Total radioactivity

EoUowing po administration moricizine is completely absorbed from the GI tract. The dmg undergoes considerable first-pass hepatic metabolism so that only 30—40% of the dose is bioavailable. Moricizine is extensively (95%) bound to plasma protein, mainly albumin and a -acid glycoprotein. The time to peak plasma concentrations is 0.42—3.90 h. Therapeutic concentrations are 0.06—3.00 ]l/niL. Using radiolabeled moricizine, more than 30 metabolites have been noted but only 12 have been identified. Eight appear in urine. The sulfoxide metabolite is equipotent to the parent compound as an antiarrhythmic. Elimination half-life is 2—6 h for the unchanged dmg and known metabolites, and 84 h for total radioactivity of the labeled dmg (1,2). 

It is important to note that since the amounts of radioactive material produced are so extremely small (some 10 % of the total is typical) it is usually necessary to add macro quantities—10-100 mg—of each compound expected to be present, in order to effect a good separation and to measure the chemical yield of the carrier. The yield measured is the radioactivity in each separated chemical species as a fraction of the total radioactivity in the sample, corrected to 100% chemical yield of each respective carrier. The term retention is commonly used to refer to the yield of the parent compound. This term has the disadvantage, however, of implying that the radioactive atom remained in the same molecule. Since it often appears that the molecule is only later reconstituted, the terms yield and parent yield are to be preferred. 

The total radioactivity, Ag, of a specified nuclide in a target containing N atoms of the appropriate isotope, irradiated in a flux, /, of neutrons for t seconds and allowed to decay for T seconds after the end of the irradiation, is given by... 

In subsequent smdies, it was shown that, atfer hydrolysis, about 42% of the total radioactive residue in grain may be identified as 4-fert-butylcyclohexanone. Moreover, 34-90% of the TRR was extracted by heating the plant material under reflux with a mixture of methanol and hydrochloric acid. The performance of that method was properly demonstrated by individual fortification experiments with the parent compound and the three primary metabolites (bold in Figure 1). 

Validation of true extraction efficiency normally requires the identification and quantitation of field-applied radiolabeled analyte(s), including resulting metabolites and all other degradation products. The manufacturer of a new pesticide has to perform such experiments and is able to determine the extraction efficiency of aged residues. Without any identification of residue components the calculation of the ratio between extracted radioactivity and total radioactivity inside the sample before extraction gives a first impression of the extraction efficiency of solvents. At best, this ratio is nearly 1 (i.e., a traceability of about 100%) and no further information is required. Such an efficient extraction solvent may serve as a reference solvent for any comparison with other extraction procedures. 

Often solvents do not extract 100% of the total radioactive residue. In this case, knowledge about the concentration of the target analyte(s) in the extract and the filter cake is necessary. Even if large amounts of radioactivity remain in the solid residual materials, the extraction efficiency may be sufficient if this unextracted radioactivity is permanently bound to the matrix or if it is associated with compounds which are not included in the residue definition. Finally, in all cases a well performed metabolism study can provide the answers needed, even where residues in the edible parts of treated crops or animals do not occur. If incurred residues do not occur, clearly the determination of extraction efficiency is not required. 

The total radioactivity in serum (PCP and metabolites) increased significantly after Fab administration (figure 4). This increase was mostly due to the dramatic increase in unchanged PCP concentration and not due to an increase in metabolite concentration. 

Less than 1% of total radioactivity was found in tissues 6 18 hours after oral administration of [14C]tributyl phosphate. The majority of label was found in urine (70%) and feces (18%) after both single and multiple doses of 10 and 350 mg/kg/day (Gatz 1992b). Approximately 5% of the label was recovered as C02 in expired air. 

The negligible intestinal absorption of rifaximin was subsequently confirmed with the use of the labeled drug. After oral administration in rats the total radioactivity present in plasma was found to be no more than 0.1 and 2% of the administered dose after the intake of 3H-labeled [99] and 14C-labeled [59] compound, respectively. 

Typical validation for radiochemical and radiopharmaceutical purity. Quality control is very important to ensure the safety and efficacy of radiopharmaceuticals. One important quality parameter is the radiochemical purity of the radiolabeled product. This is defined as the fraction of the total radioactivity in the desired chemical form in the radiopharmaceutical [56]. Radiochemical impurities come from incomplete labeling, shift of equilibrium, radiolysis ((3 decay), temperature or pH change, exposure to light,... 

Fingerlings were fed a diet containing radiosilver-110m for 34 days then fed a clean diet for 27 days After 34 days, about 12% of the silver fed was retained liver contained 63% of the total radioactivity. After 27 days of depuration 31% of the radiosilver was lost from whole trout, but liver contained 79% of the total radioactivity 36... 

After 72 h, bile contained 25% of the total radioactivity major BaP metabolites were glucuronides (54%), sulfates (12%), and unmetabolized BaP(14%). The potentially genotoxic metabolite BaP-7,8-dihydrodiol and its glucuronide represented 0.7 and 2.0%, respectively, of the bile radioactivity BaP and chrysene were most efficient in elevating EROD activities, cytochrome P-4501 A protein levels, and total cytochrome P-450 content 1-14 days postinjection. Less pronounced increases were caused by fluoranthene and pyrene B[gh/]PER did not affect these parameters... 

Fig. 9 In vitro metabolism of pyrethroid metabolites in leaf cell suspension of cabbage (C) and tomato (T). The values in parentheses are percent of the total radioactive residues in leaf cell extract/medium after 1-day incubation, nd not detected...

When rainbow trout were transferred to fresh water (24+24 and 24+48 in Table III), both fenitrothion and its radioactive metabolites were eliminated from the fish. Thus after 48 hr in fresh water, 60% of the radioactivity originally contained in the fish had been excreted into the water and the degradation products accounted for one half of the total radioactivity in water. Fenitrothion in the fish biomass steadily decreased, although the rate was lower than in running water as will be described belcw. 

In another trial, at 7 days after building-up the ecosystem, 10 ppb equivalent of the radioactive fenitrothion was added to water. Ten ppb of carbon-14 fenitrothion was added 3 times at the interval of one week. The system was kept at 25°C in a green house. An aliquot of water was sampled periodically, and the content of total radioactivity as well as fenitrothion was monitored. 

Table V, VI and VII summarize the results of identification of the degradation products. The total radioactivity as well as intact fenitrothion decreased in snail and fish, and 3 consecutive applications of fenitrothion did not affect these concentrations very much. In contrast, in daphnids and in algae total radioactivity tendfed to increase with the lapse of time, mostly due to an increase of unextractable radioactivity and unidentified products, although the fenitrothion content was constantly decreasing...

Of the total radioactivity in fish, ether extracted 78.26, petroleum ether 10.79, and methanol 10.95%. Percent composition of each of these fractions is shown in vertical column. 

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