Kavain Interference with Amphetamine Immunoassay

Author(s):  
H Madhavaram ◽  
T Patel ◽  
C Kyle

Abstract We encountered unexpected false-positive urine results in three patients for amphetamine-type substances by immunoassay (IA), measured as part of community drug prevention programs. Kavain was identified in all three urine samples by gas chromatography-mass spectrometry (GC-MS). No other potential cross-reactants were found. Kavain is a kava-lactone present in kava, a ceremonial and recreational drink derived from the roots and stems of the plant Piper methysticum. It is consumed regularly by many indigenous Pacific and Australian Aboriginal communities. Urine IA was performed on a Beckman Coulter AU480 Analyzer using cloned enzyme donor immunoassay (CEDIA) amphetamine-type substance reagent and DRI ethanol reagent. We purchased three different kava powders from local kava clubs and dissolved in ethanol, then evaporated and reconstituted in blank urine and analyzed by IA, GC-MS for amphetamine-type substances. Additionally, authentic kavain standard was also tested for cross-reactivity by IA and analyzed by GC-MS to compare the mass fragmentation pattern and retention time with the kava powder and patient specimens. The patient urine samples tested positive by CEDIA IA for amphetamines. However, when analyzed by GC-MS, they were negative for amphetamine-type but contained kavain. The kava powders and kavain standard all cross-reacted with the amphetamine IA to give falsely detected results. GC-MS did not identify any amphetamine-type compounds in any of the kava powders nor in the kavain standard. To our knowledge, this is the first report of false-positive amphetamine measurements due to kavain, a component of the kava drink, widely consumed in Oceania and Australasia.

Author(s):  
Mohamed Saleem ◽  
Helen Martin ◽  
Anne Tolya ◽  
Penny Coates

Background Interference from opiates in the Microgenics CEDIA® Buprenorphine assay is known to produce false-positive buprenorphine screening immunoassay results necessitating confirmatory buprenorphine testing by chromatography/mass spectrometry methods. Method We reviewed data on falsely positive buprenorphine immunoassay screen (cut-off ≥ 5  µg/L) but negative for buprenorphine by gas chromatography mass spectrometry (cut-off ≥ 5  µg/L) and had a positive opiate immunoassay result (cut-off ≥ 300  µg/L). The results were collected over three months, and the data were evaluated to determine whether there is an opiate immunoassay screen concentration below which a false-positive buprenorphine result will not occur. Results We found that cross-reactivity in the CEDIA® buprenorphine immunoassay by opiates at concentrations <2000  µg/L will not cause a false-positive buprenorphine result. After changing our practice to not proceed with confirmatory buprenorphine gas chromatography mass spectrometry assay when the opiate screening concentration is below an even more conservative cut-off of <1500  µg/L, we estimate a potential cost-saving of AU$ 17,810 per year without compromising clinical care. Conclusion Samples with CEDIA® opiate immunoassay result <2000  µg/L and a positive CEDIA® buprenorphine immunoassay screen do not require confirmatory testing for buprenorphine.


Author(s):  
Sabine Plattner ◽  
Marion Pavlic ◽  
Florian Pitterl ◽  
Birthe Schubert

Abstract Buprenorphine is a semi-synthetic opioid which is often used in opiate maintenance therapy. For this purpose, regular toxicological analyses of urine samples are mandatory. For fast analytical results, analyses are commonly performed by immunoassay, e.g. Thermo Scientific™ CEDIA® Buprenorphine or Buprenorphine II assay. One drawback of immunoassay-based methods are possible cross-reactions with other substances. Several structural related and unrelated drugs have already been checked for cross-reactivity to CEDIA® Buprenorphine II immunoassay. In contrast, cross-reactivities have not been checked for any food additives. In the present study, a cross-reaction of CEDIA® Buprenorphine II assay to steviol glucuronide was investigated. Steviol glucuronide is a phase II metabolite of the sugar substitute Stevia. For our study, 32 urine samples of patients in rehabilitation centers were collected. These samples tested positive with the CEDIA® Buprenorphine II immunoassay. These findings were suspicious, since it was highly unlikely that the patients in those institutions had access to buprenorphine. The absence or presence of buprenorphine in urine samples was evaluated by a validated gas chromatography mass spectrometry method. In order to determine the concentration of steviol glucuronide in urine samples, a liquid chromatography-tandem mass spectrometry method has been developed and fully validated according to the respective guidelines of the German Society of the Toxicological and Forensic Chemistry. Cross-reactivity of steviol glucuronide in the CEDIA® Buprenorphine II immunoassay was observed at concentrations above 15000 µg/L. These findings demonstrate that food additives should also be considered as compounds that may reduce the selectivity of immunoassays. This places emphasis on the importance of confirming implausible results by selective analytical methods.


1997 ◽  
Vol 43 (4) ◽  
pp. 635-637 ◽  
Author(s):  
Detlef Ritter ◽  
Cherise M Cortese ◽  
Linda C Edwards ◽  
Judith L Barr ◽  
Hyung D Chung ◽  
...  

Abstract We found a high rate (4.2%) of positive results for lysergic acid diethylamide (LSD) by Emit in 1898 urine samples that were submitted primarily from psychiatric patients for drugs-of-abuse (DOA) testing. Specimens that tested positive for LSD by Emit subsequently tested negative for LSD with two RIAs. Furthermore, LSD was not detected in randomly selected Emit-positive urine samples by gas chromatography–mass spectrometry. Normal urine samples tested positive for LSD by Emit when they were supplemented with therapeutic medications that were prescribed for patients with positive urine LSD results by Emit. These therapeutic drugs interfered specifically with the Emit assay for LSD, since other Emit DOA tests were not affected by these medications at the tested concentrations.


1994 ◽  
Vol 40 (10) ◽  
pp. 1944-1949 ◽  
Author(s):  
S H Mishalani ◽  
J Seliktar ◽  
G D Braunstein

Abstract We evaluated the performance of four visually read pregnancy tests (TestPack Plus hCG Combo, ICON II hCG, SureCell hCG-Serum/Urine and PregnaGen 1-Step) designed to detect increased concentrations of choriogonadotropin (hCG) in either serum or urine samples. The biochemical sensitivities and specificity in both serum and urine samples were similar for each kit. All kits correctly identified pregnancy serum samples: The TestPack Plus hCG Combo and SureCell hCG-Serum/Urine were 100% specific; the other two kits exhibited a few false-positive results. For urine samples the ICON II hCG test was 100% sensitive, and the other three were 99.5% sensitive, with false-positive urine results occasionally reported by the PregnaGen 1-Step and ICON II hCG tests. Quantitative hCG concentrations could be estimated in pregnancy serum samples, but not urine samples, through determination of the time elapsed from the sample application or addition of the final reagent to the first appearance of a positive result.


2019 ◽  
Vol 44 (2) ◽  
pp. 200-205 ◽  
Author(s):  
Marion Leclercq ◽  
Marion Soichot ◽  
Brigitte Delhotal-Landes ◽  
Emmanuel Bourgogne ◽  
Hervé Gourlain ◽  
...  

Abstract Amphetamines, frequently used recreational drugs with high risk of toxicity, are commonly included in urine drug screens. This screening is based on enzyme immunoassay, which is a quick and easy-to-perform technique, but may lack specificity resulting from cross-reactivity with other compounds, causing false positive results. We present two cases of presumed false positive MULTIGENT® amphetamine/methamphetamine and MULTIGENT® ecstasy (Abbott®) immunoassays with the beta-blocker metoprolol. Both metoprolol-poisoned patients presented positive urine screening despite no history of drug abuse. No confirmation for amphetamine molecular structures was found with gas chromatography–mass spectrometry. The cross-reactivity was further investigated by doping urine samples with metoprolol and its two major phase-I metabolites. Metoprolol showed positive results for both amphetamine and MDMA tests at low concentrations (200 and 150 μg/mL, respectively). Metoprolol metabolites cross-reacted with the amphetamines immunoassay only, but at higher concentrations (i.e., 2000 μg/mL for α-hydroxymetoprolol and 750 μg/mL for O-demethylmetoprolol). In conclusion, false positive results in amphetamines and MDMA immunoassays are possible in the presence of metoprolol. Toxicologists should be aware of frequent analytical interferences with immunoassays and a detailed medication history should be taken into consideration for interpretation. In vitro investigation of suspected cross-reactivity should include not only the parent drug but also its related metabolites.


2001 ◽  
Vol 84 (4) ◽  
pp. 1025-1030 ◽  
Author(s):  
Simon A Haughey ◽  
G Andrew Baxter ◽  
Christopher T Elliott ◽  
Bjorn Persson ◽  
Carin Jonson ◽  
...  

Abstract Clenbuterol (CBL) is an orally active β2-adrenoceptor agonist which has been used in veterinary medicine as a broncodilator and an agent of uterine relaxation. It has however become better known as a drug used illegally to promote growth in farm animals. A rapid an sensitive biosensor assay was developed to detect CBL residues in bovine urine. The method involved a simple extraction procedure using tert-butyl methyl ether followed by analysis on the biosensor with results obtained against a buffer calibration curve. The assay allowed up to 88 samples to be analyzed per working day, with each cycle on the biosensor taking approximately 7 min to complete. The limit of detection (LOD) was determined as 0.27 ng/mL using 20 EU reference blank urine samples. The intra-assay Sr ranged from 4.7–7.6% for 3 control samples while the interassay Sr ranged from 9.2–12.7%. The recovery was found to be approximately 95%. A series of incurred urine samples were assayed and the results compared by Enzyme immunoassay (EIA), radio-immunoassay (RIA), and gas chromatography/mass spectrometry (GC/MS) analysis.Urine samples taken from local abattoirs were also analyzed by the biosensor method and by EIA analysis. The antibody used in the biosensor test exhibited high cross reactivity with at least 7 other β-agonists allowing detection of these compounds at less than 1 ng/mL in bovine urine.


2013 ◽  
Vol 2013 ◽  
pp. 1-3 ◽  
Author(s):  
Joshua L. Fenderson ◽  
Amy N. Stratton ◽  
Jennifer S. Domingo ◽  
Gerald O. Matthews ◽  
Christopher D. Tan

The aim of this paper is to report the first case of atomoxetine leading to false-positive urine drug screen. An otherwise healthy 27-year-old female with a history of attention deficit hyperactivity disorder (ADHD) treated with atomoxetine had an acute onset tonic-clonic seizure. On arrival to the hospital, a urine toxicological drug screen with immunochemical cloned enzyme donor immunoassay (CEDIA) was performed. Results were positive for amphetamines; however, the presence of these substances could not be confirmed with urine gas chromatography-mass spectrometry (GC-MS). She denied any illicit drug use, herbal medications, or supplements, and her other prescription medications have not been previously known to cause a false-positive result for amphetamines. While stimulant treatments for ADHD could certainly result in a positive result on urine screen for amphetamines, there have been no reports of false-positive results for amphetamines secondary to patients using atomoxetine. We implicate atomoxetine, and/or its metabolites, as a compound or compounds which may interfere with urine drug immunoassays leading to false-positive results for amphetamines CEDIA assays.


2016 ◽  
Vol 54 (6) ◽  
pp. 1566-1572 ◽  
Author(s):  
Alba Abras ◽  
Montserrat Gállego ◽  
Teresa Llovet ◽  
Silvia Tebar ◽  
Mercedes Herrero ◽  
...  

Chagas disease has spread to areas that are nonendemic for the disease with human migration. Since no single reference standard test is available, serological diagnosis of chronic Chagas disease requires at least two tests. New-generation techniques have significantly improved the accuracy of Chagas disease diagnosis by the use of a large mixture of recombinant antigens with different detection systems, such as chemiluminescence. The aim of the present study was to assess the overall accuracy of a new-generation kit, the Architect Chagas (cutoff, ≥1 sample relative light units/cutoff value [S/CO]), as a single technique for the diagnosis of chronic Chagas disease. The Architect Chagas showed a sensitivity of 100% (95% confidence interval [CI], 99.5 to 100%) and a specificity of 97.6% (95% CI, 95.2 to 99.9%). Five out of six false-positive serum samples were a consequence of cross-reactivity withLeishmaniaspp., and all of them achieved results of <5 S/CO. We propose the Architect Chagas as a single technique for screening in blood banks and for routine diagnosis in clinical laboratories. Only gray-zone and positive sera with a result of ≤6 S/CO would need to be confirmed by a second serological assay, thus avoiding false-positive sera and the problem of cross-reactivity withLeishmaniaspecies. The application of this proposal would result in important savings in the cost of Chagas disease diagnosis and therefore in the management and control of the disease.


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