Impact of Lowering Confirmatory Test Cutoff Value in Pre-Enlistment Urine Cannabinoids Screening: About Five Years Experience in the French Gendarmerie
ABSTRACT 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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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.Journal of pharmaceutical and biomedical analysis 03/2014; 96C:127-134. DOI:10.1016/j.jpba.2014.03.031