TRITIUM ANALYSIS IN URINE BY THE TRIPLE-TO-DOUBLE COINCIDENCE RATIO METHOD WITH THE HIDEX 300 SL LIQUID SCINTILLATION COUNTER.

The triple-to-double coincidence ratio (TDCR) method is a liquid scintillation primary method for the absolute activity measurement of pure ß- and pure electron capture emitters. This method requires specific three-photomultiplier liquid scintillation counters. The aim of the present work is to assess the TDCR method performance for routine tritium analysis in urine using an HIDEX 300 SL, the only three-photomultiplier liquid scintillation counter designed for routine laboratories. The physical parameters and the semi-empirical Birks parameter (kB) of the prepared liquid scintillation source were firstly determined. TDCR model equations solving and detection efficiencies calculations for measured samples were performed by TDCR07c computing program. Accuracy, uncertainties and detection limit of TDCR method were assessed through the tritium analysis of six intercomparison urine samples. The results demonstrate that the analytical performance of the TDCR method implemented on the HIDEX 300 SL is conform to the recommendations for the monitoring of workers exposed to tritium.

RECOMMENDATIONS FOR MONITORING AND INTERNAL DOSIMETRY FOR NUCLEAR MEDICINE STAFF EXPOSED TO RADIOPHARMACEUTICALS 223Ra DICHLORIDE.

223Ra is a radiopharmaceutical used as unsealed source in nuclear medicine. In the case of staff inhalation contamination of 223Ra, methods to estimate the committed effective dose should be chosen with care. Three methods are available: whole-body measurement and gamma spectrometry for urine or faeces samples. Considering the analytical performances and uncertainties of these three methods, we propose recommendations for special dose assessment. As a first choice, due to its rapidity and its non-invasiveness, an in vivo analysis (with HPGe detector) is the most appropriate method. However, after 24 h, whole-body counting is not sensitive enough to detect a minimum effective dose of 1 mSv. Sufficient sensitivity can only be reached up to 8 days after contamination by true 24 h faeces samples analyses. Thus, despite its main drawbacks, this method appears to be more appropriate than urine to estimate the committed effective dose in addition to whole-body counting.

DosiKit, a New Portable Immunoassay for Fast External Irradiation Biodosimetry.

DosiKit is a new field-radiation biodosimetry immunoassay for rapid triage of individuals exposed to external total-body irradiation. Here, we report on the validation of this immunoassay in human blood cell extracts 0.5 h after in vitro exposure to 137Cs gamma rays, using γ-H2AX analysis. First, calibration curves were established for five donors at doses ranging from 0 to 10 Gy and dose rates ranging from ∼0.8 to ∼3 Gy/min. The calibration curves, together with a γ-H2AX peptide scale, enabled the definition of inter-experimental correction factors. Using previously calculated correction factors, blind dose estimations were performed at 0.5 h postirradiation, and DosiKit performance was compared against concomitant dicentric chromosome assay (DCA), the current gold standard for external irradiation biodosimetry. A prototype was then assembled and field tested. We show that, despite significant inter-individual variations, DosiKit can estimate total-body irradiation doses from 0.5 to 10 Gy with a strong linear dose-dependent signal and can be used to classify potentially exposed individuals into three dose ranges: below 2 Gy, between 2 and 5 Gy and above 5 Gy. The entire protocol can be performed in 45 min, from sampling to dose estimation, with a new patient triaged every 10 min. While DCA enables precise measurement of doses below 5 Gy, it is a long and difficult method. In contrast, DosiKit is a quick test that can be performed directly in the field by operational staff with minimal training, and is relevant for early field triage and identification of individuals most likely to experience acute radiation syndrome. These findings suggest that DosiKit and DCA are complementary and should be combined for triage in a mass scale event. While the proof-of-concept reported here validates the use of DosiKit at 0.5 h postirradiation, further studies are needed to calibrate and evaluate the performance of the DosiKit assay at longer times after irradiation.

EURADOS intercomparison on emergency radiobioassay.

Nine laboratories participated in an intercomparison exercise organised by the European Radiation Dosimetry Group (EURADOS) for emergency radiobioassay involving four high-risk radionuclides ((239)Pu, (241)Am, (90)Sr and (226)Ra). Diverse methods of analysis were used by the participating laboratories for the in vitro determination of each of the four radionuclides in urine samples. Almost all the methods used are sensitive enough to meet the requirements for emergency radiobioassay derived for this project in reference to the Clinical Decision Guide introduced by the NCRP. Results from most of the methods meet the requirements of ISO 28218 on accuracy in terms of relative bias and relative precision. However, some technical gaps have been identified. For example, some laboratories do not have the ability to assay samples containing (226)Ra, and sample turnaround time would be expected to be much shorter than that reported by many laboratories, as timely results for internal contamination and early decisions on medical intervention are highly desired. Participating laboratories are expected to learn from each other on the methods used to improve the interoperability among these laboratories.

UPLC-ESI-Q-TOF-MS(E) identification of urinary metabolites of the emerging sport nutrition supplement methoxyisoflavone in human subjects.

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.

[Interest and limits of inductively coupled plasma mass spectrometry (ICP-MS) for urinary diagnosis of radionuclide internal contamination]. / Intérêt et limites du couplage plasma induit par haute fréquence - spectrométrie de masse (ICP-MS) pour le diagnostic urinaire d'une contamination interne par un radionucléide.

After a review of radiometric reference methods used in radiotoxicology, analytical performance of inductively coupled plasma mass spectrometry (ICP-MS) for the workplace urinary diagnosis of internal contamination by radionuclides are evaluated. A literature review (covering the period from 2000 to 2012) is performed to identify the different applications of ICP-MS in radiotoxicology for urine analysis. The limits of detection are compared to the recommendations of the International commission on radiological protection (ICRP 78: "Individual monitoring for internal exposure of workers"). Except one publication describing the determination of strontium-90 (ß emitter), all methods using ICP-MS reported in the literature concern actinides (α emitters). For radionuclides with a radioactive period higher than 10(4) years, limits of detection are most often in compliance with ICRP publication 78 and frequently lower than radiometric methods. ICP-MS allows the specific determination of plutonium-239 + 240 isotopes which cannot be discriminated by α spectrometry. High resolution ICP-MS can also measure uranium isotopic ratios in urine for total uranium concentrations lower than 20 ng/L. The interest of ICP-MS in radiotoxicology concerns essentially the urinary measurement of long radioactive period actinides, particularly for uranium isotope ratio determination and 239 and 240 plutonium isotopes discrimination. Radiometric methods remain the most efficient for the majority of other radionuclides.

Impact of lowering confirmatory test cutoff value in pre-enlistment urine cannabinoids screening: about five years' experience in the French Gendarmerie.

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.

[Metachlorophenylpiperazine (mCPP): a new designer drug]. / La métachlorophénylpipérazine (mCPP) : une nouvelle drogue de synthèse.

Metachlorophenylpiperazine (mCPP) is a psychoactive substance that appeared in 2004 on the black market of illicit substances in Europe and France. It has a strong affinity for serotoninergic receptors and the serotonin transporter. In humans, mCPP induces endocrine, neurological and psychiatric effects. Its subjective effects are similar to those of amphetamines. However, drug-users allot few positive subjective effects. Reported cases of intoxication are generally not serious but the risks of psychiatric disorders and serotoninergic syndrome must be taken into account. Risk factors of the intoxication to mCPP are the existence of predisposing psychiatric pathologies and pharmacodynamic or metabolic interactions. mCPP does not exhibit reinforcing effects. mCPP is not the subject of any international regulation: procedures of medical and social risk assessment were implemented in European and the national levels.