by Amanda J. Jenkins, PhD
Scientific Director, Toxicology
Opioids and other medications (non-opioid analgesics, benzodiazepines, antidepressants, anticonvulsants, muscle relaxants) are prescribed to treat chronic pain of non-cancer origin.1
Ongoing monitoring of these patients is important to ensure safe and effective therapy. Drug testing is one tool utilized to identify patients who qualify for therapy and then to evaluate the continued effectiveness of pain relief; assess the potential for misuse, addiction or diversion; and ensure adherence to an agreed upon treatment plan. Urine is typically the specimen of choice since it is easy to collect, drugs/metabolites are generally detected at higher concentrations and for a longer period of time compared with blood/serum/plasma. The traditional clinical role of urine drug testing is to confirm a physician’s diagnosis or identify a toxin in the absence of a differential diagnosis, eg. to support treatment decisions in an emergency setting.
It is expected that the majority of patients will test negative when testing for toxins. This type of testing in a hospital or urgent care facility may be limited to illicit drugs of abuse such as heroin, MDMA (ecstasy) and cocaine. When utilized in the pain management arena, periodic urine drug testing is utilized to monitor compliance with prescribed medications, in addition to identifying use of non-prescribed, and illegal drugs. The majority of these patients will test positive for prescribed and non-prescribed medications. Therefore, the objectives of periodic urine drug tests are:
To detect prescribed drug compliance:
- Identify use of prescribed medications
- Identify use of undisclosed drugs
To discourage drug misuse:
- Decrease potential of abuse
- Decrease potential for diversion
Testing methods
Urine drug testing typically utilizes a presumptive initial screening test, usually immunoassay (IA), which may be laboratory based or a point-of-care device. Immunoassays are available for panels as well as individually orderable drug classes, e.g. benzodiazepines, methadone. Results obtained will depend upon the screening method. Results obtained will depend upon the screening method and the sensitivity and specificity.
Testing may be ordered in multi-drug panels such as:
- Opiates: Morphine, Codeine, 6-Acetylmorphine
- Opioids: Fentanyl, Buprenorphine, Methadone, Tramadol, Oxycodone, Oxymorphone, Hydrocodone, Hydromorphone, Meperidine, Tapentadol
- Benzodiazepines
- Muscle Relaxants: Carisoprodol
- Cannabinoids
- Cocaine (Metabolite)
- Amphetamine/Methamphetamine/MDMA
- Barbiturates: Phenobarbital, Butalbital
- Phencyclidine
Typical IAs for benzodiazepines demonstrate low cross reactivity for lorazepam and clonazepam. Laboratory-developed enhancements, such as hydrolyzing the specimen to cleave the glucuronide bond and modifying the calibrator, results in improved detectability of these drugs. Similar modifications to the opiate IA enables lower concentrations to be detected.
The scope of testing is not standardized within the industry. Testing should be tailored to the individual patient. Factors to consider when making testing decisions should include prescribed controlled medications, substances endemic to a particular region, with more comprehensive testing considered for patients with substance misuse/abuse issues. Additional substances not included in the list above which may be targeted include ethanol or ethyl glucuronide and ethyl sulfate, gabapentin, pregabalin, tricyclic antidepressants, zolpidem, methylphenidate or its metabolite ritalinic acid, and tests to determine specimen validity such as pH, creatinine, oxidants, and specific gravity. Aspects of urine drug testing which should be individualized include testing frequency, schedule, composition of panels, and type of collection.2 According to the American Society of Addiction Medicine (ASAM), the frequency of testing should be matched to patient risk.2 In addition, patients should not know when and for which drugs they will be tested. Lastly, urine collection in pain management is typically unwitnessed. Since specimen substitution and adulteration do occur, it is reasonable for physicians to develop a collection protocol which maximizes specimen integrity while balancing concerns of privacy. A secondary test using definitive mass spectrometry techniques is utilized to provide specific drug identification which may be qualitative or quantitative. These definitive tests are used to confirm presumptive tests, to rule out false positive presumptive results and when presumptive drug class tests are not available.
The decision-making process of whether to order confirmation testing should include:
- Are the presumptive results inconsistent with clinical expectations or the pharmacy record?
- Does the presumptive test detect the drug(s) of interest?
- Is definitive identification of a drug required (applicable mainly to IA drug class tests?)
- Are quantitative results required?
Opiate and benzodiazepine IAs may not have sufficient sensitivity to detect low dose applications. In addition, some amphetamine IAs may produce positive results for over the counter medications. In instances where screening results are inconsistent with prescribed medications and/or a patient drug use self-report, confirmation testing should be performed. Quantitation of drugs in urine should not be used to estimate dose, or compliance with a specific dosing regimen. Urine drug levels are dependent upon multiple factors including the physicochemical characteristics of each drug, the dosing regimen and formulation, route of administration, hydration status and urine pH in addition to renal and liver function. Knowledge of urine drug levels may be helpful to decide if the presence is consistent with the metabolic profile or if it may be a process impurity or suggests the use of more than one drug. Designer drugs such as substituted cathinones and synthetic cannabinoids are not detected by these methods and, therefore, the clinician should contact the toxicologist at the laboratory to identify the most appropriate testing.
Interpretation
Interpreting urine drug testing results may pose challenges. Knowledge of the limitations of testing—cutoff or threshold concentrations, drug targets and cross reactivities is important. Knowledge of metabolic patterns, and the influence of pharmacokinetics is necessary for appropriate interpretation of results. Unexpected results require investigation to include the patient, the specimen, and the testing. General factors to consider in interpreting urine drug testing results are listed below:1
Drug not detected due to:
- Drug not taken/administered
- Drug taken incorrectly (decreased dose or frequency)
- Variable drug delivery—drug not absorbed
- Accelerated metabolism, elimination
- Drug-drug interaction
- Specimen collected outside detection window
- Specimen diluted, substituted, adulterated
- Test not designed to detect drug or low sensitivity
- Clinic or laboratory error
Drug detected due to:
- Drug was taken/administered
- Drug detected is a process impurity
- Drug detected is an expected metabolite of a prescribed drug
- Incorrect prescription filled
- Drug obtained elsewhere
- Drug added directly to specimen
- Result is a false positive (for IA screens)
- Clinic or laboratory error
Published date: July 14, 2017
