Ask the Expert: False Positive Amphetamine Urine ScreensPublished on Practical Pain Management (http://www.practicalpainmanagement.com)

Ask the Expert: False Positive Amphetamine UrineScreens

January/February 2015By McKenzie C Ferguson, PharmD, BCPS [1] and Emil Borowiak, PharmD Candidate [2] Volume 15, Issue #1

Question: What can cause a false positive urine drug screening for amphetamine?

[3]

Urine drug screenings are useful diagnostic tests. In chronic pain management, drug testing can assessthe appropriate intake of drugs, help with the diagnosis of substance abuse, and improve drugmanagement.1 Screening for illicit drugs, including amphetamine, can be useful in assessing andmonitoring patients with chronic pain. It is important to consider the potential for false positive resultswhen the results of urine drug screenings for amphetamines are interpreted.

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Ask the Expert: False Positive Amphetamine Urine ScreensPublished on Practical Pain Management (http://www.practicalpainmanagement.com)

[4]

Urine screenings for amphetamines commonly involve the use of immunoassays. Multipleimmunoassays are available, and they all share similar basic methodology. In these tests, a sample ofurine or bodily fluid is added to a solution containing antibodies or immunoglobulins, which bind totargeted analytes. By interacting with specific structures, the immunoglobulins signal the presence ofcertain drugs.2 Immunoassays frequently are used in initial urine drug screenings because they providerapid results, cost relatively little, and are commercially available. However, false positives are possibleand must be considered when interpreting results.

Immunoassays often lack the specificity to target individual drugs and typically screen for structurallyrelated compounds. Immunoassays for amphetamines can detect several related chemicals, includingmethamphetamine, 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine(MDMA), and methylenedioxyethylamphetamine (MDEA), that share a common structure that includes aphenyl ring and an amino group connected by a two-carbon side chain.3 However, these structuralelements also can be found in other non-amphetamine drugs as shown in Figure 1 (below), and this mayresult in false positive urine screenings.4-7

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Ask the Expert: False Positive Amphetamine Urine ScreensPublished on Practical Pain Management (http://www.practicalpainmanagement.com)

[5]

For example, the commonly used decongestants pseudoephedrine and phenylephrine share similarstructural characteristics with amphetamines, and cross-reactivity with screenings has beendocumented.2,8 A case report linked the use of intravenous (IV) phenylephrine to a false positiveamphetamine screening.9 Upon admission, the patients routine immunoassay for amphetaminesshowed a negative result, but after 3 days, a repeat analysis was positive for amphetamine. Aconfirmatory test was ordered and identified IV phenylephrine as a likely cause of the false positive.

Another drug that has been associated with false positive results for amphetamine is 1,3dimethylamylamine (DMAA). DMAA has sympathomimetic activity and is an ingredient in some dietaryand weight-loss supplements. A case report linked a false positive amphetamine screening to use of theweight-loss supplement Oxyelite Pro.10 In addition, a review of drug screenings conducted by theDepartment of Defense showed that DMAA was associated in 124 cases out of 134 false-positiveamphetamine samples. Positive amphetamine screens from 2 initial separate immunoassays weredetermined to be false positive in confirmatory testing.11 Identifying pseudoephedrine, phenylephrine,and DMAA as possible causes of false positives is especially problematic because they are available over-the-counter, causing some patients to be unaware of their intake.

In addition to weight-loss supplements, bupropion, which is used as an antidepressant and smokingcessation aid, also is structurally similar to amphetamine and has been associated with false positivescreenings. A retrospective chart review of 10,011 urine drug screens found that of 362 initial positiveamphetamine tests, 128 (35%) were false positives. In 53 of these false positives (41%), use ofbupropion was documented.12 A case report also described a patient taking 300 mg of bupropion dailyand testing falsely positive for amphetamines. A reference test, which added bupropion to drug-freeurine, showed that the cross-reactivity of bupropion with the amphetamine immunoassay ranged from3% to 17%, depending on concentration.13

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Ask the Expert: False Positive Amphetamine Urine ScreensPublished on Practical Pain Management (http://www.practicalpainmanagement.com)

Other drugs can undergo metabolism and cause false positive results. Meta-chlorophenylpiperazine, ametabolite of trazodone, has shown in vitro activity with a Roche amphetamine urine immunoassay.Testing of 6 patients taking trazodone showed that 3 tested falsely positive for amphetamines.14

Labetalol, promethazine, chlorpromazine, and metformin also have been associated with false positiveamphetamine screenings.15-17 Fenofibrate was identified as the cause of a false positive urineamphetamine screening in a patient after 2 separate immunoassays were positive.17 In that case,fenofibrate was discontinued, after which repeat urine screenings were negative.

Follow-up Testing

Positive amphetamine immunoassay screening test results can be confirmed with gas chromatography-mass spectrometry tests (GC-MS). GC-MS separates samples into fragments that are specific to eachindividual compound. Because each fragment pattern can be linked to a single molecular compound, GC-MS is much more specific than immunoassays and can detect the presence and amount of each drugscreened.18

While urine drug screenings are valuable tools in pain management, they have limitations, including thepotential for false positives. For amphetamines, most incidents of false positives can be related to adrugs structure, but case reports and retrospective reviews have associated many drugs with falsepositives. Following a positive drug screening, the possibility of a false positive always should beconsidered. A thorough review of the patients vital signs?, relevant history, and recent medicationsshould be conducted, with additional analysis with more specific tests such as GC-MS, if warranted.

References: References

1. Trescot AM, Boswell MV, Atluri SL, et al. Opioid guidelines in the management of chronic non-cancer pain. Pain Physician. 2006;9(1):1-39.

2. Lee M. Interpreting Laboratory Data. 4th ed. Bethesda MD: American Society of Health-SystemPharmacists, 2009.

3. Beal JM, Block JH. Wilson and Gisvolds Textbook of Organic Medicinal and PharmaceuticalChemistry. 12th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2011.

4. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 3007. Amphetamine.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007&loc=ec_rcs. AccessedDecember 16,,2014.

5. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 7753. 1,3-Dimethylpentylamine.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=7753&loc=ec_rcs. AccessedDecember 16, 2014.

6. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 7028. Pseudoephedrine.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=7028&loc=ec_rcs. AccessedDecember 16, 2014.

7. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 444. bupropion.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=444&loc=ec_rcs. AccessedDecember 16, 2014.

8. DePriest AZ, Knight JL, Doering PL, Black DL. Pseudoephedrine and false-positive immunoassayurine drug tests for amphetamine. Pharmacotherapy. 2013;33(5):e88-e89.

9. Curtin LB, Cawley MJ. Immunoassay cross-reactivity of phenylephrine and methamphetamine. Pharmacotherapy. 2012;32(5):e98-e102.

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Ask the Expert: False Positive Amphetamine Urine ScreensPublished on Practical Pain Management (http://www.practicalpainmanagement.com)

10. Pavletic AJ, Pao M. Popular dietary supplement causes false-positive drug screen foramphetamines. Psychosomatics. 2014;55(2):206-207.

11. Vorce SP, Holler JM, Cawrse BM, Magluilo J Jr. Dimethylamylamine: a drug causing positiveimmunoassay results for amphetamines. J Anal Toxicol. 2011;35(3):183-187.

12. Casey ER, Scott MG, Tang S, Mullins ME. Frequency of false positive amphetamine screens dueto bupropion using the Syva EMIT II immunoassay. J Med Toxicol. 2011;7(2):105-108.

13. Vidal C, Skripuletz T. Bupropion interference with immunoassays for amphetamines and LSD. Ther Drug Monit. 2007;29(3):373-375.

14. Baron JM, Griggs DA, Nixon AL, Long WH, Flood JG. The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results. J AnalToxicol. 2011;35(6):364-368.

15. Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA. Commonly prescribed medications andpotential false-positive urine drug screens. Am J Health Syst Pharm. 2010;67(16):1344-1350.

16. Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screenimmunoassays: a review. J Anal Toxicol. 2014;38(7):387-396.

17. Kaplan YC, Erol A, Karada B. False-positive amphetamine/ecstasy(MDMA/3,4-methylenedioxymethamphetamine) (CEDIA) and ecstasy(MDMA/3,4-methylenedioxymethamphetamine) (DRI) test results with fenofibrate. Ther DrugMonit. 2012;34(5):493-495.

18. Markway EC, Baker SN. A review of the methods, interpretation, and limitations of the urine drugscreen. Orthopedics. 2011;34(11):877-881.

View Sources [6] References

1. Trescot AM, Boswell MV, Atluri SL, et al. Opioid guidelines in the management of chronic non-cancer pain. Pain Physician. 2006;9(1):1-39.

2. Lee M. Interpreting Laboratory Data. 4th ed. Bethesda MD: American Society of Health-SystemPharmacists, 2009.

3. Beal JM, Block JH. Wilson and Gisvolds Textbook of Organic Medicinal and PharmaceuticalChemistry. 12th ed. Baltimore, MD: Lippincott Williams & Wilkins, 2011.

4. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 3007. Amphetamine.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=3007&loc=ec_rcs. AccessedDecember 16,,2014.

5. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 7753. 1,3-Dimethylpentylamine.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=7753&loc=ec_rcs. AccessedDecember 16, 2014.

6. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 7028. Pseudoephedrine.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=7028&loc=ec_rcs. AccessedDecember 16, 2014.

7. National Center for Biotechnology Information. Open Chemistry Database. Compound Summaryfor CID 444. bupropion.http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=444&loc=ec_rcs. AccessedDecember 16, 2014.

8. DePriest AZ, Knight JL, Doering PL, Black DL. Pseudoephedrine and false-positive immunoassayurine drug tests for amphetamine. Pharmacotherapy. 2013;33(5):e88-e89.

9. Curtin LB, Cawley MJ. Immunoassay cross-reactivity of phenylephrine and methamphetamine. Pharmacotherapy. 2012;32(5):e98-e102.

10. Pavletic AJ, Pao M. Popular dietary supplement causes false-positive drug screen foramphetamines. Psychosomatics. 2014;55(2):206-207.

Page 5 of 6

Ask the Expert: False Positive Amphetamine Urine ScreensPublished on Practical Pain Management (http://www.practicalpainmanagement.com)

11. Vorce SP, Holler JM, Cawrse BM, Magluilo J Jr. Dimethylamylamine: a drug causing positiveimmunoassay results for amphetamines. J Anal Toxicol. 2011;35(3):183-187.

12. Casey ER, Scott MG, Tang S, Mullins ME. Frequency of false positive amphetamine screens dueto bupropion using the Syva EMIT II immunoassay. J Med Toxicol. 2011;7(2):105-108.

13. Vidal C, Skripuletz T. Bupropion interference with immunoassays for amphetamines and LSD. Ther Drug Monit. 2007;29(3):373-375.

14. Baron JM, Griggs DA, Nixon AL, Long WH, Flood JG. The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results. J AnalToxicol. 2011;35(6):364-368.

15. Brahm NC, Yeager LL, Fox MD, Farmer KC, Palmer TA. Commonly prescribed medications andpotential false-positive urine drug screens. Am J Health Syst Pharm. 2010;67(16):1344-1350.

16. Saitman A, Park HD, Fitzgerald RL. False-positive interferences of common urine drug screenimmunoassays: a review. J Anal Toxicol. 2014;38(7):387-396.

17. Kaplan YC, Erol A, Karada B. False-positive amphetamine/ecstasy(MDMA/3,4-methylenedioxymethamphetamine) (CEDIA) and ecstasy(MDMA/3,4-methylenedioxymethamphetamine) (DRI) test results with fenofibrate. Ther DrugMonit. 2012;34(5):493-495.

18. Markway EC, Baker SN. A review of the methods, interpretation, and limitations of the urine drugscreen. Orthopedics. 2011;34(11):877-881.

First published on: January 31, 2015 Source URL: http://www.practicalpainmanagement.com/resources/diagnostic-tests/ask-expert-false-positive-amphetamine-urine-screens

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