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16 Articles in Volume 19, Issue #2
Analgesics of the Future: Inside the Potential of Glial Cell Modulators
APPs as Leaders in Pain Management
Cases in Urine Drug Monitoring Interpretation: How to Stay in Control (Part 1)
Complex Chronic Pain Disorders
Efficacy of Chiropractic Care for Back Pain: A Clinical Summary
Hydrodissection for the Treatment of Abdominal Pain Caused by Post-Operative Adhesions
Letters: The Word "Catastrophizing;" AIPM Ceases Operations; Patient Questions
Management of Severe Radiculopathy in a Pregnant Patient
Managing Pain in Adults with Intellectual Disabilities
Pain in the Courtroom: An Excerpt
Q&A with Howard L. Fields: How Patients’ Expectations May Control Pain
Special Report: CGRP Monoclonal Antibodies for Chronic Migraine
The Management of Chronic Overlapping Pain Conditions
Vibration for Chronic Pain
What are the dangers of loperamide abuse?
When Patient Education Fails to Improve Outcomes: A Low Back Pain Case

Cases in Urine Drug Monitoring Interpretation: How to Stay in Control (Part 1)

Basic principles in urine drug monitoring (UDM) are reviewed and applied to a patient testing positive for oxycodone and amphetamine.
Pages 41; 43-44

This first case in a new series focuses on the differences between presumptive and definitive urine toxicology analysis with a focus on the amphetamine immunoassay.


RR is a 58-year-old male with spinal stenosis prescribed oxycodone SA 20 mg PO Q12H which, for this patient, provides analgesic and functional benefit without adverse effects. The patient has PMH significant for gastroesophageal reflux disease (GERD) and depression. Other medications include ranitidine for GERD, bupropion for smoking cessation, and quetiapine for sleep. The patient is due for his yearly urine drug monitoring (UDM).

The patient’s immunoassay results return as shown:

Role of Urine Drug Monitoring

Universal risk-mitigation strategies for the use of chronic opioid therapy (COT) include urine drug monitoring. The goal of UDM is to monitor patient compliance with prescribed medications and avoidance of illicit or unprescribed substances.1 The CDC Guideline for Prescribing Opioids for Chronic Pain recommends UDM prior to initiation of COT and at least annually during continuation of COT.2 Consensus recommendations on UDM suggest repeat UDM frequency commensurate with patient risk.3 To determine risk, the patient’s history, validated tools for aberrant medication-taking behavior, opioid misuse, opioid use disorder, and respiratory depression/overdose should all be considered3 (see Table I). Ideally, UDM is employed on a random basis though this may not always be feasible.

Types of UDM

Initial UDM is performed via screening immunoassay and is considered a presumptive test. Immunoassays use antibody-antigen complexes to identify the presence of substances. A certain threshold (cut-off) must be met to be considered positive and depends on the window of detection of the substance being tested.4

Definitive testing involves gas or liquid chromatography combined with mass spectrometry. With chromatography, the substances in the urine sample are separated based on interaction with the medium (liquid or gas) most often by polarity.5 Typically, chromatography is reserved to confirm initial results though it can be used as both initial and confirmatory situations.3,5 Consensus recommendations on UDM recommend definitive testing at baseline for chronic pain patients prescribed opioids unless facility or payor rules require an initial immunoassay.3 See Table II for the differences between immunoassay and chromatography testing (Note: Part 2 of this series will go into further detail on immunoassay testing for opiates). Clinical decisions to alter the treatment plan should be made upon definitive testing.

Sample Validity

Several methods are used to determine whether a urine sample is valid including temperature, pH, specific gravity, and urine creatinine. There are tests available to determine the presence of adulterants as well6 (see Table III).

Cut-off Concentrations

Cut-off concentrations have been established by the federal government for workplace drug testing4 (see Table IV). Values below the cut-off are reported as negative. These cut-offs were made to prevent false positives but actually increase the possibility of false negatives.4 Because some of these cut-offs are set fairly high, there is a limited role in clinical use.6,7 Clinicians should review the cut-off concentrations of the test used in the state where they practice.

Window of Detection

The length of time a substance or metabolite can be detected is found as the window of detection or detection time. Several factors determine the window of detection and include chemical properties of the substances being tested, individual metabolism rates and excretion routes, route of administration, frequency of use, and amount of substance used, sensitivity/specificity of the test, cut-off concentrations, individual patient factors (eg, health, diet, weight, gender, fluid intake, pharmacogenomic profile), and the biological specimen tested.6

The window of detection for single doses of amphetamines and methamphetamines is around 24 hours. Chronic and high dose use may lead to positive results for 2 to 4 days after last use. Methylenedioxyamphetamine (MDA), methylenedioxymethamphetamine (MDMA), and methylenedioxyethylmethamphetamine (MDEA) are able to be detected for 1 to 2 days.6

(Source: 123RF)

Amphetamine Immunoassay

The amphetamine immunoassay targets amphetamine, methamphetamine, and some illicit anaglogs.4 Amphetamines and methamphetamines are available as prescription medications. There are two groups of amphetamine immunoassay tests: one that only focuses on amphetamine and methamphetamine; and one that also targets “designer amphetamines” (MDA, MDMA, MDEA), and other sympathomimetic amines with the catecholamine ring structure.6 Some medications metabolize to methamphetamine or amphetamine, one exception being selegiline ( N-desmethylselegiline and l-methamphetamine L-amphetamine).6 Methamphetamine is an enantiomer, and the d-isomer has high abuse potential.

Previously, an over-the-counter nasal inhaler containing l-amphetamine was available; however, this has been removed from the market. Another example no longer available in the US is ephedra, a naturally occurring plan similar to several neuroamines, including methamphetamine. Kratom is also a naturally occurring plant-derived drug which at low doses blocks reuptake of neuroamines and at higher doses has opioid partial agonist properties. Although it has been outlawed in many states, kratom is still readily available for purchase in most and is orderable on the Internet. With increased use of kratom, there is a higher likelihood of serotonin syndrome and other drug interactions with sympathomimetics. Moreover, it has been attributed to methadone false positive via immunoassay.

The main issue with the amphetamine immunoassay is the high rate of false positive from cross-reactivity (see Table V). Therefore, unless a patient is prescribed amphetamines, a positive amphetamine on immunoassay should be sent for definitive testing.6

Return to Patient Case

The patient’s UDM is positive for oxycodone and amphetamine. The positive oxycodone is expected since the patient is prescribed oxycodone. The methadone may be a false positive from several sources, two of which include kratom or quetiapine, the latter of which was prescribed for this patient. (A future case in this series will focus on UDM considerations for opioids.) The positive amphetamine is not expected. Knowing that the amphetamine immunoassay is highly cross-reactive and that clinical decisions should be made upon definitive testing; the urine sample is sent for GC-MS testing. Of note, the patient is currently prescribed ranitidine and bupropion that are listed as possible false positives on the amphetamine immunoassay. Even knowing these are common cross-reactants, it is important to order additional testing to make sure it is a false positive and not due to the presence of methamphetamine/amphetamine.

Results of GC-MS testing were shown as follows: Bupropion, Oxycodone, Noroxycodone, and Oxymorphone. Based on the definitive testing, no further action is needed as the results show expected prescribed medications and their metabolites and no unexpected substances are present.


Urine drug monitoring is an important risk-mitigation strategy recommended in treatment practice guidelines for patients prescribed chronic opioid therapy for chronic pain. Frequency of UDM is determined by patient risk. Key considerations should be applied, including test type, specimen validity, cut-off concentrations, and detection window, as well the amphetamine immunoassay with regard to its major pitfall: false positives.


Editor's Note: This article was updated after print publication.

Last updated on: August 2, 2019
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Cases in Urine Drug Monitoring Interpretation: How to Stay in Control (Part 2)
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