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14 Articles in Volume 9, Issue #7
Anomalous Opiate Detection in Compliance Monitoring
Anticipating Biotechnological Trends in Pain Care
Continuous Lumbar Epidural Infusion of Steroid
Disordered Sacroiliac Joint Pain
Efficacy of Stimulants in Migraineurs with Comorbidities
Hand Tremor with Dental Medicine Implications
Helping Patients Understand the
Non-surgical Spinal Decompression (NSSD)
Pain Management in Nursing Homes and Hospice Care
Patients Who Require Ultra-high Opioid Doses
Relief of Symptoms Associated with Peripheral Neuropathy
Share the Risk Pain Management in a Dedicated Facility
The Multi-disciplinary Pain Medicine Fellowship
Thermal Imaging Guided Laser Therapy: Part 2

Anomalous Opiate Detection in Compliance Monitoring

There are multiple variables outside of laboratory testing to consider when interpreting a patient’s test results and deciding whether or not they are compliant with their medication.

The progression of urine drug testing to include cut-off levels and drug panels appropriate for compliance monitoring has revolutionized the practice of pain management. Compliance monitoring enables physicians to offer more effective patient care by identifying drug misuse or addiction, verifying diagnoses, and determining potential cross-reactants among prescribed medications. It also offers a level of protection from legal liability for physicians and their clinics by providing proof of due diligence that they are evaluating patients on a regular basis.

However, like all medical testing, compliance monitoring has its limitations. Even when state-of-the-art lab equipment is used from the screen to the confirmation, you can only glean so much from an instrument. Oftentimes there are outside factors that must be taken into account before making a judgment based on a test result—specifically when dealing with patients who are treated with relatively high doses of opiates.

The Practice of Testing for Compliance

Processes used for determining compliance can differ between laboratories and depend on instrumentation, chain-of-custody procedures, and types of specimens received. At AIT Laboratories, a full-service reference laboratory serving compliance monitoring, forensic, clinical, and pharmaceutical clients, the process comprises an initial immunoassay screen and a quantitative confirmation on all positive urine specimens. Positive specimens are confirmed and quantified by GC/MS or LC/MS. Validity markers such as oxidants, specific gravity, pH, and creatinine determination also give care providers additional information regarding potential specimen tampering.

Compliance monitoring requires lower cut-off levels that are typically achieved using state-of-the-art instrumentation available only in a laboratory setting.1 It also requires more advanced methodology. One method well-suited for compliance monitoring is LC/MS/MS, which separates individual components of a complex mixture and generates a unique “chemical fingerprint” for each drug. This enables positive identification and quantification of substances at very low levels (potentially as low as 10ng/mL for opiates) and provides high specimen throughput (and thus reduced turn-around time) without compromising the quality of results.

No matter how impressive the equipment, it is important to note that even the most sophisticated instruments can only determine a compound’s presence and its concentration. The origin of the drug ingested, on the other hand, is often beyond the scope of information that can be provided by a laboratory. Additional information may be required before a caregiver can make an informed decision regarding whether a patient is compliant or non-compliant. This is especially true when dealing with patients who are following a treatment plan involving high doses of opiates. The high sensitivity of current analytical methods allows identification of low drug concentrations previously undetected using less advanced instrumentation. Toxicologists at AIT have encountered three important opiate testing anomalies that we believe require careful consideration.

Possible Explanations for the Presence of Previously Undetectable Opiates at Low Concentrations

The Presence of Morphine When Morphine Is Not Prescribed

Poppy seeds originate from the poppy plant and contain morphine, codeine, and thebaine. Suppliers of poppy seeds strive to wash the seeds clean of these opiates; however, the washing process is typically not sufficient to remove all of the drug. As such, individuals who ingest poppy seeds may test positive in the urine for low concentrations of morphine (codeine and thebaine are present at significantly lower levels in the poppy seeds and usually go undetected in the urine).

The detection of morphine in the urine is considered a “true positive” because morphine is actually causing the positive result but its origin remains in question. Concentrations as high as 4,500 ng/mL can be detected in urine following poppy seed ingestion.2 This is obviously dependent upon the extent of ingestion and the timing between ingestion and specimen collection.

The Presence of Codeine When Prescribing Morphine

In addition to morphine, the poppy plant also contains codeine and is difficult to remove during the pharmaceutical manu-facturing process for morphine. Therefore, pharmaceutical-grade morphine formulations typically contain low levels of codeine as an impurity and may result in low codeine concentrations in the urine from patients who have been prescribed relatively high doses of morphine for extended periods of time.3 While codeine detected in such cases is considered a “true positive,” it may have resulted from urinary accumulation after prolonged, high-dose morphine treatment.

The Presence of Hydrocodone When Prescribing Oxycodone

Similar to the presence of codeine as an impurity in morphine, the same phenomenon could explain the presence of hydrocodone in the urine of patients who are prescribed high doses of oxycodone for extended periods of time. AIT has determined hydrocodone in multiple urine specimens collected from purportedly compliant patients taking high doses of oxycodone. Urinary hydrocodone concentrations were typically less than 100ng/mL, its metabolite hydromorphone is absent, and high concentrations of oxycodone were present. In addition, we tested various oxycodone formulations in which low levels of hydrocodone were detected. While this does not preclude the possibility of hydrocodone being an abnormal and unexpected metabolite, it provides a possible explanation for positive hydrocodone in patients who are believed not to have taken the drug.

“The detection of morphine in the urine is considered a “true positive” because morphine is actually causing the positive result but its origin remains in question.”


Compliance monitoring is designed to detect the presence or absence of prescribed and non-prescribed medications and illicit substances. It is not intended to be a definitive resource for pinpointing where a drug came from or how it was manufactured. There are multiple variables outside of laboratory testing to consider when interpreting a patient’s test results and deciding whether or not they are compliant with their medication.

Last updated on: January 6, 2012
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