What substances or conditions can cause a false positive result for oxycodone?

False Positive Oxycodone Results

The most clinically significant cause of false-positive oxycodone results is oral naltrexone, which metabolizes to noroxymorphone and can trigger positive oxycodone immunoassays. 1

Primary Causes of False-Positive Oxycodone Results

Naltrexone (Most Important)

• Oral naltrexone metabolizes to noroxymorphone, a lesser-known metabolite that directly causes false-positive oxycodone results on standard immunoassay screening 1
• This false-positive can occur repeatedly in patients stabilized on oral naltrexone for alcohol or opioid use disorder 1
• Confirmatory testing with gas chromatography-mass spectrometry (GC-MS) will detect noroxymorphone rather than oxycodone, definitively proving the false-positive 1

Cross-Reactivity from Other Opioids

• Oxymorphone, the metabolite of oxycodone, can be detected by oxycodone immunoassays and may represent metabolism from actual oxycodone use rather than independent oxymorphone use 2
• High-dose morphine (with urine levels in the 15,000-28,000 mg/mL range) has been documented to cause false-positive results on some opioid immunoassays, though this was specifically reported for buprenorphine screens 3

Drug Impurities

• Hydrocodone can be present as an impurity in oxycodone pills at concentrations up to 1%, and hydrocodone or its metabolite hydromorphone may be detected in patients taking only oxycodone 4
• When the ratio of hydrocodone to oxycodone or hydromorphone to oxycodone is <1%, this likely represents an impurity rather than independent drug use 4

Critical Testing Limitations

Immunoassay Screening Tests

• Standard opiate immunoassays poorly detect oxycodone because it is a semisynthetic opioid, which is why specific oxycodone immunoassays were developed 5
• Immunoassay screening tests are presumptive only and susceptible to cross-reactions, requiring confirmation by GC-MS when results are unexpected or will impact clinical decisions 2, 6
• The sensitivity threshold of immunoassays may be too high to detect therapeutic levels of oxycodone, potentially causing false-negative results 7

Detection Variability

• Many laboratories now use specific oxycodone immunoassays that detect both oxycodone and oxymorphone, improving detection compared to traditional opiate screens 2
• The combination of traditional opiate immunoassays with specific oxycodone immunoassays provides 98% sensitivity and specificity for opioid detection 5

Essential Clinical Approach

Before Making Any Clinical Decisions

• Obtain a complete medication history, specifically asking about naltrexone (oral or injectable), all prescribed opioids, over-the-counter medications, and supplements 6, 8
• Discuss unexpected results with the patient in a non-judgmental manner before ordering confirmatory testing, as this can sometimes yield a candid explanation 2
• Contact your laboratory or toxicologist to understand which specific substances are included in their testing panel and the detection thresholds used 2, 6

Confirmatory Testing Requirements

• Request GC-MS confirmatory testing before making any consequential clinical decisions, such as dismissing patients from care, making punitive decisions, or assuming medication diversion 2, 6, 9
• GC-MS can definitively identify specific opioids and metabolites, distinguishing true oxycodone use from false-positives caused by naltrexone metabolites or other cross-reacting substances 2, 1
• If GC-MS detects noroxymorphone rather than oxycodone in a patient taking oral naltrexone, this confirms the false-positive 1

Critical Pitfalls to Avoid

• Never dismiss patients from care or make punitive decisions based solely on immunoassay results without confirmatory testing, as this constitutes patient abandonment and could have severe adverse consequences 2, 9
• Do not assume that a positive oxycodone result always indicates illicit use or diversion—metabolites from prescribed medications (like oxymorphone from oxycodone) can cause positive results 2
• Be aware that false-positive results can have severe consequences in some states, including loss of child custody or legal implications 2, 6
• Understand that drug testing cannot distinguish between appropriate use and misuse of prescribed medications 6