Paradoxical results in urine drug testing for 6-acetylmorphine and total opiates: implications for best analytical strategy

A major task in urine drug testing is to detect heroin intake. The most common way of doing this is by using morphine as the analytical target in opiate immunoassay screening. However, this strategy sometimes leads to false-positive results because morphine is not a metabolite unique to heroin. The objective of this study was to evaluate the usefulness of the unique heroin metabolite 6-acetylmorphine (6-AM) as the primary analytical target in combination with morphine in the screening assay. A total number of 3521 randomly collected urine samples from 707 patients undergoing heroin substitution treatment were investigated for 6-AM and opiates by CEDIA (cloned enzyme donor immunoassay) and for opiates by DRI immunoassays and by gas chromatography-mass spectrometry (free 6-AM, free morphine, total morphine, and total codeine). The rate of positive outcome in the screening for 6-AM was 9.1% (cutoff 10 microg/L), and for opiates, it was 22.6% (cutoff 300 microg/L), which is in accordance with a known shorter detection time for 6-AM following heroin intake. However, by comparing 6-AM and opiate screening results at different cutoff levels, it was observed that 7-8% of the samples and 12.5% of the patients with detectable 6-AM had an unexpected low content of free and total morphine in the urine. This study confirms earlier observations that certain individuals may escape detection in urine drug testing when morphine is being utilized for the detection of heroin intake. The underlying mechanism for this may be a metabolic defect and/or interaction. It is concluded that 6-AM is a valuable target analyte in the screening of drugs of abuse in urine and may be used in combination with opiate screening in clinical testing.     

Adjunctive drug use among opiate addicts

In a study of 249 opiate (mainly heroin) addicts special attention was paid to adjunctive drug use. Generally, nicotine (cigarette smoking), alcohol and cannabis preceded the use of heroin, and continued to be used as adjunctive drugs after the establishment of heroin addiction. Nicotine was the most common substance used together with opiates. Alcohol and cannabis were used as adjunctive drugs in about two-thirds of the cases. In the late stages of heroin addiction, benzodiazepines were also used concomitantly with opiates. The most frequently reported reason for the use of adjunctive drugs was to intensify the effect of the opiate. Three-quarters or more of the addicts had used different adjunctive drugs to boost the euphoric feeling derived from the primary drug, i.e. heroin. Attempt at self-treatment of withdrawal symptoms was a less frequently reported reason for adjunctive drug use. The findings show that heroin addiction is the major problem. The use of adjunctive drugs, especially benzodiazepines, can be partly explained on economic grounds. They must be clearly distinguished from the primary drug of abuse, heroin. For policy-making decisions, it is important that the elimination of heroin abuse through effective prevention measures would ultimately wipe out the problem of adjunctive drug use, while reduction of the overall supply of heroin without reduction in actual demand might result in an increasing trend to adjunctive drug use.     

Detection of opiate use in a methadone maintenance treatment population with the CEDIA 6-acetylmorphine and CEDIA DAU opiate assays

Heroin, with a plasma half-life of approximately 5 min, is rapidly metabolized to 6-acetylmorphine (6-AM). 6-AM, a specific marker for heroin use, which also has a short half-life of only 0.6 h, is detected in urine for only a few hours after heroin exposure. Ingestion of poppy seeds and/or licit opiate analgesics can produce positive urine opiate tests. This has complicated the interpretation of positive opiate results and contributed to the decision to raise opiate cutoff concentrations and to require 6-AM confirmation in federally mandated workplace drug-testing programs. Microgenics Corp. has developed the CEDIA 6-AM assay, a homogeneous enzyme immunoassay for semiquantitative determination of 6-AM in human urine, in addition to its CEDIA DAU opiate assay. Urine specimens were collected 3 times per week from 27 participants enrolled in a clinical research trial evaluating a contingency management treatment program for heroin and cocaine abuse. Of the 1377 urine specimens screened, 261 (18.9%) were positive for opiates at > or = 300 ng/mL, 153 (11.1%) were positive for opiates at > or = 2000 ng/mL, and 55 (4.0%) were positive for 6-AM at > or = 10 ng/mL. For opiate-positive screens > or = 300 and > or = 2000 ng/mL, 91.3% and 80.8% confirmed positive for morphine or codeine at the respective gas chromatography-mass spectrometry (GC-MS) cutoffs. All specimens screening positive for 6-AM also confirmed positive by GC-MS at > or = 10 ng/mL. Increasing the opiate screening and confirmation cutoffs for the federal workplace drug-testing program resulted in 8% fewer opiate-positive tests; however, recent heroin use was not affected by this change.     

Benzodiazepine co-dependence exacerbates the opiate withdrawal syndrome

Patients seeking treatment for opiate withdrawal are commonly also dependent on benzodiazepines, although the interactions between benzodiazepine and opiate dependence and withdrawal syndromes have been subject to little systematic investigation. This is the first study comparing type, severity and course of opiate withdrawal symptoms between opiate dependent patients with, and without, concurrent benzodiazepine dependence. Patients dependent only on opiates (n = 39), and patients dependent on both opiates and benzodiazepines (n = 22), were recruited from consecutive admissions to an in-patient drug treatment unit. Quantity and duration of prior opiate use was similar for both groups. Patients completed daily self-ratings of opiate withdrawal (SOWS) for the duration of a standard in-patient detoxification treatment. Co-dependent patients were detoxified from benzodiazepines and opiates concurrently. Co-dependent patients reported a more severe withdrawal symptoms than patients withdrawing from opiates alone. Co-dependent patients had significantly more severe opiate withdrawal symptoms. Concurrent benzodiazepine withdrawal exacerbates opiate specific withdrawal symptoms. Possible psychological and neurophysiological mechanisms for the observed sensitisation are discussed.     

Monitoring opiate use in substance abuse treatment patients with sweat and urine drug testing

Although urine testing remains the standard for drug use monitoring, sweat testing for drugs of abuse is increasing, especially in criminal justice programs. One reason for this increase is sweat testing may widen the detection window compared to urine testing. Drug metabolites are rapidly excreted in urine limiting the window of detection of a single use to a few days. In contrast, sweat collection devices can be worn for longer periods of time. This study was designed to compare the efficacy of sweat testing versus urine testing for detecting drug use. Paired sweat patches that were applied and removed weekly on Tuesdays were compared to 3-5 consecutive urine specimens collected Mondays, Wednesdays, and Fridays (355 matched sweat and urine specimen sets) from 44 patients in a methadone-maintenance outpatient treatment program. All patches (N = 925) were extracted in 2.5 mL of solvent and analyzed by ELISA immunoassay for opiates (cutoff concentration 10 ng/mL). A subset (N = 389) of patches was analyzed by gas chromatography-mass spectrometry (GC-MS). Urine specimens (N = 1886) were subjected to qualitative analysis by EMIT (cutoff 300 ng/mL). Results were evaluated to (1) determine the identity and relative amounts of opiates in sweat; (2) assess replicability in duplicate patches; (3) compare ELISA and GC-MS results for opiates in sweat; and (4) compare the detection of opiate use by sweat and urine testing. Opiates were detected in 38.5% of the sweat patches with the ELISA screen. GC-MS analysis confirmed 83.4% of the screen-positive sweat patches for heroin, 6-acetylmorphine, morphine, and/or codeine (cutoff concentration 5 ng/mL) and 90.2% of the screen-negative patches. The sensitivity, specificity, and efficiency of ELISA opiate results as compared to GC-MS results in sweat were 96.7%, 72.2%, and 89.5%, respectively. Heroin and/or 6-acetylmorphine were detected in 78.1% of the GC-MS-positive sweat patches. Median concentrations of heroin, 6-acetylmorphine, morphine, and codeine in the positive sweat samples were 10.5, 13.6, 15.9, and 13.0 ng/mL, respectively. Agreement in paired sweat patch test results was 90.6% by ELISA analysis. For the purposes of this comparison of ELISA sweat patch to EMIT urine screening for opiates, the more commonly used urine test was considered to be the reference method. The sensitivity, specificity, and efficiency of sweat patch results to urine results for opiates were 68.6%, 86.1%, and 78.6%, respectively. There were 13.5% false-negative and 7.9% false-positive sweat results as compared to urine tests. Analysis of sweat patches provides an alternate method for objectively monitoring drug use and provides an advantage over urine drug testing by extending drug detection times to one week or longer. In addition, identification of heroin and/or 6-acetylmorphine in sweat patches confirmed the use of heroin in 78.1% of the positive cases and differentiated illicit heroin use from possible ingestion of codeine or opiate-containing foods. However, the percentage of false-negative results, at least in this treatment population, indicates that weekly sweat testing may be less sensitive than thrice weekly urine testing in detecting opiate use.     

Opiate dependence--the role of benzodiazepines

In a recent epidemiological study of 249 opiate addicts in the State of Penang, Malaysia, the use of benzodiazepines, its temporal relationship to opiate addiction and the reasons for use of benzodiazepines were examined. Just over a half of the opiate addicts indicated use of benzodiazepines in their lifetime. Use of 7 different benzodiazepines was reported, among them flunitrazepam most frequently. A substantial proportion had discontinued the use of benzodiazepines after initial experimentation. Just over a quarter had used them in the last 24 hours. Benzodiazepine use starts on average 3 to 6 years later than heroin use. The most common reason cited for benzodiazepine use was to enhance the feeling of 'high' from the opiates. These findings can be explained, at least partly, by economic factors. Reasons that could be qualified as attempts to autotherapy did not exceed 20%. None of the opiate addicts had reported isolated benzodiazepine use for fun and pleasure. From the time course of use as well as from the reasons given by the addicts, it is evident that benzodiazepines are not primary drugs of abuse. Comparing their figures from Malaysia with figures from Germany and England the authors cannot explain the preferred use of flunitrazepam by Malaysian addicts by the existence of special properties of this substance.     

Street fentanyl use: Experiences,preferences, and concordance between self-reports and urine toxicology

BackgroundConducted in Dayton, Ohio, the study aims to characterize user knowledge and experiences with non-pharmaceutical fentanyl-type drugs (NPFs) and compare self-reports with urine toxicology for NPFs and heroin.MethodsBetween May 2017–January 2018, 60 individuals who self-reported heroin/NPF use were interviewed using structured questionnaire on socio-demographics, NPF and other drug use practices. Unobserved urine samples were collected and analyzed using: 1) liquid-chromatography-tandem mass spectrometry (LC–MS/MS)-based method (Toxicology lab) to identify 34 fentanyl analogues, metabolites, and other synthetic opioids; 2) immunoassay-based method to screen for opiates (heroin). Sensitivity, specificity and Cohen’s kappa were calculated to assess agreement between self-reports and urine toxicology.ResultsThe sample was 52% female, and over 90% white. Almost 60% reported preference for heroin, and 40% for NPF. Participants endorsed a number of ways of distinguishing heroin from NPF, including appearance (88.3%), effects (76.7%), taste (55%), and information provided by dealers (53.3%). Almost 80% felt confident they could distinguish heroin from NPF, but knowledge about fentanyl analogues was limited. LC–MS/MS testing identified 8 types of NPFs. Over 88% tested positive for NPFs, including 86% fentanyl, 48% carfentanil, 42% acetyl fentanyl. About 47% screened positive for opiates/heroin, and all of them were also positive for NPFs. When comparing self-reported use of NPF to urine toxicology, sensitivity and specificity were relatively high (84% and 83.3%, accordingly), while Cohen’s Kappa was 0.445, indicating fair agreement. Sensitivity and specificity were lower for heroin (77.8% and 50.0%, accordingly), and Cohen’s Kappa was 0.296, indicating low agreement between self-reports of heroin use and urine toxicology.DiscussionNearly 90% of the study participants tested positive for NPF-type drugs. Participants were more likely to over-report heroin use and underreport NPF use. The majority had little knowledge about fentanyl analogues. Study findings will inform development of novel harm reduction approaches to reduce overdose mortality.     

Utility of sweat patch testing for drug use monitoring in outpatient treatment for opiate dependence

We evaluated the utility of sweat testing for monitoring of drug use in outpatient clinical settings and compared sweat toxicology with urine toxicology and self-reported drug use during a randomized clinical trial of the efficacy of buprenorphine for treatment of opioid dependence in primary care settings. All study participants (N = 63) were opiate-dependent, treatment-seeking volunteers. The results based on toxicology tests obtained from 188 properly worn and unadulterated patches (out of 536 applied) show that the level of agreement between positive sweat test results and positive urine results was 33% for opiates and 92% for cocaine. The findings of this study, that there is a low acceptability of sweat patch testing by patients (only 54.3% were brought back attached to the skin) and that weekly sweat testing is less sensitive than weekly urine testing in detecting opiate use, suggest limited utility of sweat patch testing in outpatient clinical settings.     

An evaluation of the OnTrak Testcup-er on-site urine drug-testing device for drugs commonly encountered from emergency departments

We evaluated the performance of the Roche OnTrak Testcup-er (TC-er), an on-site drug-testing device, for the detection of amphetamines (AMP), barbiturates (BRB), benzodiazepines (BNZ), benzoylecgonine (BE), and opiates (OPI) in urine specimens from hospital emergency departments. This device utilizes a competitive binding microparticle immunoassay to simultaneously determine the presence of the following drugs or drug classes in urine at and above the following cut-off concentrations: AMP, 1000 ng/mL; BRB, 200 ng/mL; BNZ 200 ng/mL; BE, 300 ng/mL; and OPI, 300 ng/mL. One hundred forty-nine urine specimens received from emergency departments were simultaneously tested by the EMIT II monoclonal immunoassay (Emit) and TC-er. Specimens yielding discordant results were analyzed by gas chromatography-mass spectrometry. There was a 98% (146/149) agreement of results between the methods for the presence or absence of drugs. TC-er yielded 110 positive drug findings in 79 specimens, and Emit yielded 102 positive drug findings in 76 specimens. There was a 97% agreement between the methods for positive findings of at least one drug. The majority of discordant results were due to variations in selectivity of the assays for phenobarbital and BNZ metabolites. TC-er yielded a single false-positive result for amphetamines, and barbiturates, possibly three false-positive benzodiazepine results, and a single false-negative opiate finding. This represented four certain errors out of 745 total results, or a 0.4% error rate. If the three false-positive BNZ results were also considered, the error rate would be 0.9%. TC-er demonstrated acceptable linearity around the cut-off concentration of each drug. The TC-er was determined to be a reliable device for rapid on-site testing of emergency department urine specimens.     

False-Positive Buprenorphine EIA Urine Toxicology Results Due To High Dose Morphine: A Case Report

In monitoring a patient with chronic pain who was taking high-dose morphine and oxycodone with weekly urine enzymatic immunoassay (EIA) toxicology testing, the authors noted consistent positives for buprenorphine. The patient was not taking buprenorphine, and gas chromatography/mass spectroscopy (GCMS) testing on multiple samples revealed no buprenorphine, indicating a case of false-positive buprenorphine EIAs in a high-dose opiate case. The authors discontinued oxycodone for a period of time and then discontinued morphine. Urine monitoring with EIAs and GCMS revealed false-positive buprenorphine EIAs, which remained only when the patient was taking morphine. When taking only oxycodone and no morphine, urine samples became buprenorphine negative. When morphine was reintroduced, false-positive buprenorphine results resumed. Medical practitioners should be aware that high-dose morphine (with morphine urine levels turning positive within the15,000 to 28,000 mg/mL range) may produce false-positive buprenorphine EIAs with standard urine EIA toxicology testing.     

Multiple drug use: patterns and practices of heroin and crack use in a population of opiate addicts in treatment

One hundred and sixteen opiate addicts attending treatment services in south London were interviewed about their drug use patterns. In the month before interview, 90% reported heroin use, while 60% had used crack cocaine and 58% alcohol. In the same period, 70% of participants reported multiple drug use, particularly concurrent heroin and crack cocaine use. Of the patients who reported using other drugs with heroin, two-third used crack cocaine, 11% diazepam, 9% methadone and 8% cocaine powder. Twenty-six per cent of crack users sample had injected crack cocaine, which provides confirmation of the increasing prevalence of this recent trend in studies using similar samples. Male participants were significantly more likely to use benzodiazepines with heroin, while women were more likely to use crack alongside heroin (and used larger quantities). These findings have implications for the treatment and management of multiple drug users, for whom opiates may be only a part of their drug-using repertoire.     

Variables associated with perceived sleep disorders in methadone maintenance treatment (MMT) patients

To characterize sleep disorders in methadone maintenance treatment (MMT) patients, we evaluated sleep quality of 101 non-selective patients from our MMT clinic in Israel between July, 2003 and July, 2004 by using the self-report questionnaire Pittsburgh Sleep Quality Index (PSQI). Patients' urine tests were analyzed for methadone metabolite, opiates, benzodiazepine, cocaine, cannabis and amphetamines. Their urine results for drug abuse throughout the months prior to filling in the questionnaire and their maintenance methadone doses were recorded. Drug abuse was defined by at least one positive urine test. Methadone serum levels were available in 55 patients, assessed by Gas Chromatography Mass Spectroscopy. The patients' self-reported chronic pain questionnaires and their diagnosed psychiatric disorders were analyzed. Out of the 101 study patients, 78.2% were male, 52.5% had psychiatric disorders, 46.5% reported having chronic pain and 46.5% had positive urine for benzodiazepine. The mean daily methadone dose was 157+/-52.9 mg. The mean PSQI score was 9+/-4.8 (75.2% had scores >5 indicating "poor sleepers"). PSQI scores were higher in patients with positive urine for benzodiazepine, chronic pain and psychiatric disorders and they correlated with years of opiate abuse before admission to MMT, and with the methadone dose (r=0.48, p<0.0005). The latter two also correlated with each other. The PSQI was not correlated with duration in MMT, gender, age, abuse of opiates, cannabis or cocaine. We concluded that sleep disorders should be evaluated and treated among MMT patients, particularly in those with psychiatric disorders, benzodiazepine abuse, chronic pain and high methadone dose.     

Evaluation of the Cedia heroin metabolite (6-AM) immunoassay with urine specimens from A criminal justice drug-testing program

The ability to differentiate illicit from legitimate drug use in a drug-testing program would decrease costs by reducing the number of screening specimens requiring confirmation and also reduce the stigma attached to positive preliminary test results. Because many screening tests for drug detection use immunoassays, increasing the specificity of these tests has been a goal of manufacturers. In this study we evaluated the utility of one such assay, the Cedia heroin metabolite (6-acetylmorphine, 6-AM) assay to reliably detect heroin use. Specimens (N = 525) from a criminal justice drug-testing program were screened with this assay (cutoff concentration = 10 ng/mL 6-AM) and any positive samples were confirmed by gas chromatographic-mass spectrometric analysis (lower reporting limit for 6-AM = 5 ng/mL). The confirmation rate for the enzyme immunoassay (EIA) was 98% (517/525). Specimens contained 6-AM at concentrations ranging from 5 to 16,923 ng/mL (mean = 1251; median = 317). All confirmed specimens also contained morphine (range: 8-222,427 ng/mL; mean = 11,203 ; median = 4134). When challenged with standard drug solutions, the EIA correctly identified drug-free urine and produced positive results (lowest concentration, in ng/mL, that produced a positive result) with morphine at 10,000; oxycodone at 61,000; codeine at 60,000; hydromorphone at 10,000; hydrocodone at 60,000, 6-AM at 10, and pentazocine at 35,000 ng/mL. The Cedia heroin metabolite (6-AM) assay produced a high confirmation rate when challenged with urine specimens and therefore should be a useful tool in forensic toxicology. Potential users should be aware that high concentrations of other opioids (e.g., morphine, oxycodone) and structurally related compounds (e.g., pentazocine) may produce positive results.     

Sequence of onset of different drug use among opiate addicts

The temporal sequence of drug use should reveal which drugs are precursors to heroin and which drugs are used subsequent to the establishment of heroin addiction as adjunctive drugs. This temporal sequence was examined in an epidemiological study. Out of 249 opiate addicts interviewed in the area of Penang, Malaysia, this sequence of drugs could be obtained in 248 cases. The mean (median) age for first use of nicotine is 15.5 (15) years, alcohol 18.4 (18) years, cannabis 17.8 (17) years, heroin 21.8 (21) years, opium 22.8 (22) years, and benzodiazepines 25.8 (25) years. The age of first use of different drug types is presented in some detail. The patterns of sequence of drug use was analyzed for the five major and most frequently reported drugs, i.e. alcohol, cannabis, heroin, opium and benzodiazepines. Nicotine, used as first drug in almost all cases, was omitted in this analysis. A clear trend to multiple drug abuse emerges from this analysis; the biggest number of cases were users of 4 drugs (81 cases), followed by 3 drugs (59 cases) and 5 drugs (58 cases). Thus, nicotine, alcohol and cannabis are precursors of heroin addiction. Other adjunctive drugs become important only after heroin addiction. Among these substances, opium and benzodiazepines are numerically preponderant.     

Gatifloxacin interference with opiate urine drug screen

A 48-year-old man participating in a residential treatment program was treated with gatifloxacin for a urinary tract infection. While taking the antibiotic, two urine screens were positive for opiates; results of previous urine opiate screens had been negative. Confirmatory tests using a different assay method, however, gave negative results for opiates. Two weeks after completing gatifloxacin therapy, the patient's urine screen was negative for opiates. Application of the Naranjo adverse drug reaction probability scale indicated that gatifloxacin probably was associated with this patient's positive urine opiate screen. Fluoroquinolones as a class are among several compounds that have demonstrated a propensity to cross-react with enzyme immunoassay urine drug screens for opiates. Occurrence of cross-reactivity appears to vary among individual assays. The mechanism by which fluoroquinolones cross-react with the immunoassay is unknown. Falsepositive results could have negative effects on patient care, and ramifications of a positive drug screen include possible dismissal from a substance abuse treatment program. Confirmatory analysis using a different assay method is therefore necessary to verify the presence of the target drug.     

Excretion profile of opiates in dependent patients in relation to route of administration and type of drug measured in urine with immunoassay

It is accepted that opiates are detectable in urine within three days from the last dose at a cut-off value of 300 ng/mL. In our clinical practice, some patients tested positive for morphine even after a week of detoxification. The present study evaluates the time course of opiate excretion in urine of dependent subjects (F11.25 according to ICD-10) in relation to route of administration and a kind of street heroin. The group comprised 71 men treated for opiate dependency: 33 of them used heroin exclusively by inhalation; 26 i.v.; 12 used i.v. homemade poppy straw decoctions. Opiate levels were measured once a day by fluorescence polarization immunoassay (TDx Abbott). Detection time ranged from 3 to 10 days for cut-off value 300 ng/mL and from less than one up to seven days for cut-off value 2000 ng/mL. The increases in urine drug concentration that result from changes in urinary output may be mistakenly interpreted as a new drug use. Normalization of drug excretion to urine creatinine concentration reduces the variability of drug measurement attributable to urine dilution. The time function of creatinine normalized opiate concentration has a log-linear character, and decreases at a rate of 2.5 per day on average. New "normalized" cut-off values were proposed: 225 ng/mg creatinine, 1500 ng/mg creatinine, and 3750 ng/mg creatinine that corresponds to 300 ng/mL urine, 2000 ng/mL urine, and 5000 ng/mL urine.     

Comparison of the Microgenics CEDIA heroin metabolite (6-AM) and the Roche Abuscreen ONLINE opiate immunoassays for the detection of heroin use in forensic urine samples

Current Department of Defense (DoD) and Department of Health and Human Services (HHS) procedures for the detection of heroin abuse by testing urine utilize an initial opiate (codeine/morphine) immunoassay (IA) screen followed by gas chromatography-mass spectrometry (GC-MS) confirmation of 6-acetylmorphine (6-AM), if the morphine concentration is above established cutoff. An alternative to the current opiates screen for heroin abuse is the direct IA for the metabolite of heroin, 6-acetylmorphine. In this regard, the performance of the Microgenics CEDIA heroin metabolite (6-AM) screening reagent was assessed. This evaluation was conducted on the P module of a Hitachi Modular automated IA analyzer calibrated using 6-AM at 10 ng/mL. Reproducibility, linearity, accuracy, sensitivity, and interferences associated with use of the 6-AM IA reagent were evaluated. The IA reagent precision (percent coefficient of variation (%CV)) around each of seven standards was less than 0.63%, with a linearity (r(2)) value of 0.9951. A total of 37,713 active duty service members' urine samples were analyzed simultaneously using the CEDIA heroin metabolite (6-AM) reagent and the Roche Abuscreen ONLINE opiate reagent to evaluate both the prevalence rate of 6-AM in the demographic group and the sensitivity and specificity of the reagents for the detection of heroin use. Of the 37,713 samples tested using the CEDIA heroin metabolite (6-AM) reagent, three samples screened positive at the DoD and HHS cutoff of 10 ng/mL. One of the three samples confirmed positive for 6-AM by GC-MS above the cutoff of 10 ng/mL, the two remaining samples confirmed negative for 6-AM at a GC-MS limit of detection (LOD) of 2.1 ng/mL. In contrast, the Roche Abuscreen ONLINE opiate IA produced 74 opiate-positive results for codeine/morphine, with 6 of the 74 specimens confirming positive for morphine above the DoD cutoff concentration of 4000 ng/mL (8% DoD morphine confirmation rate), only one of the 74 opiate-positive screen specimens confirmed positive for 6-AM above the 10 ng/mL GC-MS cutoff concentration. As a further check of the sensitivity and specificity of the Microgenics 6-AM IA reagent, human urine samples (n = 87) known to contain 6-AM by GC-MS, were re-analyzed using both IA reagents. All 87 of the samples screened positive using the CEDIA heroin metabolite (6-AM) assay. However, using the Roche ONLINE opiate reagent, 12 of the known 6-AM positives screened negative at the DoD and HHS screening cutoff of 2000 ng/mL (morphine). Of the remaining 75 samples that screened positive by the ONLINE opiate reagent, five of the samples did not contain morphine above the DoD GC-MS cutoff concentration of 4000 ng/mL and would not have required 6-AM analysis. However, under the HHS GC-MS morphine cutoff concentration of 2000 ng/mL all 75 samples would have required 6-AM analysis. Furthermore, using the current DoD opiate screen, 17 out of 87 samples known to contain 6-AM would have gone undetected (19.5% false-negative rate); additionally, even under the more stringent HHS opiate screening standards 12 out of the 87 samples known to contain 6-AM would also have gone undetected (13.8% false-negative rate). The Microgenics CEDIA heroin metabolite (6-AM) reagent assay appears well adapted for the rapid and specific detection of heroin abuse as an alternative for, or an adjunct test to, the current opiates (codeine/morphine) IA screening procedure.