ANNALS OF CLINICAL AND LABORATORY SCIENCE, Vol. 25, No. 4 Copyright © 1995, Institute for Clinical Science, Inc.

Mechanism of Interferences for Gas Chromatography/Mass Spectrometry Analysis of Urine for Drugs of Abuse*f

ALAN H. B. WU, Ph.D.

Toxicology Laboratory, Hartford Hospital, Hartford, CT 06102

ABSTRACT

Although gas chromatography/mass spectrometry (GS/MS) is recognized as the definitive procedure for confirming positive immunoassay screening results of urine for drugs of abuse, targeted GC/MS analysis does have limitations. False negative results can occur when interfering drugs are present at high relative concentrations. If an interfering drug competes with the targeted drug for the derivatization reagent, low results are pro­ duced. If the interfering drug chromatographically co-elutes with the target drug, the ionization efficiency of the target compound by electron impact (El) ionization may be affected. False positive results can also occur through a number of mechanisms. Two substances with the same mass spectrum require gas chromatographic conditions that enable adequate separation of the compounds prior to MS analysis. In the case of optical isomers, special columns or derivatives must be used for identification and quantification. The widespread use of selected ion monitoring may further limit GC/MS assays. Drugs that produce similar high molecular-weight mass fragment ions could potentially interfere if they have similar GC retention times and if inappropriate ions are selected for monitoring. The conversion of one drug to another by the GC/MS instrument itself is a particularly insidious problem. False positive and negative results have serious forensic consequences and must be recognized and avoided. In contrast, the consumption of poppy seeds or meats from livestock given drugs such as methenolone can produce unexpected true positive results for opiates and anabolic steroids, respectively.

Introduction for drugs of abuse, most laboratories use a combination of screening using a non­ Although there are many methods isotopic immunoassay and confirmation available today for the analysis of urine by gas chromatography/mass spectrome­ try. Many consider GC/MS as the “gold * Presented in part at the 1994 Spring Meeting of standard” for confirmation analysis. The the Association of Clinical Scientists, Charleston, SC. Substance Abuse and Mental Health Ser­ t Send reprint requests to: Alan H. B. Wu, Ph.D., Toxicology Laboratory, 80 Seymour Street, P.O. vices Administration (SAMHSA) man­ Box 5037, Hartford, CT 06102-5037. dates the use of targeted GC/MS analysis 319 0091-7370/95/0700-0319 $01.80 © Institute for Clinical Science, Inc. 320 wu for confirming positive results of urine Methodology collected for workplace testing of federal em ployees . 1,2 A “ targeted analysis” is F a l s e N e g a t i v e R e s u l t s directed towards determining the absence or quantitative presence of only Competition for derivatization rea­ a few drugs. This is in contrast to an gents. An important step for most GC/MS “unknown analysis” where the objective assays is derivatization of the target drug. is to identify the presence of as many Derivatization functions to increase the drugs or substances as possible. Most volatility of the substance, improve the laboratories use selected ion monitoring efficiency of chromatographic elution, (SIM) for targeted analysis because this and increase the molecular weight of improves the analytical sensitivity of the mass fragments so that they are more dis­ assay.3 Analysis, by SIM usually involves tinct from low molecular weight “back­ monitoring the intensity of three princi­ ground” mass fragments. Derivatization pal ions of a mass spectrum and comput­ reagents react with specific functional ing ion ratios of responses between ions. groups on the parent molecule including Full-scan mass spectral analysis coupled amides, amines, acids, and hydroxides.4 with a computerized library and search Accurate GC/MS analysis requires routines are necessary for conducting derivatization reactions that are stoichio- unknown analyses. metrically complete, as underivatized Data from GC/MS analysis are consid­ drugs elute at different times and would ered the most defensible in legal pro­ not be detected by analyses targeted ceedings. Some attorneys and lay indi­ towards the derivative. viduals might consider such analyses to As an example of drug interference be beyond challenge. However, GC/MS caused by competition, Brunk described is like any other analytical technique, the GC/MS analysis of the marijuana and there are important limitations. In metabolite 11-nor-A9 -THC-9-carboxylic this paper, mechanisms for false negative acid (9-carboxy THC [tetrahydrocan- and positive results of GC/MS analysis nabinols] ) . 5 As shown in figure 1, this for drugs of abuse are reviewed from assay involves the formation of the published reports. dimethyl derivative with dimethylsulfoxide

c h 3 c « 3 (CH 3 )2 CHCH 2 ^ > -C H C O O H (CH 3 )2 CHCH 2 CHCOOCH 3

COOH

delta-9-THC F ig u r e 1. The presence of ibuprofen can compete with delta-9-THC (tetrahydrocannabinols) for the formation of methyl derivatives. MECHANISM OF INTERFERENCES FOR GC/MS OF URINE FOR DRUGS OF ABUSE 321 (DMSO) and tétraméthylammonium excess to the other, saturation of the ion­ hydroxide (TMAH). The presence of ization source can occur, resulting in a high concentration of ibuprofen inter­ decrease in the ionization efficiency of fered with the derivatization of 9-carboxy both compounds (figure 2B). Under these THC by competing with the derivatiza­ conditions, the concentration of the tar­ tion reagent. This problem can be elimi­ get drug may be dramatically decreased nated by using enough derivatizating by the presence of the interferant. The reagent so that it does not get depleted gas chromatograph normally separates when other potentially interferring drugs drugs from potential interferants so that are present. both are not simultaneously present Interference of the ionization source in the ionization chamber of the mass by coelution. A critical tenant for the spectrometer. However, if pre-analytical success of GC/MS analysis is that the separation does not occur, a substance interaction of a substance with the instru­ that coelutes with the target compound mentation is independent to the pres­ may produce an interference. ence of another substance.6 In figure 2A Specific examples of these interactions is depicted the production of positive have been reported .6 ,7 In one report, the ions and mass fragments from the bom­ detection of cocaine metabolite ben- bardment of electrons for two different zoylecgonine (BE, target compound) was drugs present in equal concentrations. interfered by the coelution of the antifun- The presence of drug A does not interfere gal drug fluconazole (interferant), pres­ with the ability of the electron stream to ent at much higher concentrations rela­ ionize drug B. However, if the concentra­ tive to BE .6 This situation was detected tion of one of the drugs is present in great because a positive immunoassay screen

A. B.

to MS

F igu re 2. A. Two substances (A and B) present in equal and nonsaturating concentrations within the electron impact chamber of a mass spectrometer independently produce parent ions (Al, Bl) and fragments (A2, B2). B. Substance B is present at saturating concentrations relative to the target substance A. Under these conditions, some of the target drug and interferant are unable to be ionized by the electron beam or are unable to reach the filtering segment of the mass spectrometer. 322 wu for BE was unexpectedly negative by Once the presence of a coeluting inter­ GC/MS. In the second example (figure 3), fering compound has been detected, cor­ high concentrations of a methadone rection of false negative results can be metabolite interfered with detection and made by removal of the interférant itself quantitation of BE .7 As shown in figure 3, prior to GC/MS analysis. In the example 2-ethylidene-l,5-dimethyl-3,3-diphenyl- presented in figure 3, EDDP was pyrrolidine (EDDP) coelutes with the removed by thin-layer chromatography cocaine metabolite, resulting in a very resulting in full recovery of BE from the small GC peak at m/z 300, corresponding sam ple.7 Another mechanisms to remove to the major fragment of the pentafluoro- interférants is to alter the gas chromato­ propionic (PFP) derivative of BE. graphic analysis conditions (e.g., chang­ The presence of a coeluting band is ing columns or temperature program) so very obvious when full scan MS analysis that the interférant no longer coelutes is used. In figure 3 is clearly illustrated with the target compound. This may not the presence of a large potentially inter­ always be possible, as interférant peaks fering chromatographic peak. When can be very broad. Moving the interférant selected ion monitoring mass spectro- may affect detection of other important metric techniques are used, however, substances such as drug metabolites. detection of an interférant is not apparent unless one (or more) of the ions selected for the target drug is coincidentally one F a l s e P o s i t i v e R e s u l t s of the major fragments of the interférant. This highlights the importance of using Substances with identical mass spec­ coeluting deuterated internal standards tra. Qualitative identification by mass (IS) . 8 The recovery of a coeluting internal spectrometry is predicated on the standard can be used to evaluate the assumption that no two compounds will quality of the GC/MS analysis, as the produce the identical mass spectrum. presence of a coeluting interférant will Although this may be theoretically true, affect the ionization efficiency of both the in actual practice, many pairs of com­ IS and target drug. Since a constant pounds have mass spectra that are essen­ amount of the IS is added to all samples, tially identical (i.e., within the limits of a low IS recovery might be caused by current instrumentation). For example, a coeluting interférant. the underivatized electron ionization mass spectra of phentermine and meth- amphetamine are indistinguishable from each other because there are only three ions in the spectrum that have an relative abundance that exceeds 10% (m/z 58, 65, and 91).9 The mass spectrum of the meth­ ylated derivative of pentobarbital is also identical to methylated amobarbital under El with major ions at m/z 169 and Time (min) 184.3 In most circumstances, there are F i g u r e 3. The interference of the quantitation significant differences in the gas chro­ of benzoylecgonine (m/z 300) by EDDP (metha­ done metabolite, m/z 277) present in high concen­ matographic retention times to enable trations in urine. (Figure reproduced from O’Con­ differentiation between two compounds nor E, Ostheimer D, Wu AHB. Limitations of that have the same mass spectrum. forensic urine drug testing by methodology and adulteration. AACC Ther Drug Monit-Toxicol For example, the gas chromatogram of a Update 1993;14:275-96, with permission.) mixture of methylated barbiturates MECHANISM OF INTERFERENCES FOR GC/MS OF URINE FOR DRUGS OF ABUSE 323

Retention Time (sec)

FIGURE 4. Gas chromatogram of methylated barbiturates illustrating the differences in retention times between amobarbital and pentobarbital. demonstrating that significant differ­ izing reagent. Although the mass spectra ences in the elution of amobarbital and for these isomers are identical, differ­ pentobarbital is shown in figure 4. ences in retention times enable sepa­ In some cases, however, two function­ rate quantitation. ally different compounds may have the Substances with similar three-ion mass same structure, GC retention times, and spectra. The widespread use of selected mass spectrum. The classic example is d- ion monitoring produces the potential for and 1-methamphetamine. 10 The d-form is false positive results whenever interfer­ an appetite suppressant and central ner­ ing substances are present that have vous system stimulant, and is listed by identical three ion mass spectra, and if the Drug Enforcement Agency (DEA) GC retention times for the interferant are under schedule II. The 1-form is a non­ similar to the target compound. Two sim­ prescription antihistamine (also termed ilar compounds can have the same three- 1-desoxyephedrine) that is available as an ion mass spectra if the major fragmenta­ inhaler (e.g., Vicks Inhaler*). Detection tion patterns occur within areas that are of d-methamphetamine from the 1-form invariant from one molecule to the other. requires use of either a chiral GC col­ For example, the mono-heptafluoro- um n 11 or production of chiral-specific butyric derivatives of ephedrine and derivatives. 12 In figure 5 is illustrated the methamphetamine fragments within the separation of d- and 1-methamphetamine region of the derivatized amide. As using N-trifluoroacetyl-prolyl chloride, a shown in figure 6 , this part of the mole­ commonly used chiral-specific derivativ- cule is the same for both compounds, and ions at m/z 169, 210, and 254 are pro­ duced at essentially the same ion ratios * Proctor and Gamble, Cincinnati, OH 45267. (figure 7) . 13 Under normal circumstances, 324 wu

F ig u r e 5. Gas chro­ matogram and mass spec­ trum of d- and 1-m eth- amphetamine using a chiral-sensitive derivative. (DB-1 GC column, [J&W Scientific, Folsom, CA 95630] and ITS40 GC/ion trap MS [Finnigan Mat, San Jose, CA 95134] with electron impact ionization).

ephedrine and methamphetamine have terone abuse among athletes, with a ratio sufficient differences in retention times exceeding 6:1 indicating external use. In that precise control of GC conditions figure 8 it is shown that the major high would eliminate this problem. However, molecular weight fragments of the PFP it has been found by us that impurities in derivative for both compounds occur at the derivatizing reagent can result in the m/z 401, 417, 565, and 580. To distin­ production of a heptafluorobutyl (HFB)- guish testosterone from epitestosterone, methamphetamine-like substance from it would be more appropriate to select ephedrine, with the same retention time m/z 253 and 270 ions. However, these as methamphetamine . 14 Selection of particular fragments originating from the lower molecular weight ions such as m/z basic steroid backbone structure are 91 and 118, or the use of full mass spec­ present in other natural and synthetic ste­ tral scan analysis would enable differen­ roids. Therefore use of these ions may pro­ tiation between true methamphetamine, duce interferences for other compounds. and artifacts produced by ephedrine. Other investigators have reported simi­ Another example is the PFP-derivative lar difficulties with detection of nortes- of testosterone (T) and epitestosterone tosterone (nandrolone), a widely abused (E), which also have similar GC retention synthetic anabolic steroid listed among times. The T/E ratio is an important those banned by the International Olym­ parameter for testing exogenous testos­ pic Committee. Nandrolone metabolizes

CH 3 254 c h 3 :. 169 H- N C -(C F 2)CF3 F ig u re 6. Mono-HFB derivatives of ephedrine Q and methamphetamine. H OH The derivatization occurs at the site of the secondary amine for both drugs.

HFB-methamphetamfne mono-HFB-ephedrine MECHANISM OF INTERFERENCES FOR GC/MS OF URINE FOR DRUGS OF ABUSE 325

1 0 0 % -i HFB-ephedrine 254

210 © 50%- O c 00 56 69 169 344 F igure 7. Mass spec­ TJ c _l _L trum of the heptafluo- 3 o%- robutyl-methamphet- n amine-like (HFB) < derivatives of ephedrine HFB-methamphetamine 254 and methamphetamine. aj The ion ratios for m/z 169,

to 19-norandrosterone and 19-norepi- port temperatures, the CB-derivative of androsterone. The di-trimethylsilyl ephedrine converts to the CB-metham- (TMS) derivative of 19-norandrosterone phetamine derivative . 14 Other deriva­ has similar GC retention times and three tives such as heptafluorobutyric anhy­ ion mass spectra (m/z 405, 420, and 422) dride and trifluoroacetic anhydride as the di-TMS derivative of a-tocopher- produced similar results. 18 This problem onolactone, a vitamin E metabolite . 16 can be avoided by the use of another Vitamin E is present in many over-the- derivatizing reagent or by decreasing the counter nutritional supplements taken by injection port temperatures. Alternately, athletes such as Met-Rxt or Ultimate samples can be pretreated with periodate Orange,t and false positive results are to oxidize ephedrine and pseudoephed- possible if laboratories use inappropriate rine, converting them to products that do confirmation methods. The use of full not interfere with the GC/MS analysis. 19 scan MS analysis is critical in reducing Rather than requiring more stringent or eliminating the potential of these laboratory techniques, SAMHSA opted to substances for producing false errone­ eliminated this problem by establishing ous results. two criteria for reporting positive meth­ Intra-instrument conversion of one amphetamine confirmations: requiring drug derivative to another. In 1990, a the co-presence of the parent compound SAMHSA-certified laboratory reported at concentrations exceeding 500 ng/mL false positive methamphetamine results and the metabolite (amphetamine) due to the presence of ephedrine on sev­ exceeding 200 ng/mL. While this more eral urine samples. Carbethoxyhexafluo- stringent dual criteria has eliminated the robutyryl (CB) chloride was used as the number of false positive reports, it also derivatizing reagent. 16 Subsequent stud­ has resulted in the production of false ies have shown that at high GC injection negative reports.20

True Positive Results t Met-Rx Substrate Technology, Inc., Newport , Beach, CA 92568. * he result of a urine drug test can be t Next Nutrition, Carlsbad, CA 92008. considered true positive analytically {i.e., 326 wu

100 X 580

a> o TJ c 3 2

. 1 © cc

Mass-to-Charge Ratio (m/z)

i00x 5 8 0

a> 8 -o(0 c 3 -O <

. 1 2s© CC

Mass-to-Charge Ratio (m/z)

FIGU RE 8. Pentafluoropropionic-derivative of testosterone and epitestosterone illustrating the simi­ larity of spectra for masses exceeding m/z 300. (Figure reproduced from Onigbinde TA, Wu AHB, Full-scan gas chromatography-mass spectrometry analysis for drug testing in urine using an ion trap. AACC Ther Drug Monit-Toxicol Update 1992;13(7):9-23, used with permission.) MECHANISM OF INTERFERENCES FOR GC/MS OF URINE FOR DRUGS OF ABUSE 327 the GC/MS-confirmed presence of the Anabolic steroids. Although illegal in target drug) while simultaneously be many countries, anabolic steroids are falsely positive for indicating abuse of used in livestock animals, such as sheep that substance by the tested individual. and cattle, to promote growth and Such findings can be caused by normal w eight.2 5 Eating contaminated meat from dietary ingestion of food. The following treated animals may result in the produc­ discussion gives two specific examples. tion of positive results in urine for ana­ Poppy seeds consumption vs. heroin bolic steroids. In one controlled study, abuse. Individuals who consume foods chickens were injected intramuscularly such as bagels, cakes and rolls containing with methenolone acetate and fed to poppy seeds can produce true positive male volunteers after slaughter. Posi­ results for opiates.21 The concentration of tive results for anabolic steroids were codeine and morphine in poppy seeds obtained in half of the urine samples can vary depending on the quality and collected 24 h after consumption . 2 6 efficiency of seed washing techniques. In In another study, clostebol metabolites one study seed concentrations varied were recovered in urine following from 15 to >300 |xg/g for m orphine and 0 consumption of beef treated with this to 15 (xg/g for codeine .2 2 Urine concentra­ horm one .2 7 These covert true positive tions of subjects given seeds have been results may have significant conse­ as high as 2635 ng/mL for morphine and quences in the highly regulated sports 45 ng/mL for codeine .21 testing arena. The presence of opiates in poppy seeds have complicated the process needed to Conclusion confirm true heroin abuse by opiate test­ ing in urine. Heroin has a half-life in The quality of GC/MS analysis is blood estimated to be 9 minutes2 3 and is dependent on the design of the analysis not detected in urine. It is rapidly hydro­ and attention to safeguard measures. As lyzed first to 6 -monoacetylmorphine nearly all analytical false positive and (6 -MAM) and then to morphine (Figure negative results are due to the presence 9). The detection of 6 -MAM can be used of other drugs and substances in urine, to identify heroin abusers. Unfortunately, improvements in the quality of pre- 6 -MAM also has a short t V2 in blood, esti­ analytical extraction steps are warranted. mated to be about 38 minutes. Neverthe­ Selected ion monitoring is an important less, GC/MS analyses (figure 10) of this technique that have been successfully heroin metabolite have been devel­ used for forensic analysis for many years. oped ,2 4 and are being used for clinical However, results are not as definitive as and forensic purposes. full scan MS analysis, and limitations of

FIGURE 9. The conversion of heroin to 6-monoacetylmorphine and morphine. 328 wu

Mass-to-Charge Ratio (m/z)

F i g u r e 10. Analysis by gas chromatography/mass spectroscopy (GC/MS) of the pentafluoropropioriic- derivative of 6-monoacetylmorphine. (DB-1 GC column [J&W Scientific, Folsom, CA 95630] and ITS40 GC/ion trap MS [Finnigan Mat, San Jose, CA 95134] with electron impact ionization).

SIM must be recognized. Deuterated drug testing programs; final guidelines notice. internal standards should be used to Fed Register 1988;53:11969-89. 2. Department of Health and Human Services. mimic the extraction behavior of targeted Mandatory guidelines for Federal workplace drugs. They can be particularly useful in drug testing programs. Revised mandatory SIM analysis, if the analytical recovery of guidelines. Fed Register 1994;59:29908-31. 3. Onigbinde TA, Wu AHB. Full-scan gas chroma­ the internal standard is routinely calcu­ tography-mass spectrometry analysis for drug lated for unknown samples. An assess­ testing in urine using an ion trap. AACC Ther ment of gas chromatographic peak shapes Drug Monit-Toxicol Update 1992;13:9-23. 4. Knapp DR. Handbook of analytical derivatiza- is also an important quality assurance tion reactions. Wiley, New York, 1979. check. Peak distortions or the presence 5. Brunk SD. False negative GC/MS assay for car- of extended “tailing” can signify a boxy THC due to ibuprofen interference. J Anal Toxicol 1988;12:290-1. degraded column or presence of an inter- 6. Wu AHB, Ostheimer D, Cremese M, Forte E, ferant. These limitations must be recog­ Hill D. Characterization of drug interferences nized if GC/MS is to maintain the title caused by coelution of substances in GC/MS confirmation of targeted drugs in full scan and of “gold standard” for forensic toxi­ SIM modes. Clin Chem 1994;40:216-20. cology analysis. 7. O’Connor E, Ostheimer D, Wu AHB. Limita­ tions of forensic urine drug testing by method­ ology and adulteration. AACC Ther Drug References Monit-Toxicol Update 1993;14:275-96. 8. Joem WA. Marijuana testing in urine: use of a 1. Department of Health and Human Services. hexadeuterated internal standard for extended Mandatory guidelines for Federal workplace linearity, and ion trap vs mass selective gas MECHANISM OF INTERFERENCES FOR GC/MS OF URINE FOR DRUGS OF ABUSE 329

chromatograph/mass spectrometer systems. 18. Hombeck CL, Carrig JE, Czamy RJ. Detection Clin Chem 1992;38:717-9. of a GC/MS artifact peak as methamphetamine. 9. Lehrer M. Application of gas chromatography/ J Anal Toxicol 1993;17:257-63. mass spectrometry instrument techniques to 19. Elsohly MA, Stanford DF, Sherman D, Shah D, forensic urine drug testing. Clin Lab Med 1990; Bemot D, Turner CE. A procedure for elimi­ 10:271-88. nating interferences from ephedrine and 10. Solomon MD, Wright JA. False-positive for related compounds in the GC/MS analysis of ( + )-methamphetamine. Clin Chem 1977;23: amphetamine and methamphetamine. J Anal 1504-7. Toxicol 1992;16:109-11. 11. Cody JT. Determination of methamphetamine 20. Wu AHB, Johnson KG, Wong SS. Impact of enantiomer ratios in urine by gas chromatogra­ revised HHS guidelines for methamphetamine phy/mass spectrometry. J Chromatogr 1992; testing in urine. Clin Chem 1992;38:2352-3. 580:77-95. 21. Fritschi G, Prescott WR. Morphine levels in 12. Fitzgerald RL, Ramos JM, Bogema SC, Poklis urine subsequent to poppy seed consumption. A. Resolution of methamphetamine stereoiso­ Forensic Sei Int 1985;27:111-7. mers in urine drug testing: urinary excretion of 22. Hayes LW, Krasselt WG, Mueggler PA. Con­ R( - ) methamphetamine following use of nasal centration of morphine and codeine in serum inhalers. J Anal Toxicol 1988;12:255-9. and urine after ingestion of poppy seeds. Clin 13. W u AHB, O nigbinde TA, Johnson KG, Wong Chem 1987;33:806-8. SS. Identification of methamphetamines and 23. Baselt RC, Cravey RH. Disposition of Toxic over-the-counter sympathomimetic amines by Drugs and Chemicals in Man. 3rd ed., Year fiill-scan GC/Ion trap MS with electron impact Book Medical Publishers, Inc., Chicago, 1989: and chemical ionizations. J Anal Toxicol 1992; 395-401. 16:137-41. 24. Mule SJ, Casella GA. Rendering the “poppy­ 14. Wu AHB, Wong SS, Johnson KG, Ballatore A, seed defense” defenseless: identification of Seifert WE. The conversion of ephedrine to 6-monoacetylmorphine in urine by gas chroma­ methamphetamine and methamphetamine-like tography/mass spectroscopy. Clin Chem 1988; compounds during and prior to gas chromato­ 34:1427-30. graphic/mass spectrometric analysis of CB and 25. Council directive of 7 March 1988 concerning HFB derivatives. Biol Mass Spectrom 1992;21: the prohibition of use in livestock farming of 278-84. substances having a hormonal action (88/146/ 15. Catlin DH, Kämmerer RC, Hatton CK, Sekera EEC). Offic J Eur Communities 1988;70:16-8. MH, Merdink JL. Analytical chemistry at the 26. Kieman AT, Cowan DA, Myhre L, Nilsson S, Games of the XXIIIrd Olympiad in Los Ange­ Tomten S, Oftebro H. Effect on sports drug les, 1984. Clin Chem 1987;33:319-27. tests of ingesting meat from steroid (methe- 16. Chung BC, Cho HYP, Kim TW, Eom KD, Kwon nolone)-treated livestock. Clin Chem 1994;40: OS, Suh J, Yang J, Park J. Analysis of anabolic 2084-7. steroids using GC/MS with selected ion moni­ 27. Debruycker G, de Sagher R, Van Peteghem toring. J Anal Toxicol 1990;14:91-5. CV. Clostebol-positive urine after consumption 17. Method disputed as NIDA lab incurs false of contaminated meat. Clin Chem 1992;38: positives. Clin Chem News 1990; 16(12): 1-3. 1869-73.