What substances cross-react with barbiturates (barbituric acid derivatives) on drug tests?

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From the Guidelines

Barbiturates that can test positive on drug screens include phenobarbital, secobarbital, pentobarbital, butalbital, and amobarbital. These medications are typically prescribed for seizure disorders, as sedatives, or for anesthesia. Some medications that aren't barbiturates can also cause false positive results, including certain NSAIDs (like ibuprofen), some antibiotics, and muscle relaxants 1. Standard urine drug tests typically detect barbiturates for 2-4 days after use, though chronic users may test positive for up to 6 weeks since these drugs accumulate in fatty tissues. Blood tests generally detect barbiturates for 1-2 days, while hair tests can identify use for up to 90 days. It's essential to note that drug testing can yield false-positive or false-negative results due to cross-reactivity with unrelated substances in the urine 1. Therefore, it's crucial to inform testing facilities about any prescription medications you're taking to avoid misinterpretation of results. Barbiturates work by enhancing the effect of GABA, an inhibitory neurotransmitter in the brain, which explains their sedative properties and why they appear on drug panels designed to detect substances that affect the central nervous system. Key points to consider when testing for barbiturates include:

  • The type of drug test used (urine, blood, or hair)
  • The timing of the test in relation to the last use of the drug
  • The potential for false-positive results due to cross-reactivity with other substances
  • The importance of informing testing facilities about any prescription medications being taken 1.

From the Research

Drugs that Test Positive for Barbiturates

The following drugs may test positive for barbiturates:

  • Brompheniramine 2
  • Bupropion 2
  • Chlorpromazine 2
  • Clomipramine 2
  • Dextromethorphan 2
  • Diphenhydramine 2
  • Doxylamine 2
  • Ibuprofen 2
  • Naproxen 2
  • Promethazine 2
  • Quetiapine 2
  • Quinolones (ofloxacin and gatifloxacin) 2
  • Ranitidine 2
  • Sertraline 2
  • Thioridazine 2
  • Trazodone 2
  • Venlafaxine 2
  • Verapamil 2

Barbiturates and their Combination Drugs

Barbiturates and their combination drugs that can be detected using gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) include:

  • Acecarbromal 3
  • Allobarbital 3
  • Amobarbital 3
  • Aprobarbital 3
  • Barbital 3
  • Brallobarbital 3
  • Bromisoval 3
  • Butabarbital 3
  • Butalbital 3
  • Butobarbital 3
  • Carbromal 3
  • Clomethiazole 3
  • Crotylbarbital 3
  • Cyclobarbital 3
  • Cyclopentobarbital 3
  • Diethylallylacetamide 3
  • Dipropylbarbital 3
  • Glutethimide 3
  • Guaifenesin 3
  • Ethinamate 3
  • Heptabarbital 3
  • Hexobarbital 3
  • Meprobamate 3
  • Methaqualone 3
  • Metharbital 3
  • Methohexital 3
  • Methylphenobarbital 3
  • Methyprylone 3
  • Pentobarbital 3
  • Phenobarbital 3
  • Propallylonal 3
  • Pyrithyldione 3
  • Secobarbital 3
  • Thiobutabarbital 3
  • Thiopental 3
  • Vinbarbital 3
  • Vinylbital 3

False-Positive Urine Drug Screens

False-positive urine drug screens for barbiturates can occur with certain medications, including:

  • Antihistamines 2
  • Antidepressants 2
  • Antibiotics 2
  • Analgesics 2
  • Antipsychotics 2
  • Nonprescription agents 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Commonly prescribed medications and potential false-positive urine drug screens.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2010

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Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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