Sensitivity of an opiate immunoassay for detecting hydrocodone and hydromorphone in urine from a clinical population: analysis of subthreshold results.

Urine drug testing (UDT) is an emerging standard of care in the evaluation and treatment of chronic non-cancer pain patients with opioid analgesics. UDT may be used both to verify adherence with the opioid analgesic regimen and to monitor abstinence from non-prescribed or illicit controlled substances. In the former scenario, it is vital to determine whether the drug is present in the urine, even at low concentrations, because failure to detect the drug may lead to accusations of opioid abuse or diversion. Opiate immunoassays typically are developed to detect morphine and are most sensitive to morphine and codeine. Although many opiate immunoassays also detect hydrocodone (HC) and/or hydromorphone (HM), sensitivities for these analytes are often much lower, increasing the possibility of negative screening results when the drug is present in the urine. We selected 112 urine specimens from patients who had been prescribed HC or hydromorphone but were presumptive negative by the Roche Online DAT Opiate II™ urine drug screening assay, which is calibrated to 300 ng/mL morphine. Using a GC/MS confirmatory method with a detection limit of 50 ng/mL both for HC and for HM, one or both of these opiates were detected in 81 (72.3%) of the urine specimens. Examination of the raw data from these presumptive negative opiate screens revealed that, in many cases, the turbidity signal was greater than the signal obtained for the negative control, but less than the signal for the 300 ng/mL (morphine) threshold calibrator. A receiver operating characteristic curve generated for the reciprocal of the ratio of turbidity measurements in the patient specimens and negative (drug-free) controls, against the presence or absence of HC and/or HM by confirmatory analyses, produced an area under the curve of 0.910. We conclude that this opiate immunoassay has sufficient sensitivity to detect HC and/or HM in some urine specimens that screen presumptive negative for these commonly prescribed opiates at the established threshold.

Failure of amoxicillin to produce false-positive urine screens for cocaine metabolite.

Amoxicillin has been causally linked in the lay and medical literature to false-positive urine drug screens for cocaine metabolites. An exhaustive search of the peer-reviewed medical literature revealed no data to support this link. We hypothesized that amoxicillin does not cause false-positive urine drug screens for cocaine metabolites. To test this hypothesis, we examined the urine of 33 subjects administered a course of amoxicillin, subjecting the specimens to four common urine screening immunoassays. Thirty-one specimens were negative for the cocaine metabolite, benzoylecgonine (BE), by all four screening methods; two were positive for BE by all four screening methods. Both positive specimens were confirmed by gas chromatography-mass spectrometry (GC-MS) for the presence of BE at > 150 ng/mL. Three specimens that screened negative, but produced absorbance values that were intermediate between negative and positive controls, were submitted for GC-MS analysis; BE was detected in all three specimens at concentrations of 54, 94, and 119 ng/mL. Twenty-eight specimens produced screening results indistinguishable from negative controls. Within the limitations of the study design, we conclude that amoxicillin is unlikely to produce false-positive urine screens for cocaine metabolites.

False-positive acetaminophen results in a hyperbilirubinemic patient.

BACKGROUND: Acetaminophen was falsely detected in the plasma of a severely jaundiced patient, and a methodologic interference from bilirubin was suspected. METHODS: Acetaminophen was measured by an enzymatic method (GDS Diagnostics). The putative bilirubin interference was investigated in 12 hyperbilirubinemic specimens and in bilirubin linearity calibrators. The analytical method was modified to correct for background absorbance at a second wavelength. Hyperbilirubinemic specimens were fortified with acetaminophen to assess the effect of the interference on acetaminophen measurements. RESULTS: Acetaminophen was detected in 12 specimens from hyperbilirubinemic patients without a history of recent acetaminophen exposure. Dilution of hyperbilirubinemic specimens produced a nonproportional decrease in apparent acetaminophen concentrations, and no acetaminophen was detected when bilirubin was <50 mg/L. Background correction at a second wavelength failed to compensate for the interference. Although erroneous acetaminophen concentrations were detected in all specimens with high bilirubin, acetaminophen measurements in fortified specimens were accurate. CONCLUSION: The data are consistent with bilirubin interference in the enzymatic and/or chromogenic reactions involved in the acetaminophen method.