Urine drug testing (UDT) is considered one of the mainstays of adherence monitoring in conjunction with prescription monitoring programs and other screening tools; however, UDT is associated with multiple limitations secondary to potential pitfalls related to drug metabolism, reliability of the tests, and the knowledge of the pain physician.¹ The practice of UDT is more common in a noncancer pain setting than in an oncology or primary care setting; however, it may be utilized in a punitive manner in efforts to “catch” the patient with an inappropriate positive or negative screen result. Unfortunately, this often results in dismissal of the patient from the practice. Drug testing is most commonly used for two reasons: to identify substances that should not be present in the urine (forensic testing) and to detect the presence of prescribed medications (compliance testing).

The use of UDT to monitor patients on chronic opioid therapy (COT) treated in a pain clinic is reasonable; however, this testing is not mandatory for all patients on COT in all settings. The use of UDT should be based on the clinical judgment of the prescribing clinician; however, some clinicians and/or clinics test all patients on COT sporadically based on policy. Katz and Fanciullo² propose that although further research is needed, it may be easier and more uniform to conduct routine urine toxicology testing in all patients with chronic pain treated with opioids. By adopting a uniform policy of testing, stigma is reduced while ensuring that those persons dually diagnosed with pain and substance use disorders receive optimal care. With careful explanation of the purpose of testing, patient concerns can be easily addressed.^3,4

Abnormal UDT results of patients on COT in a chronic pain clinic generally include absence of the prescribed opioid, presence of nonprescribed drugs, presence of illegal drugs, and adulterated urine specimens.⁵

Fishbain and colleagues gathered urine toxicology results among 122 patients who were prescribed opioids for noncancer pain and found abnormal results in 43% of this sample.⁶ Michna and colleagues published a report on 226 patients primarily with chronic back pain and found 46.5% of the sample to have abnormal urine toxicology.⁵ In a retrospective study of 470 patients, 4 of 10 patients prescribed opioids also had abnormal urine toxicology.² In 2003, Katz and colleagues reported that approximately 20% of patients with persistent pain on COT who seem compliant will test positive for an illicit drug and/or another non-prescribed opioid.⁷ Cone et al. analyzed a large number (n = 10,922) of urine samples from patients with persistent pain on COT and found that the overall prevalence of illicit drug use was 10.9%.⁸ The illicit drugs found in the urine of these patients most often were marijuana, cocaine, and ecstasy-related drugs.⁸ Couto and colleagues reported that over 30% of UDT results in chronic pain patients contained at least one other controlled substance in addition to the prescribed opioid.⁹ These studies underscore the importance of urine toxicology testing along with behavioral observation and self-report measures to help identify aberrant drug-related behaviour.¹⁰

The health care professional (HCP) must know which drugs to test for and by what methods, as well as the expected use of the results. Manchikanti and colleagues¹¹ studied the diagnostic accuracy of POC testing with immunoassay compared to laboratory testing with chromatography in 1000 patients. Compared with laboratory testing for opioids and illicit drugs, immunoassay in-office testing has high specificity and agreement but variable sensitivity, which demonstrates the value of immunoassay drug testing; however, a cautious approach is advocated. Agreement for prescribed opioids was high with the index test (80.4%). The reference test of opioids improved the accuracy by 8.9% from 80.4% to 89.3%. Urine drug testing should not be confrontational, but rather both clinicians and patients should view UDT like any other laboratory test. Because UDT may support or trigger the clinician’s suspicions about aberrant drug-taking, it is information that the clinician must view with other factors to see “the whole picture.” The clinician must be aware of the limitations of these tests (e.g., low sensitivity of immunoassay for semisynthetic and synthetic opioids). Confirmatory tests should be specifically requested. If the purpose of testing is to find unprescribed or illicit drug use, combination techniques such as gas chromatography and mass spectrometry (GC/MS) or high-performance liquid chromatography (HPLC) are most specific for identifying individual drugs or their metabolites.¹²

Caveats to the use of UDT include the following:

1. 
   

   Ensure the proper collection, handling, and documentation of the urine specimen.

   
   
2. 
   

   Be knowledgeable regarding interpretation of UDT results.

   
   
3. 
   

   Know specifically what your patient consumed and when it was consumed prior to the urine collection.

   
   
4. 
   

   Know what you are looking for and what you will do when various results come back.

One of the most common urinary drug screens involves fluorescence polarization immunoassay, which detects the “federal five” of marijuana metabolite (delta-9-THC), cocaine metabolite (benzoylecgonine), opiates, phencyclidine (PCP), and amphetamines/methamphetamines. The test has a relatively low sensitivity for semisynthetic and synthetic opioids (e.g., hydrocodone, oxycodone, fentanyl). Therefore, if the test on the patient’s urine is negative for the presence of one of these drugs, it does not exclude use. Furthermore, even if the test is positive for a specific drug, a confirmatory test should follow. The confirmatory UDT is based on principles of GC/MS or HPLC. The gold standard is considered to be the GC/MS. The expanded “federal ten” also tests for methadone, propoxyphene (no longer available), methaqualone, benzodiazepines, and barbiturates.

High-performance liquid chromatography (HPLC) uses a stationary phase (usually hydrophobic saturated carbon chains) contained in a stainless steel column in order to help separate, identify, and quantify compounds based on their particular polarities and interactions with the column’s stationary phase. Other components may involve a pump providing high pressure to move the mobile phase (e.g. buffered organic solvent mixture) and a detector. The analyte retention times are variable and may be affected by the strength of interactions with the stationary phase as well as the ionic strength and flow rate of the mobile phase. When coupled with multiple mass spectrometers [MS] (e.g., HPLC/MS/MS), these techniques may be particularly effective to identify compounds in UDT.

Care must be taken in the collection of the urine specimen and in ensuring that the “handling chain”/“chain of custody process” to the lab is executed and documented properly. The collection facility should be a private area with no sink basin or access to water/liquids, and the toilet should have pigmented toilet water (e.g., blue). Measurements of urinary creatinine, pH, specific gravity, and temperature should also be ordered and recorded to assist with results interpretation and to increase specimen reliability. To confirm reliability and authenticity of the urine sample, values for each of the variables should be within the following limits:

• 
  

  Temperature (within 4 minutes of voiding): 90°F to 100°F

  
  
• 
  

  Urinary pH: 4.5 to 8.0

  
  
• 
  

  Urinary creatinine: 20 mg/dL

Additionally, Specimen Validity Testing (SVT) to determine if adulterants/foreign substances were added to urine or if the specimen was substituted should occur (e.g., testing for nitrite, pyridine, glutaraldehyde, bleach, soap). Adulterated specimens may be suspected if nitrate is ≥500 mcg/mL, or pH is ≥11, or exogenous substances are present, or substances are present at significantly higher concentrations than normal physiologic concentration (e.g., chromium + 6 in significant supraphysiologic concentrations).

Appropriate interpretation of UDT is vitally important. Clinicians should appreciate the potential metabolites of the various opioids that their patients are taking (Table 71-1). Reisfield and colleagues concluded that family physicians who ordered UDT to monitor patients with persistent pain on COT were not proficient in their interpretation.¹³ Nafziger and Bertino described the following factors that may affect the results of UDT: cutoff selection; pharmacogenetics [ultra-rapid metabolizers]; laboratory technology; and subversion/adulteration of the urine specimen¹⁴ (Table 71-2).