Different analytical procedures for quantitation of total morphine and codeine in urine were evaluated. Hydrolysis of urine with hydrochloric acid and four different enzymes was compared. In order to effect complete hydrolysis of glucuronide conjugates, hydrolysis with 6.5M HCl containing bisulphite and heating at 100 degrees C for 20 min was required. Results using this hydrolysis procedure agreed well with results from direct analysis of free and conjugated forms by liquid chromatography. Use of more dilute HCl but at a higher temperature was not sufficient. Some enzymatic procedures appeared to give effective hydrolysis with a higher variability, but these procedures were more time-consuming. There was a good quantitative agreement between FID gas chromatography and ion-trap gas chromatography/mass spectrometry. The validated analytical procedure was applied to authentic patient samples.

Chromatography, Gas↗

PubMedDate not supplied

Urine and plasma pharmacokinetics of codeine in healthy volunteers: implications for drugs-of-abuse testing.

Thirteen healthy volunteers participating in an open and randomized study received two single doses (25 and 50 mg) of codeine orally two weeks apart. Urine concentrations of opiates were studied for 96 h, and plasma concentrations of codeine and the metabolites codeine-6-glucuronide (C6G), morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were monitored for 24 h. Plasma was analyzed by high-performance liquid chromatography. Measurements of urine were made with the EMIT opiate-screening assay and with gas chromatography-mass spectrometry for total (conjugates liberated by acid hydrolysis) codeine, morphine, and norcodeine. In urine, the ratio between total recovered morphine and codeine as expressed in percent ranged from 2.3 to 23.3% with a mean value of 9.8%. This ratio increased with time, and, in all but three subjects, rose to greater than 1 after 22-36 h. In 58% of cases, this occurred within the detection time in the EMIT assay. The detection time in the EMIT screening assay was found to be 20-39 h after the 25-mg dose and 30-52 h after the 50-mg dose. Elimination rates calculated from urine data corrected for creatinine concentration showed that morphine was eliminated more slowly than codeine. In plasma, the highest concentrations and area-under-curve values were observed for C6G, followed by codeine and M3G. All compounds had peak plasma values 1-2 h after dosing. The elimination of M3G was slower than that of C6G. We concluded that the relative proportion of codeine and morphine varies both between individuals and as a function of time and that morphine may be present in concentrations above those of codeine even after moderate and single doses of codeine. This must be taken into consideration when interpreting the presence of opiates during drugs-of-abuse testing.

Administration, Oral↗

PubMedDate not supplied

A GC-MS study of three major acidic metabolites of delta 1-tetrahydrocannabinol.

The major urinary metabolite of delta 1-tetrahydrocannabinol (delta 1-THC) (1), delta 1-THC-7-oic acid (2), has been extensively studied for several purposes, including testing in the workplace for drug abuse. Immunoassays in combination with more specific methods such as gas chromatography-mass spectrometry (GC-MS), are commonly used for verification of positive results in the screening. Two additional and recently synthesized acidic metabolites of 1, 4",5"-bisnor-delta 1-THC-7,3"-dioic acid (3) and 4"-hydroxy-delta 1-THC-7-oic acid (4), were studied to widen the scientific basis in the analysis. Five different derivatives were examined using GC-MS. In addition, a new deuterated internal standard for 2, [2H10]-2, was evaluated. According to our results, suitable derivatives of 2, 3, and 4, according to chromatographic properties, are the methyl ester/silyl ether (procedure a), the methyl ester/trifluoroacetate (procedure b), or the silyl ester/silyl ether (procedure c). The estimated recoveries of [2H5]-3 and [2H6]-4 using liquid-liquid extraction were 24% and 50%, respectively. The properties of [2H10]-2 as internal standard were equivalent to those of [2H9]-2 and, under the conditions used, did not appear to give rise to a significantly higher chromatographic resolution from that of 2. However, [2H10]-2 produces ions at different mass numbers, which makes it useful as a complement to the existing deuterated internal standards of 2.

Dronabinol↗

PubMedDate not supplied

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

Presence of phenylethylamine in hallucinogenic Psilocybe mushroom: possible role in adverse reactions.

The use of mushrooms containing the hallucinogenic substance psilocybin for intentional intoxication is relatively common. Occasionally, this results in adverse reactions with typical tachycardia that is not evidently caused by psilocybin. This study demonstrates the presence of phenylethylamine in the species Psilocybe semilanceata using gas chromatography-mass spectrometry and shows that the amount of this substance may vary much more than that of psilocybin. The highest amount of phenylethylamine (146 microg/g wet weight) was observed in mushrooms from a case of three young men hospitalized because of adverse reactions. Comparison of the symptoms observed in clinical cases of magic mushroom intoxication with those after intake of pure psilocybin or phenylethylamine suggests that phenylethylamine might have a role in the development of adverse reactions to Psilocybe mushroom intake.

Adult↗

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↗

PubMedDate not supplied

The role of sedation in ERA from the vertex.

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Anesthesia↗