True Positives in Opioid Immunoassay Testing
True positives in opioid immunoassay testing occur when the test correctly identifies the presence of opioids that are actually in the patient's system, though these tests have significant limitations in sensitivity and specificity for different opioid compounds. 1
Understanding Opioid Immunoassay Testing
Opioid immunoassays are qualitative screening tests that detect specific drug classes rather than individual medications. These tests have several important characteristics:
- They are primarily designed to detect morphine and codeine with high sensitivity 2
- They have variable and often decreased sensitivity for synthetic and semi-synthetic opioids like oxycodone, hydrocodone, and hydromorphone 3, 4
- They provide qualitative results (positive/negative) based on predetermined cutoff values 1
Detection Windows
True positives will only occur when testing within the appropriate detection window:
- Most opioids: 1-3 days after use 1
- Synthetic opioids: 1-2 days 1
- Fentanyl: less than 30 hours after last use 1
Factors Affecting True Positive Results
Opioid-Specific Sensitivity
Different opioids have varying detection rates with standard immunoassays:
- Morphine and codeine: High sensitivity (primary targets) 2
- Oxycodone and hydrocodone: Reduced sensitivity, often requiring specific immunoassays 3
- Hydromorphone: One study found 72.3% of specimens from patients prescribed hydrocodone or hydromorphone that screened negative actually contained these drugs when tested by GC/MS 4
- Fentanyl: Standard opiate immunoassays often miss fentanyl, requiring specific fentanyl immunoassays 5
Concentration Thresholds
True positives depend on the established cutoff concentration:
- Standard cutoff for opiate immunoassays: 300 ng/mL (morphine equivalents) 2
- Lower cutoffs (e.g., 25 ng/mL) may detect opiates for shorter periods but with higher sensitivity 2
- Oxycodone-specific immunoassays typically use a cutoff of 300 ng/mL 3
Limitations of Immunoassay Testing
Even when true positives occur, several limitations exist:
- Cross-reactivity varies between different immunoassay products 1, 6
- Some immunoassays show plateauing responses at higher concentrations 2
- Detection times vary by specific opioid (15-54 hours depending on the drug and assay) 2
- Immunoassays cannot distinguish between different opioids within the same class 7
Confirmatory Testing
Due to limitations of immunoassays, confirmatory testing is essential to verify true positives:
- Gas chromatography/mass spectrometry (GC-MS) or liquid chromatography/mass spectrometry (LC-MS/MS) are the gold standards for confirmation 1
- Confirmatory testing should be used when:
- There's a need to detect specific opioids not well-identified on standard immunoassays
- Results are unexpected or inconsistent with clinical expectations
- Specific opioid identification is needed 1
Clinical Implications
When interpreting true positives:
- A positive opiate test may not detect all prescribed opioids, potentially leading to false accusations of non-adherence 7, 4
- The absence of expected opioids should prompt consideration of:
- Timing of last dose relative to testing
- Metabolic variations
- Technical limitations of the assay 1
- Positive results should never be used alone to discharge patients from practice, as this violates the principle of non-abandonment 7
Best Practices
To optimize detection of true positives:
- Use opioid-specific immunoassays when monitoring for specific drugs like oxycodone 3
- Consider lower thresholds when adherence monitoring is the primary goal 4
- Establish a working relationship with laboratory toxicologists who can assist with interpretation 7
- Use confirmatory testing when results will change treatment approach or patient education 5
True positives in opioid immunoassay testing represent actual detection of opioids in the system, but clinicians must understand the significant limitations of these tests to avoid misinterpretation and inappropriate clinical decisions.