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Past Medical History (per EMR)
Pain, hand
Wrist drop
Headache
Chronic pain: opioid-requiring
Chronic pain opioid: 2 week refill
Hypertension
Pancreatitis, chronic
Dependence, continuous; MS Contin for chronic pancreatitis
Degenerative joint disease, hands
Pelvic pain
Peripheral neuropathy
Tobacco abuse
Migraine, classical
Depression

Social History (per EMR)
Tobacco: Current smoker, less than 1 pack per day.
Alcohol: Rarely.
Illicit drugs: Marijuana.

Medication List
Dilaudid 8 mg tabs (hydromorphone HCL) 1-4 tabs every 4 hours as needed for pain (max 8 day)
MS Contin 60 mg tb12 (morphine sulfate) 1 tablet 3 times a day
Atenolol 50 mg tabs (atenolol) take 1 tablet by mouth daily
Norvasc 10 mg tabs (amlodipine besylate) take 1 tablet by mouth daily
Lyrica 150 mg caps (pregabalin) 1 tab twice a day
Evista 60 mg tabs (raloxifene HCL) take 1 tablet by mouth once daily
Cyclobenzaprine hcl 10 mg tabs (cyclobenzaprine HCL) once a day as needed for muscle spasms
Omeprazole 20 mg cpdr (omeprazole) take 1 capsule by mouth twice daily
Ranitidine hcl 150 mg tabs (ranitidine HCL) take 1 tablet at bedtime

Laboratory data:

Assessment:

Methadone
The urine immunoassay drug screen performed on the specimen collected on (DATE) tested presumptively positive for methadone. Definitive testing by LC-MS/MS (liquid chromatography-tandem mass spectrometry) identified both methadone (2500 ng/mL) and the primary metabolite EDDP (12000 ng/mL), confirming in vivo metabolism of methadone. Methadone is a synthetic opioid used to treat opioid abuse and withdrawal symptoms as well as for chronic pain. Methadone has a long half-life (15–55 hours) and is detectable in urine for several days after the final dose.

Opiates
The in-house urine immunoassay drug screen performed on the specimen collected on (DATE) tested presumptively positive for opiates. This immunoassay is designed to cross-react with the naturally occurring opiates codeine and morphine, producing a positive result at concentrations of ≥150 ng/mL and ≥300 ng/mL, respectively. Definitive testing by LC-MS/MS identified morphine (>15000 ng/mL) and hydromorphone (1700 ng/mL) only. No other common opiates/opioids were detected (ie, codeine, hydrocodone, norhydrocodone, oxycodone, oxymorphone, noroxycodone).

Morphine can be found in urine following administration of morphine itself (eg, MS Contin) or as the metabolite of either codeine or heroin. The concentration of morphine found in the urine (>15000 ng/mL) is consistent with administration of morphine prior to the urine collection. Morphine has a half-life of 2 to 7 hours, and can be detected in the urine up to 2 to 3 days after the last dose. In light of the unexpected methadone immunoassay result and elevated morphine concentration, the urine sample collected on (DATE) was sent for definitive testing for heroin metabolites. The result of this analysis did not detect the heroin metabolite 6-acetylmorphine (6-AM). However, the absence of 6-AM does not rule out heroin use. Heroin, or diacetylmorphine, has an extremely short half-life (1-4 minutes) and is rapidly metabolized to 6-AM. 6-AM is also metabolized relatively quickly (3-52 minutes) to morphine.

Hydromorphone is a semisynthetic opioid (sold as Dilaudid) and is a major metabolite of hydrocodone (Vicodin) and a minor metabolite of morphine. Hydromorphone in the urine is consistent with administration of Dilaudid prior to the urine collection. However, given the concentration of hydromorphone was 1700 ng/mL, it is not possible to exclude that the hydromorphone is a metabolite of morphine. Hydromorphone has a plasma half-life of up to 9 hours and can be detected in urine 2 to 3 days after the last dose. Detection in the urine is dependent on both elimination patterns and the hydration status of the patient.

Note: Definitive testing did not include all well-characterized opiates/opioids (and as yet any newly emerging designer opioids) that may cross-react with the in-house opiates class immunoassay to produce a positive result. As such, it is not possible to exclude administration of other opiates/opioids not specifically tested for here.

Buprenorphine
The in-house urine immunoassay drug screen performed on the specimen collected on (DATE) tested presumptively positive for buprenorphine. Definitive testing LC-MS/MS did not detect either buprenorphine or the primary metabolite norbuprenorphine. The buprenorphine immunoassay is not expected to cross-react with other individual opiates/opioids taken by this patient at low concentrations (ie, hydromorphone, methadone, morphine). However, when taken in combination, or at high concentrations (such as morphine or codeine), these opiates may be sufficient to produce a positive buprenorphine result. These findings suggest that the positive buprenorphine immunoassay result is a false positive. Buprenorphine is a semisynthetic opioid sold under the trade names Subutex (buprenorphine), Suboxone (buprenorphine and naloxone combination) and Butrans (transdermal patch), marketed for the treatment of opioid addiction. Due to its powerful analgesic and euphoric effects, buprenorphine may be abused or substituted for heroin or other opioids.

THC-Cannabinoids
The in-house urine immunoassay drug screen performed on the specimen collected on (DATE) tested presumptively positive for THC-cannabinoids. Definitive testing was not performed. The in-house immunoassay detects metabolites of delta-9-tetra-hydrocannabinol (THC), the primary psychoactive component of marijuana. The patient’s urine may be positive for 2 to 7 days after use or for up to 1 month in chronic smokers.

Conclusion
In conclusion, the patient’s toxicology results are not consistent with the prescribed medications. The positive immunoassay methadone result, as confirmed by LC-MS/MS, indicates administration of methadone prior to the urine collection. Definitive testing for opiates identified morphine and hydromorphone, consistent with the patient’s prescriptions for MS Contin and Dilaudid, respectively, although one cannot exclude the possibility of hydromorphone as a morphine metabolite.

Definitive testing for buprenorphine was negative, indicating that the urine immunoassay buprenorphine result was a false positive, most likely attributable to cross-reactivity of the combined effect of the other opioids present in the urine. Definitive testing for THC-cannabinoids was not performed. Further investigation into the patient’s possible use of unprescribed drugs should be explored.

Pathologist’s Name: ___________________, MD

Department of Pathology and Laboratory Medicine

DATE and TIME STAMP

Pearls

• With urine drug immunoassays, it is important to be familiar with cross-reactivity of both related and unrelated drugs, keeping in mind that a positive result may be attributable to the presence of one (or more than one) drug in the sample. An up-to-date and complete medication list of both prescribed and unprescribed drugs is essential.
• The absence of 6-AM in definitive testing does not exclude the possibility of heroin use. As heroin is metabolized rapidly to 6-AM and then relatively quickly to morphine, the absence of 6-AM may be a consequence of the time interval between last heroin use and urine collection. Similarly, the presence of morphine is not indicative of heroin use, as it may be the result of use of morphine-containing drugs, or as the metabolite of codeine, or consumption of contaminated poppy seeds. Avoid insinuation and overinterpretation regarding possible heroin use whenever 6-AM is not detected with definitive testing. Specific immunoassays for 6-AM are available.
• High concentrations of morphine (and codeine) can cross-react with buprenorphine immunoassays and produce a positive result.