The trazodone metabolite meta-chlorophenylpiperazine can cause false-positive urine amphetamine immunoassay results

J Anal Toxicol. 2011 Jul;35(6):364-8. doi: 10.1093/anatox/35.6.364.


Amphetamines and methamphetamines are part of an important class of drugs included in most urine drugs of abuse screening panels, and a common assay to detect these drugs is the Amphetamines II immunoassay (Roche Diagnostics). To demonstrate that meta-chlorophenylpiperazine (m-CPP), a trazodone metabolite, cross-reacts in the Amphetamines II assay, we tested reference standards of m-CPP at various concentrations (200 to 20,000 g/L). We also tested real patient urine samples containing m-CPP (detected and quantified by HPLC) with no detectable amphetamine, methamphetamine, or MDMA (demonstrated by GC MS). In both the m-CPP standards and the patient urine samples, we found a strong association between m-CPP concentration and Amphetamines II immunoreactivity (r = 0.990 for the urine samples). Further, we found that patients taking trazodone can produce urine with sufficient m-CPP to result in false-positive Amphetamines II results. At our institution, false-positive amphetamine results occur not infrequently in patients taking trazodone with at least 8 trazodone-associated false-positive results during a single 26-day period. Laboratories should remain cognizant of this interference when interpreting results of this assay.

MeSH terms

  • Amphetamine / blood
  • Amphetamine / urine*
  • Anti-Anxiety Agents / blood
  • Anti-Anxiety Agents / urine*
  • False Positive Reactions
  • Humans
  • Immunoassay
  • Piperazines / standards
  • Piperazines / urine*
  • Substance Abuse Detection*
  • Substance-Related Disorders / blood
  • Substance-Related Disorders / urine
  • Trazodone / blood
  • Trazodone / urine*


  • Anti-Anxiety Agents
  • Piperazines
  • Amphetamine
  • 1-(3-chlorophenyl)piperazine
  • Trazodone