Pitfalls with Urine DrugTesting UDT

The opiate immunoassay screens were designed to detect heroin use, not adherence to a therapeutic opioid regimen. These immunoassays use monoclonal antibodies to detect morphine and codeine - heroin is rapidly metabolized to 6-monoacetylmorphine (6-MAM), and then to morphine [59].

For patients not prescribed morphine, presence of morphine in urine is often incorrectly assumed to be indicative of heroin use. A morphine-positive UDT may also result from codeine, from morphine use or misuse, and detectable levels are possible from morphine in foodstuffs (e.g., poppy seeds in breads/confectionery) [59, 69, 72]. However, performing opiate immunoassays at the federally mandated level of 2000 ng/mL, which was established in 1998, should eliminate nearly all positive results due to morphine from foodstuffs [59]. Only specific detection of 6-MAM by gas chromatography/mass spectrometry (GC/MS) is proof of heroin intake [59]. In addition, street heroin may be contaminated with codeine [59].

In the clinical setting when monitoring patients' adherence to a treatment plan, it is important that the lower cutoff level of 300 ng/mL be used for both screening and confirmation [62].

The next figure shows some of the pathways by which opioids are metabolized. Heroin is metabolized to 6-monoacetylmorphine (6-MAM) and then to morphine (Figure V-9). Heroin itself is rarely recovered from urine [62]. Codeine is metabolized to morphine, but not vice versa, so both substances may occur in urine following the use of codeine [62]. Hydrocodone can also be produced as a minor metabolite of codeine, and hydrocodone can be metabolized to small quantities of hydromorphone. Clinical experience suggests that morphine may be metabolized to produce small amounts of hydromorphone, possibly through keto-enol tautomer-ization [62, 73]. Therefore, these pathways may explain the presence of apparently unprescribed drugs. However, at no time should a minor metabolite be in excess of its parent - this would be consistent with use of the second drug [62].

As with any unexpected test results, it is important to clarify the interpretation with someone who is knowledgeable in clinical toxicology.

Also, most semisynthetic and synthetic opioids will not result in morphine or codeine appearing in the urine and are therefore not reliably detected by commonly used opiate immunoassays, even at high concentrations. Nevertheless, cross-reactivity can occur, causing positive results. However, gas chromatography/mass spectrometry (GC/MS) can reliably identify all opioids that are present [59]. If the purpose behind the test is to document the presence of a prescribed medication, such as oxycodone, hydromorphone, or hydrocodone (Table V-6), the laboratory should be informed of this and perform specific-drug identification by GC/MS in addition

Figure V-9. Not comprehensive pathways, that may explain the presence of apparently unprescribed drugs 6-MAM = 6-monoacetylmorphine, an intermediate metabolite of heroin
Table V-6. Summary of semisynthetic and synthetic opioids not reliably detected by commonly used screens

Natural (from opium)

Semisynthetic (opium-derived)

synthetic (man-made)

• codeine

• hydrocodone

• meperidine

• morphine

• oxycodone

• fentanyl

• thebaine

• hydromorphone

• sufentanil

• oxymorphone

• propoxyphene

• buprenorphine

• methadone

to a routine immunoassay screen [62]. It is also recommended that the laboratory be instructed to remove the reporting threshold (cut-off concentration) so that the presence of lower concentrations of the prescribed drug can be documented. This will reduce the risk of missing a drug that is, in fact, present.

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