Opiates

The term opiates refer to naturally occurring alkaloids (morphine and codeine) obtained from the opium poppy, Papaver somniferum, as well as the semi-synthetic alkaloids (e.g., buprenorphine, dihydrocodeine, heroin, hydrocodone, hydromor-phone, levophanol, oxycodone, and oxymorphone). The term opioids refers to a group of compounds that have pharmacological properties similar to morphine and affinity toward the opioid receptors. Opioids include not only the opiates, but also synthetic compounds that are structurally unrelated to morphine: fentanyl, meperidine, methadone, pentazocine, propoxyphene, and tramadol. Thus, all opiates are opioids but the reverse is not true. The opiate immunoassays are designed to detect morphine and codeine as the target analytes, and the cross-reactivity with other opiates varies with the assays. For example, most opiate assays have high cross-reactivity for hydrocodone and hydromorphone to detect their presence, much lower reactivity for oxycodone for reliable detection, and negligible reactivity for buprenorphine. With the recent popularity of oxycodone as a drug of abuse and the introduction of buprenorphine in the US market for treatment of heroin dependency, immunoassays specific for these two opiates are now available. Opiate assays have no reactivity with the opioids that are not opiates. Individual immunoassays developed to detect specific opioids are available for fentanyl, methadone (and EDDP), and propoxyphene. Clearly, consultation with manufacturer's package insert for assay immunospecificity is crucial to understanding the applicability and limitations of opiate assays for different drug testing programs.

It is important to understand the metabolism of the opiates for proper interpretation, particularly of the minor metabolites: approximately 10% of codeine is metabolized to morphine; hydromorphone and dihydrocodeine are minor metabolites of hydrocodone; oxymorphone is a metabolite of oxycodone; and hydrocodone and hydromorphone are minor metabolites found in the presence of very high codeine and morphine concentrations, respectively (38,39). Otherwise, detection of a minor metabolite (e.g., hydro-

morphone) in addition to the prescribed medication (morphine) may be mistakenly interpreted as illicit drug use.

Poppy seeds may contain morphine and codeine. Therefore, consumption of poppy seed food may result in urinary presence of morphine and codeine in concentrations exceeding the 300 ng/ml cutoff. ElSohly and co-workers (40) have proposed guidelines to interpret urinary morphine and codeine results as to the source of the morphine. Alternatively, the initial test cutoff has been raised to 2000 ng/ml, a level sufficiently higher than those seen following ingestion of contaminated poppy seeds. An intermediary metabolite of heroin (diacetylmorphine) is 6-monoacetylmorphine (6-AM). Thus, the detection of 6-AM in the presence of morphine in urine points to heroin as the source of morphine. As 6-AM has a very narrow window of detection (6-12 h), its brief presence after heroin use can be missed. Recent reports have indicated that it is possible to have detectable 6-AM even if morphine concentration is below the 300 ng/ml threshold (41). Therefore, a testing program using an opiate assay as the first test will miss these patients, hence, the proposal to use both opiates and 6-AM assays to screen for heroin abuse. The opiates cutoff used in workplace drug testing (2000 ng/ml) may be inappropriately high for clinical or postmortem toxicological testing for possible heroin use as many cases that had documented 6-AM had total opiates <2000 ng/ml (42).

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