Zinc Sulfate, a Recently Introduced Urinary Adulterant Can Invalidate Urine Cotinine Test Using Immunoassay but Has Less Effect on Liquid Chromatography Combined With Tandem Mass Spectrometry-Based Test

Ther Drug Monit. 2015 Oct;37(5):681-4. doi: 10.1097/FTD.0000000000000186.


Objective: Zinc sulfate is a recently introduced urinary adulterant, which causes false-negative results with immunoassays used for screening drugs of abuse in urine but whether zinc sulfate also could invalidate urine cotinine assay using immunoassay or liquid chromatography combined with mass spectrometry has never been studied.

Design and method: Four urine pools containing none detected to high levels of cotinine were analyzed using DRI cotinine immunoassay on the Olympus 640 analyzer as well as using liquid chromatography combined with tandem mass spectrometry. Specimens were reanalyzed after supplementing with various amounts of zinc sulfate that are known to invalidate immunoassays used for drugs of abuse testing.

Results: Zinc sulfate in all concentrations studied caused false-negative results using immunoassays, but zinc sulfate also reduced cotinine values by approximately 2.1%-38.4% when analyzed using liquid chromatography combined with mass spectrometry.

Conclusions: Zinc sulfate caused false-negative cotinine result when DRI immunoassay was used and also had small to moderate impact on liquid chromatography combined with tandem mass spectrometry-based assay for urine cotinine.

MeSH terms

  • Chromatography, Liquid / methods*
  • Cotinine / urine*
  • False Negative Reactions
  • Humans
  • Immunoassay
  • Tandem Mass Spectrometry / methods*
  • Zinc Sulfate / urine*


  • Zinc Sulfate
  • Cotinine