Published: Journal of Analytical Toxicology, ISSN 0146-4760, Volume 25, Number 7, October, pp. 657-658

LETTER TO THE EDITOR: Applicability of Opiate Cutoffs to Opiate Intoxication Cases
Karla A. Moore[1], Joseph Addison[1], Barry Levine[1],[2], and John E. Smialek[2]
[1]Division of Forensic Toxicology, Armed Forces Institute of Pathology, Washington, D.C. 20306-6000 and [2]Office of the Chief Medical Examiner, State of Maryland, 111 Penn St., Baltimore, Maryland 21201

To the Editor:
As a way of combating drug abuse in the military and in the workplace, the Departments of Defense (DOD) and Health and Human Services (HHS) promulgated guidelines for the testing of urine specimens for a number of drug classes, including opiates, specifically morphine and codeine. In the 1980s, an immunoassay screening cutoff of 300 ng/mL was established by both DOD and HHS. HHS also permitted a screening cutoff of 25 ng/mL if the immunoassay tested specifically for free morphine. Moreover, both departments set the confirmation cutoff concentration at 300 ng/mL total morphine or 300 ng/mL codeine. The use of these cutoff concentrations led to a number of problems. One was that a large number of cases were identified as opiate-positive specimens but resulted from the legal use of codeine. A more serious concern was the “poppy seed” issue, that is, individuals eating or claiming to eat food products containing poppy seeds were testing positive for opiates. In response to these issues, both DOD and HHS changed the cutoff concentrations for opiates. Specifically, DOD and HHS chose an opiate screening cutoff concentration of 2000 ng/mL and a confirmation cutoff concentration for total morphine of either 2000 ng/mL (HHS) or 4000 ng/mL (DOD). The confirmation cutoff was set at 2000 ng/mL for codeine. In addition, a specific marker of heroin use, 6-acetylmorphine (6-AM), was added to the confirmation testing. Specimens tested under HHS guidelines are tested for 6-AM if the total morphine concentrations exceeded 2000 ng/mL. HHS uses a 10-ng/mL cutoff for 6-AM. For a specimen to be positive for “OPIATES,” the urine total morphine concentration and the 6-AM concentrations must be at or above the respective cutoffs. All DOD specimens confirming positive for morphine are tested for 6-AM at a cutoff of 10 ng/mL. Any specimen testing positive for 6-AM at that cutoff is positive for “HEROIN;” otherwise, the specimen is reported as positive for “MORPHINE.”

Deaths due to opiate intoxication remain a problem in the United States. As a result, the testing of postmortem specimens for opiates is often a critical component in death investigation. Because commercially available immunoassays are often used in postmortem laboratories, it is important for those performing postmortem testing to be aware of the applicability of these new opiate cutoff concentrations on postmortem laboratories. Therefore, a study was performed to assess this applicability with 81 cases where the medical examiner ruled that the cause of death was narcotic intoxication.

Cases were selected from those investigated by the Office of the Chief Medical Examiner, State of Maryland or from those cases received by the Division of Forensic Toxicology, Armed Forces Institute of Pathology. All cases were signed out by the medical examiner as narcotic intoxication or intravenous narcotism. In each case, the blood free morphine concentration as measured by Diagnostic Products Corporation Coat-a-Count radioimmunoassay or gas chromatography–mass spectrometry (GC–MS) was greater than 25 ng/mL. Total morphine was quantitated in urine specimens by GC–MS as the butyl derivative; 6-AM was quantitated as either a trifluoroacetyl or pentafluoropropionic derivatives.

Table I summarizes the results from this study. All of the cases included in this study were deaths due to narcotic abuse. According to the old DOD and HHS guidelines of 300-ng/mL confirmation cutoff concentration, 23% of these cases (19 of 81) would have been called “negative for opiates,” despite the fact that 5 of the 10 specimens tested for 6-AM were positive at the 10-ng/mL cutoff. Using the current HHS confirmation cutoff concentration of 2000 ng/mL, 36% (29 of 81) would be called “negative for opiates,” despite the fact that 10 of the 15 specimens tested for 6-AM were positive at the 10-ng/mL cutoff.

Thirty-seven of the 52 specimens with urine morphine concentrations above 2000 ng/mL were tested for 6-AM at a cutoff concentration of 10 ng/mL. Thirty-six of these specimens had 6-AM concentrations greater than 10 ng/mL. The one specimen with a concentration less than 10 ng/mL was associated with a urine total morphine concentration greater than 4000 ng/mL; nevertheless, according to the 6-AM requirement, this specimen would have been called negative for opiates under the HHS guidelines.

Using the current DOD cutoff, 49% (40 of 81) of the cases would be called negative for morphine. This includes 18 of 23 “negative” specimens tested for 6-AM that were positive.

The purpose of this study was twofold: (1) to challenge the cutoff concentrations for opiates that were selected by HHS or DOD because the purpose of workplace drug testing is to deter the illegal use of opiates and these cutoffs are set well above the limit necessary to detect illegal use and (2) to caution those laboratories that perform postmortem and human performance toxicology testing with the goal of identifying all cases of opiate death or impairment that these cutoff concentrations are not appropriate in these laboratories.

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