGI, E. et al. GC - MS determination of amphetamines in serum using on-line trifluoroacetylation. Forensic Science International, v. 161, n. 2 – 3, p. 119 – 123, 2006
HINO, Y. et al. Performance of immunoassays in screening for opiates, cannabinoids and amphetamines in post-mortem blood. Forensic Science International, v. 131, n. 2 – 3, p.
HODOBA, D. et al. Pharmacology of modafinil – the first experience in the treatment of hypersommia in narcoleptics. Periodicum Biologorum, v. 107, n. 2, p. 195 – 199, 2005
HOLLER, J. M. et al. Quantitative and Isomeric Determination of Amphetamine and Methamphetamine from Urine using a Nonprotic Elution Solvent and R(-)-α -Methoxy-α- Trifluoromethylphenylacetic Acid Chloride Derivatization. Journal of Analytical Toxicology, v. 29, n. 7, p. 652 – 657, 2005
HUANG, M.; LIU, C.; HUANG, S. One step and highly sensitive headspace solid-phase microextraction sample preparation approach for the analysis of methamphetamine and amphetamine in human urine. Analyst, v. 127, n. 9, p. 1203 – 1206, 2002
HUANG, Z.; ZHANG, S. Confirmation of amphetamine, methamphetamine, MDA and MDMA in urine samples using disk solid-phase extraction and gas chromatography-mass spectrometry after immunoassay screening. Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences, v. 792, n. 2, p. 241 – 247, 2003
HUDSON, J. C.; MALCOLM, M. J.; GOLIN, M. Advancements in forensic toxicology. Chemistry in Australia, v. 66, n. 11, p. 28 – 31, 1999
HUDSON, J.C.; GOLIN, M.; MALCOLM, M. Capillary zone electrophoresis in a comprehensive screen for basic drugs in whole blood. Journal - Canadian Society of Forensic Science, v. 28, n. 2, p. 137 – 152, 1995
HUESTIS, M. A.; SMITH, M. L. Modern analytical technologies for the detection of drug abuse and doping. Drug Discovery Today: Technologies, v. 3, n. 1, p. 49 – 57, 2006
HUWYLER, J.; GUT, J. Single-step organic extraction of leukotrienes and related compounds and their simultaneous analysis by high-performance liquid chromatography. Analytical Biochemistry, v. 188, n. 2, p. 374 – 382, 1990
HYOETYLAEINEN, T.; SIREN, H.; RIEKKOLA, M. Determination of morphine analogs, caffeine and amphetamine in biological fluids by capillary electrophoresis with the marker technique. Journal of Chromatography A, v. 735, n. 1 – 2, p. 439 – 447, 1996
INABA, B. S.; COHEN, W. E., Drogas: Estimulantes, Depressores, Alucinógenos: Efeitos Físicos e Mentais das Drogas Psicoativas.1.ed. Rio de Janeiro: Jorge Zahar Editor Ltda., 1991. 255p.
INTERNATIONAL OLYMPIC COMMITTEE MEDICAL COMISSION. Olympic Movement Anti-Doping Code. Lausanne: IOC 1999
INTERNATIONAL OLYMPIC COMMITTEE. Factsheet: The fight against doping and promotion of athletes’ health. Dezembro, 2005, disponível em < http://www.olympic.org>, acesso em 29/12/2006
ISHIDA, T. et al. Rapid Screening for and Simultaneous Semiquantitative Analysis of Thirty Abused Drugs in Human Urine Samples Using Gas Chromatography-Mass Spectrometry. Journal of Analytical Toxicology, v. 30, n. 7, p. 468 – 477, 2006
IVY, J. L.; COSTILL, D. L.; FINK, W. J. Influence of caffeine and carbohydrate feedings on endurance performance. Medicine and Science in Sports, v. 11, p. 6 – 11, novembro, 1979
JAEGER, M. Sudden death during sport activities. How ca the incidence be reduced? Annales de Cardiologie et D’Angeologie, v. 39, n. 10, p. 565 – 570, 1990
JAIN, N. C.; BUDD, R. D.; SNEATH, T. C. Rapid mass screening and conformation of urinary amphetamine and methamphetamine by gas chromatography. Clinical Toxicology, v. 8, n. 2, p. 211 – 224, 1975
JANES, K. A., YAFFE, M. B. Data-driven modeling of signal-transduction networks. Nature Reviews Molecular Cell Biology, Nature, v. 7, n. 11, p. 820-828, novembro, 2006 .
JIMENEZ, C. et al. Stability studies of amphetamine and ephedrine derivatives in urine. Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences, v. 843, n. 1, p. 84 – 93, 2006
JONES, A. W.; HOLMGREN A. Abnormally high concentrations of amphetamine in blood of impaired drivers. Journal of Forensic Sciences, v. 50, n. 5, p. 1215 – 1220, 2005
JOYCE, C. et al. The characterization of selected drugs with amine-containing side chains using electrospray ionization and ion trap mass spectrometry and their determination by HPLC-ESI-MS. Journal of Pharmaceutical and Biomedical Analysis, v. 36, n. 3, p. 465 – 476, 2004
JURADO, C. et al. Rapid analysis of amphetamine , methamphetamine, MDA, and MDMA in urine using solid-phase microextraction, direct on-fiber derivatization, and analysis by GC-MS. Journal of Analytical Toxicology, v. 24, n. 1, p. 11 – 16, 2000
KANKAANPAEAE, A. et al. Single-step procedure for gas chromatography-mass spectrometry screening and quantitative determination of amphetamine-type stimulants and related drugs in blood, serum, oral fluid and urine samples. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, v. 810, n. 1, p. 57 – 68, 2004
KELLY, K. L. The accuracy and reliability of tests for drugs of abuse in urine samples. Pharmacotherapy, v. 8, n. 5, p. 263 – 275, 1988
KIM, T. J.; LEBOURGOIS III, H. W. Banned, but not forgotten: A case of Ephedrine- Induced Psycosis. Journal of Clinical Psychiatry, v. 6, n. 3, p. 136 – 137, 2004
KINDERMANN, W. The problem of doping nd the current doping list. Deutsche Zeitschrift fuer Sportmedizin, v. 55, n. 4, p. 90 – 95, 2004
KOELLIKER, S.; OEHME, M. Structure elucidation of nanogram quantities of unknown designer drugs based on phenylalkylamine derivates by ion trap multiple mass spectrometry. Analytical and Bioanalytical Chemistry, v. 378, n. 5, p. 1294 – 1304, 2004
KRONSTRAND, R. et al. Screening for drugs of abuse in hair with ion spray LC–MS– MS. Forensic Science International, v. 145, p. 183 – 190, 2004
KUNSMAN, G. W. et al. MDA-MDMA concentrations in urine specimens. Journal of Analytical Toxicology, v. 20, n. 7, p. 517 – 521, 1996
KUPIEC, T. et al. Choice of an ELISA assay for screening postmortem blood for amphetamine and/or methamphetamine. Journal of Analytical Toxicology, v. 26, n. 7, p. 513 – 518, 2002
KYLE, P. B. et al. Suspected Pediatric Ingestions: Effectiveness of Immunoassay Screens vs. Gas Chromatography/Mass Spectroscopy in the Detection of Drugs and Chemicals. Journal of Toxicology, Clinical Toxicology, v. 41, n. 7, p. 919 – 925, 2003
LAI, C. Uniform solid-phase extraction procedure for toxicological drug screening in serum and urine by HPLC with photodiode-array detection. Clinical Chemistry, v. 43, n. 2, p. 312 – 325, 1997
LANCAS, F. M. Extração em Fase Sólida (SPE). 1ed. São Carlos. RiMa, 2004. 96p.
LAURE, P.; BINSINGER, C.; LECERF, T. General practitioners and doping in sport: attitudes and experience. British Journal of Sports Medicine, v. 37, .n. 4, p. 335 – 338, 2003
LEUTHOLD, L. A.; VARESIO, E.; HOPFGARTNER, G. Drug tablets instant analysis by desorption-electrospray ionisation mass spectrometry. Spectroscopy Europe, v. 18, n. 2, p. 8 – 12, 2006
LINDEN, R. Análise toxicológica sistemática e farmacogenética em toxicologia forense. In: Simpósio Brasileiro de Cromatografia e Técnicas Relacionadas (SIMCRO 2006), 2, São Pedro, 2006
LIU, S.; WOO, S.; KOH, H. HPLC and GC–MS screening of Chinese proprietary medicine for undeclared therapeutic substances. Journal of Pharmaceutical and Biomedical Analysis, v. 24, p. 983 – 992, 2001
LOOR, R. et al. Multiplex assay of amphetamine, methamphetamine, and ecstasy drug using CEDIA technology. Journal of Analytical Toxicology, v. 26, n. 5, p. 267 – 273, 2002
LOWE, R. H. et al. A validated positive chemical ionization GC/MS method for the identification and quantification of amphetamine, opiates, cocaine, and metabolites in human postmortem brain. Journal of Mass Spectrometry, v. 41, n. 2, p. 175 – 184, 2006
LOWE, R. H. et al. A validated positive chemical ionization GC/MS method for the identification and quantification of amphetamine, opiates, cocaine, and metabolites in human postmortem brain. Journal of Mass Spectrometry, v. 41, n. 2, p. 175 – 184, 2006
LUA, A. C.; LIN, H. R. A Rapid and Sensitive ESI-MS Screening Procedure for Ketamine and Norketamine in Urine Samples. Journal of Analytical Toxicology, v. 28, n. 8, p. 680 – 684, 2004
LUHUA, Z. et al. Chromatographic Separation of (_)-Ephedrine and (_)-Pseudoephedrine in the Traditional Chinese Medicinal Preparation Jiketing Granule. Chemistry and Pharmaceutical. Bulletim, v. 53, n. 11, p. 1494 – 1497, 2005
LURIE, I. S. et al. Use of dynamically coated capillaries for the routine analysis of methamphetamine, amphetamine, MDA, MDMA, MDEA, and cocaine using capillary electrophoresis. Journal of Forensic Sciences, v. 46, n. 5, p. 1025 – 1032, 2001
LURIE, I. S.; HAYS, P. A.; PARKER, K. Capillary electrophoresis analysis of a wide variety of seized drugs using the same capillary with dynamic coatings. Electrophoresis, v. 25, n. 10 – 11, p. 1580 – 1591, 2004
MACHATA, G. Large-scale drug monitoring. (Olympic games 1976). Beitraege zur Gerichtlichen Medizin, v. 35, p. 29 – 36, 1977
MAGGIO, E. T., Enzyme-immunoassay. 1.ed. Boca Raton: CRC, 1988. 295p.
MANDELL, A. J. The Sunday syndrome: a unique pattern of amphetamine abuse indigenous to American professional football. Clinical Toxicology, v. 15, p. 225 – 232, 1979
MARESOVA, V. et al. The Identification of a Chlorinated MDMA. Journal of Analytical Toxicology, v. 29, n. 5, p. 353 – 358, 2005
MARIZ, S. R. Toxicological aspects of fenproporex. Revista Brasileira de Toxicologia, v. 17, n. 1, p. 39 – 47, 2004
MARTINS, L. et al. Simultaneous enantioselective determination of amphetamine and congeners in hair specimens by negative chemical ionization gas chromatography-mass spectrometry. Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, v. 825, n. 1, p. 57 – 62, 2005
agent for the enantioselective quantification of amphetamine -type stimulants in hair. Journal of Chromatography, B: Analytical Technologies in the Biomedical and Life Sciences, Amsterdam, v. 842, n. 2, p. 98 – 105, outubro, 2006
MAUGHAN, R. J. Contamination of dietary supplements and positive drug tests in sport.