False-negative results in the immunoassay analysis of drugs of abuse: can adulterants be detected by sample check test?

Ann Clin Biochem. 2018 May;55(3):348-354. doi: 10.1177/0004563217725089. Epub 2017 Sep 20.


Background The dilution or adulteration of urine is a serious problem in drugs of abuse testing. Tests to identify adulteration are currently available. This study investigated the ability of the CEDIA® sample check to detect adulteration. Methods Eight different drugs of abuse were added to a urine sample obtained from a healthy, drug-free subject: 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), 3,4-methylenedioxyamphetamine, benzoylecgonine, D-amphetamine sulphate, ethyl-D-glucuronide, morphine sulphate, oxazepam, (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol. Urine samples were diluted to yield three samples of drugs of abuse concentrations close to general cut-offs as used in methadone treatment centres, by health authorities for psychological tests and in traffic medicine. Aspirin, citric acid, CrO3, H2O2, soap, sodium metaborate, vitamin C were added in three, HCl and NaOH in one, and NaN3 in two concentrations. All samples were measured with commercially available immunological assays shortly after sample preparation and 24 h later. All samples were further analysed with the CEDIA® sample check reaction which may identify adulteration. Results Oxidizing reagents (H2O2 or CrO3) are most effective in interfering in the measurement of benzoylecgonine, EDDP, ethyl-D-glucuronide and morphine sulphate. The measurement of (-)-11-nor-9-carboxy-Δ9-tetrahydrocannabinol is affected by many adulterants. Adulteration with HCl and NaOH was identified with the sample check reaction. NaN3 generated false negative results for a number of drugs of abuse. Conclusions Urine samples with drugs of abuse concentrations above cut-offs can be successfully tampered with adulterants in a way which cannot be detected with the CEDIA® sample check assay.

Keywords: CEDIA® sample check; Drugs of abuse; adulteration; immunoassays.

MeSH terms

  • Drug Contamination*
  • False Negative Reactions
  • Humans
  • Illicit Drugs / urine*
  • Immunoassay / methods*
  • Immunoassay / standards
  • Substance Abuse Detection / methods*


  • Illicit Drugs