Clinical Chemistry
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Clinical Chemistry 48: 203-204, 2002;
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(Clinical Chemistry. 2002;48:203-204.)
© 2002 American Association for Clinical Chemistry, Inc.


Letters

Rifampin Interference with Opiate Immunoassays

Rose Daher1a, Joud H. Haidar1 and Hadi Al-Amin1

1 Department of Pathology, and Laboratory Medicine, American University of Beirut Medical Center, Beirut, Lebanon

aAddress correspondence to this author at: Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, PO 11-0236, Beirut, Lebanon. Fax 961-1-370845; e-mail rd02{at}aub.edu.lb.


To the Editor:

Clinical toxicology in emergency situations necessitates the availability of rapid analytical tests for different substances in a variety of settings. The primary question asked by clinicians is what compounds may have been ingested. In cases of suspected drug abuse or overdose, rapid screening by immunoassays has made this possible. However, many limitations are inherent in these methods, which necessitate confirmation by an alternative method such as gas chromatography-mass spectrometry (1). Here we present a case of drug interference with certain screening methods for opiates in urine.

A 7-year-old male (Table 1 , patient 1) presented to the emergency unit at the American University of Beirut Medical Center with a progressive decrease in his level of consciousness over the previous 3 weeks. He was transferred from another hospital because of a suspicion of tuberculous meningitis. As part of the workup for this case, a urine drugs of abuse screen was ordered, which was positive for opiates by the Syva RapidTest (Dade Behring) on two occasions after being negative at the time of admission (Table 1 ). However, the patient was never on any opiates or opiate-like medication. After a review of the patient’s chart, the interfering substance in this positive opiate screen was suspected to be rifampin (rifampicin) (2). Confirmation of opiates in a urine sample collected on day 4 after admission by gas chromatography-mass spectrometry was negative. The actual opiates targeted by this analysis were pholcodine, codethyline, codeine, morphine, and monoacetylmorphine.


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Table 1. Opiate results for different screening methods and for gas chromatography-mass spectrometry.

To further characterize this interference, two patients taking rifampin at our institution were followed up. Patient 2 was on rifampin for brucellosis and patient 3 for pulmonary tuberculosis (Table 1Up ). Urine samples from both patients were collected before initiation of therapy and 1 h after a 600-mg rifampin dose. Patients consented to urine drugs of abuse screens before samples were collected. The original screen was performed using the Syva RapidTest for drugs of abuse. In parallel, we also tested the Triage (Biosite Diagnostics) and Genix RapidTech (Genix Technology) immunoassays (Table 1Up ). Pre-rifampin samples were negative for opiates by the three methods, but 1-h post-rifampin samples were positive for opiates by the Syva and Genix reagents and negative by the Triage. These positive samples were negative when analyzed by gas chromatography-mass spectrometry. To investigate the concentration at which rifampin interferes with the Syva and Genix opiate methods, we added different rifampin concentrations to a previously tested blank urine sample. At 300 mg/L, rifampin started to interfere with the Syva reagents. For the Genix reagents, the interference occurred at a much lower concentration (0.05 mg/L). The Triage is a competitive binding immunoassay, whereas the Syva and Genix assays are one-step immunochromatographic assays for rapid detection of opiates in urine with a cutoff concentration of 300 mg/L. Information about rifampin cross-reactivity with these immunoassays was not available from the manufacturers. The only reported interference for rifampin is with the opiates kinetic interaction of microparticles in solution (KIMS) method for Roche reagents on Cobas Integra (3)(4).

The antibiotic rifampin is usually part of the treatment of tuberculosis, especially in patients with concomitant human immunodeficiency virus infection. Generally, drug abuse in some of these patients necessitates screening for opiates (4). In addition, in cases of mental confusion associated with tuberculous meningitis or rifampin toxicity, it is not uncommon for a drugs of abuse screen to be ordered. Depending on the specificity of the method, rifampin interference could be the cause of false-positive opiate screening results. Therefore, the presence of rifampin treatment mandates confirmatory testing for opiates because it can interfere with the predictive value of certain rapid screening assays (5).

We recommend that each laboratory evaluates rifampin interference with the opiates immunoassay in use. In addition, each laboratory should maintain an updated listing of reported interference problems with immunoassays, as part of a quality assurance program, and disseminate this information to the medical community (6). However, this rapid screen serves the need for emergency drug testing, but it must always be complemented by confirmation.


Acknowledgments

We would like to acknowledge the support of Elie Salameh and Pasteur Cerba Laboratories (95066 Cergy Pontoise, Cedex 9, France) for performing the gas chromatography-mass spectrometry analysis of opiates in this study as a gift.


References

  1. Warner A, Hassan FM, Fant WK. Drug abuse testing: pharmacokinetic and technical aspects. Ther Drug Monit 1986;8:1-11.[Medline] [Order article via Infotrieve]
  2. Leikin JB, Paloucek FP. Poisoning and toxicology handbook, 2nd ed 1996:683 Lexi-Comp Inc Cleveland. .
  3. Van As H, Stolk LML. Rifampicin cross-reacts with opiate immunoassay. J Anal Toxicol 1999;23:71.[Medline] [Order article via Infotrieve]
  4. De Paula M, Saiz LC, Gonzalez-Revalderia J, Pascual T, Alberola C, Miravalles E. Rifampicin causes false-positive immunoassay results for urine opiates. Clin Chem Lab Med 1998;36:241-243.[Web of Science][Medline] [Order article via Infotrieve]
  5. Spiehler V. Sensitivity, specificity, and predictive value in quality assurance. Welch SL eds. QA issues in clinical toxicology 1996:1-4 AACC Press Washington. .
  6. Annesley TM. Quality assurance and quality control in clinical toxicology. Welch SL eds. QA issues in clinical toxicology 1996:31-56 AACC Press Washington. .



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