Impact of Lowering Confirmatory Test Cutoff Value in Pre-Enlistment Urine Cannabinoids Screening: About Five Years Experience in the French Gendarmerie

Toxicology Department, Institut de Recherche Criminelle de la Gendarmerie Nationale, Rosny sous bois, France.
Journal of analytical toxicology (Impact Factor: 2.86). 08/2012; 36(8):569-74. DOI: 10.1093/jat/bks067
Source: PubMed


The guidelines for screening of urinary cannabinoids require that all specimens testing positive should be confirmed by gas
chromatography–mass spectrometry at a confirmatory test cutoff value of 15 ng/mL of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol
(THCCOOH). To assess the impact of lowering the confirmatory test cutoff value on the diagnostic sensitivity and efficiency
of a cannabinoid testing program, the results of 986 confirmation analyses of positive screening tests, conducted in the framework
of medical fitness examinations prior to enlistment in the French Gendarmerie between January 1, 2005, and December 31, 2009,
were retrospectively studied. If the confirmatory test cutoff value of THCCOOH is set at 5 ng/mL instead of 15 ng/mL as recommended
by guidelines, the number of confirmed results increases by 25.2%. The positive predictive value of the initial screening
test rises from 63.9 to 80.0%. Only one true-positive applicant has appealed. His THCCOOH urinary concentration, which was
incompatible with passive cannabis smoke exposure, was confirmed by another laboratory. The use of a confirmatory test cutoff
value lower than that recommended significantly increases the diagnostic sensitivity of the screening program for urinary
cannabinoids without altering its specificity.

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    • "If the immunoassay is positive, confirmatory testing is required to definitively establish the identity of the THC-COOH metabolite and report the specimen as positive. Confirmatory testing is performed by GC–MS after enzymatic hydrolysis and liquid–liquid extraction according to the method previously published [17]. Among the 26 unconfirmed cannabinoids screening tests – within 172 confirmatory testing carried out in our laboratory between November 1, 2011, and October 31, 2012 – three patients (one female and two males: respectively 47, 36, 48 years old and 65, 69, 105 kg body weight) have confessed to using regularly methoxyisoflavone to the medical officer. "
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    ABSTRACT: Methoxyisoflavone (5-methyl-7-methoxyisoflavone) is a synthetic isoflavone used by bodybuilders for its ergogenic properties. A recent study demonstrated that methoxyisoflavone metabolites can induce false-positive results in urinary immunoassay screening tests for cannabinoids, and only one metabolite has been identified. To improve the knowledge on the metabolic pathways of methoxyisoflavone, ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF) was applied. Urine samples were obtained from methoxyisoflavone regular users. After enzymatic hydrolysis and liquid-liquid extraction, the samples were analyzed by UPLC-Q-TOF fitted with an electrospray ionization source (ESI) operating under positive ion mode. Mass data were acquired with the MS(E) method. Five metabolites were identified. Those were divided into two metabolic pathways, depending on whether the B ring hydroxylation was preceded or not by the O-demethylation of the methoxy group. The MS(E) mass spectra of methoxyisoflavone and its metabolites are specific of isoflavones structures and revealed 1,3 retro Diels-Alder fragmentation and double CO loss. Losses of small neutral molecules CO and H2O, and radical CH3, typical of flavonoids, were also observed. This study illustrates the capacity of the sensitive UPLC-Q-TOF analytical system, combined with the MS(E) method of collection of fragmentation data, to rapidly elucidate the unknown xenobiotics metabolism.
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    ABSTRACT: Drugs of abuse testing is used in various areas of society for detection and follow-up of drug use. In routine laboratory drug testing, immunoassays are employed for initial screening of specimens to indicate the presence of drugs. To confirm a positive screening test, a secondary analysis by mass spectrometry is performed. The »cut-off« is the pre-defined concentration threshold of a drug or drug metabolite above which the sample is considered positive. A reading below this level implies a negative test result. Swedish drug testing laboratories currently employ varying cut-offs to distinguish between a positive and a negative test result. Because a positive drug test may have serious legal consequences to the individual, it is of importance that testing is performed and judged equally, regardless of where it is performed. A national harmonization of cut-offs is therefore warranted. Based on data from four major Swedish drug testing laboratories, and considering the recommendations in international guidelines, a proposal for national harmonization of urine cut-offs for the most common set of drugs of abuse is presented.
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