Wednesday, February 19, 2014

A littly ditty about immunoassays...


I had a urine drug test and my doctor/probation officer/random person told me I was positive for amphetamines. Why did I test positive? I've never taken amphetamines in my life.


More than likely, you have have consumed an amphetamine drug at least once in your life. There are more drugs in the amphetamine/phenethylamine family than just amphetamine (Adderall) and illicit methamphetamine, typically known as "crystal meth". One very common drug in this class is pseudoephedrine, typically used as a nasal decongestant in medications such as Allegra-D, Mucinex-D, Sudafed, and Zyrtec-D.

But the first question that I would ask is, was the test an immunoassay screen? Immunoassay screening tests are based on the principle that antibodies are able to recognize and bind to the drug of interest. These antibodies are designed to be highly selective – meaning they preferentially bind to the drug of interest. In the absence of the drug of interest, this preferential binding does not eliminate the possibility of binding to other drugs that have similar chemical characteristics. This secondary binding is commonly referred to as a “false positive” result. Unfortunately, it is not possible to design an antibody that binds to a single drug exclusively. Additionally, given the myriad of drugs and drug metabolites, it is also not possible to evaluate all possible “false-positives.”

Historically, an amphetamines immunoassay  uses either amphetamine or methamphetamine as a target compound, but it is very susceptible to other cross-reacting substances leading to “false positive” screening results. The following drugs have been known to cross react with various amphetamine immunoassay tests:

Amantadine, Bupropion, Chloroquine, Chlorpromazine, Desipramine, Ephedrine, Fenfluramine, Labetalol, Mexiletine, Procainamide, Phentermine, Phenylephrine, Pseudoephedrine, Ranitidine, Trazodone (mCPP is formed as a metabolite)

 So, it is important to keep a detailed list of substances consumed over the past 7-10 days. Simple use of over-the-counter Zantac (ranitidine) for heartburn or GERD could lead to a positive immunoassay test for amphetamines. Or use of a nasal decongestant such as pseudoephedrine could lead to a positive immunoassay test for amphetamines. The use of prescription medication Adipex (phentermine) could easily cause a positive immunoassay test for amphetamines.
The second question I would ask is, was a confirmatory test completed? While the screening test can be valuable for interpretation of urine toxicology results, especially in an emergency medicine situation, the possibility of “false positive” results is the primary reason for submitting the specimen to a laboratory for confirmatory testing. The laboratory confirmation testing utilizes either gas chromatography (GC) or liquid chromatography (LC) coupled to mass spectrometry (MS). A properly validated confirmatory test is not susceptible to the “false positive” results associated with immunoassay screening techniques. The mass spectrometric analysis provides what is effectively a “chemical fingerprint” pattern that is unique for each drug.  IF a confirmatory test was not completed, request it! While the scope of an assay is highly dependent on the individual laboratory doing the analysis, from my experience, the routine confirmatory urine amphetamines test only monitors amphetamine, MDA, MDMA, and methamphetamine. Some labs offer an expanded amphetamines panel and may include compounds such as ephedrine, MDEA, and pseudoephedrine or even other substituted cathinones such as MDPV and methylone.

If one tests positive for amphetamine and/or methamphetamine by a mass spectrometry- based method, then one has been exposed to or consumed a drug that either contains amphetamine and/or methamphetamine or metabolizes to either drug. It is also important to note that a drug that contains amphetamine only or metabolizes to amphetamine only will not result in a mass spectrometry positive result for methamphetamine. The only way to have methamphetamine in the urine is to consume a drug containing methamphetamine or one that metabolizes to methamphetamine. Methamphetamine will then metabolize to amphetamine. The following list is comprised of drugs that would be considered as true positives for amphetamine and methamphetamine.

Drugs that contain amphetamine:
  • Adderall
  • Benzedrine
  • Biphetamine
  • Dexedrine
  • Durophet
  • Procentra
  • Zenzedi
Drugs that contain methamphetamine:
  • Desoxyn (d-methamphetamine)
  • Vick's inhaler (l-methamphetamine)
  • Illicit methamphetamine
Drugs that metabolize to amphetamine:
  • Clobenzorex
  • Ethylamphetamine
  • Captagon (Fenethylline)
  • Tegisec (Fenproporex)
  • Pondinil (Mefenorex)
  • Prenylamine
  • Vyvanse
Drugs that metabolize to methamphetamine and amphetamine:
  • Didrex (Benzphetamine)
  • Dimethylamphetamine
  • Femprofazone
  • Fencamine
  • Furfenorex
  • Deprenyl (Selegiline)

I hope this helps in understanding false positives from a screening test (specifically an amphetamines urine immunoassay test) and the importance of a confirmatory test. I receive the question on a regular basis, so I thought I would address it here. And as I always say, when it doubt, confirm.




  1. Can Loratadine make you test positive for methamphetamine

    1. No, loratidine will not cause a positive result for amphetamine or methamphetamine on a confirmatory test (mass spectrometry based).

  2. Can bupropion hcl test positive for d-methamphetamine to the extent that the isotomers can only be differentiated using a chiral column?

    1. Bupropion would not cause a positive result for amphetamine or methamphetamine on a confirmatory test (mass spectrometry based).

  3. Will rantadine test as a positive for amphetamines/meth amphetamines in a secondary drug test

    1. No, ranitidine will not cause a positive result for amphetamine or methamphetamine on a confirmatory test (mass spectrometry based).

  4. What about Allegra D? GC/MS days methamphetamine

  5. Can Benzedrex nasal decongestant cause a false positive? If so, does it matter what type of confirmation/secondary test is run to validate?

  6. Can clartin d cause a false positive for meth in a lab test

  7. Can clartin d cause a false positive for meth in a lab test

  8. Can clartin d cause a false positive for meth in a lab test

  9. Can clartin d cause a false positive for meth in a lab test

  10. A yr or so ago I was in a pain mgmt and got a false polite for fentanyl which I did not have n can not take.I asked for retest and they refused. I offered to pay for my own n still they refused even though I was going through custody battle w my sons father and that false positive cld of seriously hurt me in court they still refused. Due to this I left n quit docs n meds but am now finding I need antidepressant again and they want to drug test me in order for me to get them.Another false positive cld cause me to lose visits w my Lil boy besides why must I drug test to get effexor for depression n what can I do if this happens again? I can not afford a lawyer and cld not find anybody that wld retest or explain why that was in my system.I no longer trust these tests or the ppl giving them I'm scared I'll lose seeing my son all together if this were to happen again.I honestly don't know what to do they've got me between a rock n a hard place bcuz I need my antidepressant and can't get it without risking the only thing that matters to me.. my son.

  11. Failed a UA yesterday for METH! I have never touched meth! I took a Zantac the night prior... I had them send it to the lab! My question is what the hell!?

  12. if the screen test was positive for amphetamines and I was taking Wellbutrin
    would the GC/MS be positive for amphetamine level of 396 ng/ml?

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