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The online screening technique for urinary benzodiazepines: comparison with EMIT, FPIA, and GC-MS.

Three commercial immunoassay systems (EMIT, EPIA, Online) for the screening of benzodiazepines in urine were evaluated using authentic patient samples with gas chromatography-mass spectrometry (GC-MS) as the reference method. The Online system (kinetic interaction of microparticles in solution) gained in performance by applying a 100-ng/mL cutoff limit and by incorporating beta-glucuronidase treatment, which could be automated on the Cobas Mira Plus instrument. When using enzymatic hydrolysis, all three immunoassay systems had high levels of sensitivity, including samples containing only flunitrazepam and nitrazepam metabolites. A high degree of concordance was observed between the Online and FPIA (fluorescence polarization immunoassay) systems when analyzing 138 randomly selected patient samples. The EMIT II and EMIT d.a.u. (enzyme multiplied immuno technique) systems gave a higher number of positive results, but the presence of benzodiazepines could not be verified by GC-MS in a substantial number of these cases. The rate of unconfirmed positive results was increased when enzyme hydrolysis was incorporated in the EMIT II assay. Although differences in the performances of the investigated assay systems were observed, they all seem appropriate for clinical use in detecting benzodiazepine intake in drug abusers when enzymatic hydrolysis is included.

Benzodiazepines↗

PubMedDate not supplied

Morphine formation from ethylmorphine: implications for drugs-of-abuse testing in urine.

In drugs-of-abuse testing, opiates constitute a delicate and controversial task because morphine may occur in urine for several reasons. Ethylmorphine (EtM), which is used as an antitussive drug in many countries, is metabolically converted to morphine. The present study was performed in order to document intra- and interindividual differences in morphine formation after single-dose intake of EtM at two different doses (25 and 50 mg). The urinary excretion of opiates was measured during 48 h with EMIT and gas chromatography-mass spectrometry in 10 healthy volunteers. The mean values of totally recovered EtM and morphine in hydrolyzed urine during 48 h were 42 and 47% of the given dose at high and low dose level, respectively. The ratio between total recovered morphine and EtM ranged from 19 to 131% with a mean value of 48%. The rate of positive outcome in the EMIT opiate-screening assay was 100% during the first 24 h for both doses, and it was still high (> or = 67%) in the 24-48 h time interval. It was found that the decline in urinary EtM is more rapid than for morphine, which leads to an increasing morphine/EtM ratio in urine over time. THe mean value of the morphine/EtM ratio was found to be greater than 1 during the 12-24 h interval and finally increased to greater than 10. There was an intra-individual concordance in morphine/EtM ratio between doses, but there was marked interindividual variation. Morphine/EtM ratios that were greater than 1 were only seen when the concentration of morphine was below 300 micrograms/mmol creatinine. Our results demonstrate that morphine is formed from EtM at a high and variable rate and may be present in urine in concentrations greater than those of EtM even shortly after drug intake.

Adult↗