Document 44nwJnER6o6RDZ4RyKeNR79vj
Extent and Route of Excrettiioonnaqnw@@ u Distribution of Total Carobotnn- in Rats after a Single Intravenous a .of pC-95-14C
December 28, 19
30@_OGY
Conducted at: During: Conducted by: Report by:
Reviewed by:
Riker Laboratories Inc., Subsidiary of 3M St. Paul, Minnesota 55101
June to October, 1979
S. J. Gibson and J. D. Johnson
s D. Jo on, M.S.
ri(ate
enior Bio@,@- cal Pharmacologist
? =O2s1r@E
ert E. Ober, Ph.D. Manager, Drug Metabolism
Date
77
Summary
-2-
By 89 days after a single iv dose of FC-.95-14C(mean dose, 4.2 mg/kg) six male rats excreted a mean of 30.2% of the total carbon-14 via urine. Mean
cumulative fecal excretion was 12.6%. At 89 days, mean tissue concentration of total carbon-14 expressed as Ug FC-95-14C equivalents/gwere: liver, 20.6; plasma, 2.2; kidney, 1.1; lung, 1.1; spleen, 0.5; and bone marrow,
0.5. Lower concentrations (< 0.5) were measured in adrenals, skin, testes, muscle, fat, and eye. No razioactivity(< 0.05) was detected in brain. The carbon-14 in liver and plasma represents 25 and 3 percent of the dose, respectively.
Introduction
F
c F *c-so
7 15
3
* Denotes position of carbon-14
FC-95 is the potassium salt of a perfluorinatedsulfonic acid. A series of experiments has been planned to investigatepossible means of increasing the rate of elimination of FC-95 from the body. FC-95 absorption, elimination from plasma, and excretion data were neces ary to form a basis for efficient design of these experiments. This FC-95-'ZC intravenousexperiment (FCExperiment 3) which was designed to provide data on the route and extent of total carbon-14 excretion was paired with an FC-95-14 C oral dosing experiment which was designed to provide data on total carbon-14 absorption and elimination from plasma. (2) In addition, these FC-95 absorption, plasma elimination,and excretion data will be used to interpretand guide other experiments on the possible biotransformationof FC-807 (3) to FC-95.
Methods
Radiolabeled FC-95-14C
The carbon-14 label is at the position a to the sulfur atgm (see above structure). The specificactivityof this lot of @@-95-'qC (Riker Isotope Inventory Number 442) is 0.459 uCi/mg. The FC-95- C was found to be suitable for metabolism studies; details of the synthesis,specificactivity determination, and radiochemical purity determination have been reported. (1)
Animals
Six male Charles Rivera CD rats, eight weeks old, were conditioned to individual metal metabolism cages for 24 hours prior to dosing. The body weights ranged from 262 to 303 g, mean 288 g. The rats were allowed free access to Purina-bGround Chow and water before and after dosing.
Dosing
Each rat was weighed, anesthetized with diethyl ether, and then given a single iv dose (via tail vein) of FC-95-14C. The dose was 2.0 ml of a 0.9% NaCi solution containing 1.21 mg FC-95-14C/2.0mi. The average dose was 4.2 mg/kg. The dose was delivered with a 3.0 cc disposable plastic syringe (Monoject6S) fitted with a 26 gauge 1/2" needle. The
Charles River Breeding Laboratories, Wilmington, Mass. Purina Lab Chow, Ralston Purina Company, St. Louis, Missouri. Sherwood Medical Industries, Inc., Deland, Florida 32720.
-3-
dosing solution was prepared by adding 96200 mg of FC-95-14 C to 0.9% NaC), shaking for one-half hour at moderate speed in a mechanical shaker, and centrifuging. The supernatantwas removedand used for dosing solution. The carbon-14 content of the dosing solution was determined'by direct counting (seeAppendix 1).
Sample Collection
Urine and feces were collected at intervals(seeTables I and 2) for each of the six rats for 89 days. At 89 days post dose,the ratswere anesthetized with diethylether;bloodwas drawn from the descending aortaand immediately transferredto a heparinizedtube. Plasma was prepared promptlyby centrifugation. The rats were sacrificedby axsanguination;and spleen, liver,brain, testes,adrenals,kidneys,lungs, and eyes were collected as whole organs. Bone marrow was obtained from the four major bones of the rear legs by splittingthe bone and collectingthe marrow on pieces of a tared combustion pada-. Samples of skin, thigh muscles, subcutaneousand abdominalfat, and the total remainingcarcass were collected.
Sample Analysis for Carbon-14
Feces and major organs were prepared for carbon-14 analysis by homogenizing and aliquoting a sample of the homogenate into combustion cone@@. Homogenizingwas done in Waring blendersby adding nine parts of water (wlw) to one part of biological material. The homogenateswere weighed into combustioncones in triplicateon a top-loadingbalance by taring the cone and adding 1.0 9 of the homogenate. Care was taken to mix the homogenate between samplings. Urine, red blood cells, and plasma were measured into combustion cones by weight. Whole eyes, adrenals, and samples of bone marrow, skin and fat were also weighed in combustion cones. Care was taken to weigh these samplespromptly (1-2 minutes)after removal in order to avoid loss of weight by drying. Homogenates,tissue samples weighed directly, and weighed samples of plasma, red blood cells, and urine were combustedwith a Packard Model 306 Oxidizer. Recovery of carbon-14 from biological samples was determined by combusting suitable blank homogenates(feces, liver, musci and spleen)and blank rat plasma spikedwith dilutionsof FC-95-T4 C dosing solutionat the beginning, middle,and end of the experimentalsample set (seeAppendix 2). Urine collectionswere sampled before freezingand were counted directly; triplicate1.0 mi aliquotsof each samplewere pipetteddirectly into scintillationvials and 15 ml Aquaso]Owas added. All sampleswere cooled to refrigeratortemperaturein the dark before counting. All radiometric analyseswere done using a Packard Model 3385 Tri-Carb Liquid Scintillation Spectrometer.
Counting efficiency for each sample was determined by use of the AES (Automatic ExternalStandardization)ratio method. To calibratethe external standard, internal standardwas added to selected samples from the group of samples (threewith low AES ratios and three with high ratios),and these samples were recounted along with a sealed standard. Data were collected on punch tape and processed by the CDC 1700 Computer System in the 3M Central Research Data Processing Laboratory. Data reduction to dpm was accomplishedwith the BiologicalAutomatic External Standardization computer program.
Packard InstrumentCompany, Inc., 2200 Warrenville Road, Downers Grove, IL.
-4-
Results and Discussion
The results of the fecal and urinary analyses are shown in Tables I and 2 and in Figures I and 2. Tables I and 2 list the total carbon-14 expressed as percent of dose. The data are expressed as cumulative percent of dose excreted versus time in Figures I and 2. As illustrated in Figures I and 2, excretion of total carbon-14 is slow. By 89 days after dosing, total excretion (urine + feces) is only 43 percent of the dose. Radioactive content in feces was too low to measure after 64 days; total carbon-14 excreted is thus the sum of fecal excretion (o to 64 days) and urinary excretion (0 to 89 days). The mean ratio of cumulative excretion of total carbon-14 in urine (30.2%) to that in feces (1.2.6%)was 2.4 t 0.2. This is in contrast to the ratio of cumulative excretion of total carbon-14 in urine to that in feces (< 0.1)at 124 days post dose reported after a single iv dose of FC-807-14C-.(3) Tibisindicates that FC-807-14 C is not likely extensively biotransformed to FC-95-14C. Since 50-60 percent of the FC-95-14C dose was not excreted by either feces or urine at 89 days post dose, selected tissues were analyzed for carbon-14 content to identify those tissues in which total carbon-14 might be retained.
The results of the tissue analyses are shown,4n Table 3. Mean tissue carbon-14 concentrations above one Ug FC-95- C equivalents/g were as follows: liver, 20.6; plasma, 2.2; kidney, 1.1; and lung, I.I. Other tissues such as muscle, skin, bone marrow, and spleen had concentrations ranging from 0.2 to 0.6 ug/g. There was a difference in carbon-14 content of subcutaneous fat (0.2 pg/g) and abdominal fat (< 0.08pg/g). Very little total carbon-14 was found in whole eye (0.16 ug/g) and no detectable total -carbon-14 was found in brain. There is a strikingdifference in the pattern of total carbon-14 etention when liver, bone marrow, and spleen after iv dosing with FC-95-1 C is compared to thq,pattern of retention found for these tissuez after dosing with FC-807-'4C. (3) The mean carbon-14 content for FC-807-1 C dosed rats normalized to liv r-c@ntent are: liver, 1.0; spleen, 8.9; and bone marrow, 2.4. For FC-;5 1 C dosed rats, the mean ratios are liver, 1.0; spleen, 0.02- and bone marrow, 0.02. Since the spleen/liver ratio following FC-95-14C is 8.9 and bone marrow/liver is 2.4, this data supports the conclusion that FC-807 is not extensively or rapidly biotransformed to FC-95.
The total carbon-14 contents expressed as percent of dose for selected whole organs and plasma and red blood cells are listed in Table 4. Only liver and plasma contain a substantial percentage of the dose at 89 days post dose. The low levels of radioactivity found for kidney, lung, testes, and spleen, are (in view of the relatively high carbon-14 content of plasma and red blood cells) due in part to the blood still contained in these organs when homogenized and analyzed.
References
(1) Johnson JD, Behr FE: Synthesis and Characterization of FC-95-14C (Report), November 2. 1979.
(2) Johnson JD: Absorption of FC-95-14C in Rats After a Single Oral Dose (Report) October 26, 1979.
(3) Johnson JD:
. Extent and Route of Exeretiofiand Tissue Distribution
of Total Carbon-14 In Rats After a Single IV Dose of FC-807-14C
(Report), September 28, 1979.
(4) Altman PL, Dittmer DS: Blood and 0 her BodX Fluids. Bethesda,
Maryland, Federation of Pimrican So leties for E 1971, P. 5.
imental Biology,
List of Tables and Figures
Table 1:
Excretion of Total Carbon-14 in Urine in Rats after a Single Intravenous Dose of rC-95-14C (mean Dose* 4.2 mg/kg).
NB 52584 p. 17.
Table 2:
Excretion of Total Caxbon-14 in Feces in Rats after a Single Intravenous Dose of FC-95-14C (Mean Dose, 4.2 mg/kg). NB 52584 p. 14.
Table 3:
Tissue Distribution of Total Cark>on-14 in Rats at 89 Days after a Single Intravenous Dose of FC-95-14C (Mean Dose, 4.2 mg/kg). NB 52584 p. 20.
Table 4:
Percent of Dose Present in Tissues at 89 Days after a Single Intravenous Dose of pC-95-14C (Mean Dose, 4.2 mg/kg). NB 52584 p. 21.
Figure 1:
Cumulative Excretion of Total Carbon-14 in Urine after a Single
IV Dose of FC-95-14C (Mean Dose, 4.2 mg/kg) Mean of 6 Rats. NB 52584 p. 18.
Figure 2:
Cumulative Excretion IV Dose of FC-95-14C NB 52584 p. 14.
of Total Carbon-14 in Feces after a Single (Mean Dose, 4.2 mg/kg) Mean of 6 Rats.
Appendix, Table 1:
Determinat-ion of Carbon-14 Content of Dosing Solution. NB 51312 p. 35.
Appendix, Table 2:
Recovery of Total Carbon-14 from Blank Samples Spiked with FC-95-14C.
NB 52584 p. 16.
Fecal
Homogenate
Appendix, Table 3:
Comparison of Carbon-14 Analysis of 'Urine Samples by Oxidation Versus Direct Counting in Aquasollt. NB 52584 p. 9.
Excretion of Total Carbon-14 in Urine in Rats after a Single Intravenous Dose
of pC-95-14C (mean Dose, 4.2 mgag)
collection
Period(days)
0-0.5
0.5-1 1-2 2-3 3-4 4-5 5-6 6-7 7-8
8-9 9-10 10-11
11-12 12-13 13-14 14-15 15-16 16-17 17-18 18-19 19-21 21-23 23-25 25-27 27-29 29-32 32-36 36-40 40-43 43-47
47-50
50-54 54-57 57-61 61-69 69-78 78-89
1
i.os@@-
0.70 1.56 1.31 1.16 1.09 0.86 1.07 0.90
0.86 0.82 0.60
0.62 0.56 0.55 0.65 0.54 0.57 0.53 0.41 0.93 0.91 0.63 0.76 0.73 1.04 1.06 0.97 0.59 0.59
0.70
0.52 0.63 0.56 1.38 1.51 1.59
TOTAL 31.6
2
0'69
0:90 1.11 1.05 0.87 0.80 0.72 0.71 0.69
0.57 0.66 0.36
0.52 0.53 0.53 0.51 0.48 0.43 0.40 0.39 0.81 0.75 0.59 0.67 0.66 0.88 1.05 1.08 0.58 0.78
0.52
0.77 0.56 0.82 1.33 1.77 2.03
28.6
Rat
3
1.03
0.72 1.47 1.14 1.06 0.81 0.67 0.75 0.85
0.70 0.79 0.65
0.54 0.63 0.51 0.46 0.56 0.40 0.34 0.28 0.79 0.69 0.59 0.64 0.73 0.69 1.16 0.97 0.88 1.00
0.66
0.82 0.62 0.74 1.41 1.49 1.97
Number
4
0.77
0.60 0.78 0.68 0.68 0.60 0.49 .0.52 0.54
o.60 0.59 0.64
0.69 0.60 0.58 0.57 0.45 0.45 0.35 0.42 0.77 0.77 0.66 0.66 0.68 0.89 1.21 1.01 0.82 0.94
0.70
0.83 0.63 0.89 1.64 1.60 2.06
30.2
28.4
5
1.03
0.77 1.08 0.91 0.93 0.80 0.76 0.74 0.76
0.68 0.48 0.63
0.55 0.60 0.57 0.55 0.58 0.48 0.49 0.38 0.84 0.66 0.70 0.68 0.66 0.82 1.14 1.01 0.79 0.96
0.69
0.75 0.58 0.81 1.66 1.64 2.45
30.6
6
0.86
0.94 1.27 1.11 0.85 0.90 0.77 0.75 0.74
0.67 0.74 0.64
0.57 0.59 0.55 0.51 0.46 0.55 0.44 0.46 0.92 0.88 0.77 0.64 0.64 0.86 0.66 0.91 0.83 1.25
0.79
0.98 0.61 0.94 1.59 1.81 2.39
31.8
Mean
0.91
0.77 1.21 1.03 0.93 0.83 0.71 0.76 0.75
0.68 0.68 0.59
0.58 0.59 0.55 0.54 0.51 0.48 0.43 0.39 0.84 0.78 0.66 0.68 0.68 0.86 1.05 0.99 0.75 0.92
0.68
0.78 0.61 0.79 1.50 1.64 2.08
30.2
2@Data are expressed as percent of dose excreted during collection period.
Collection Period (days)
0-0.5 0.5-1
1-2 2-3 3-4 4-5 5-6 6-7 7-8 8-9 9-10 10-11 11-12 12-13 13-14 14-15 15-16 16-17 17-18 18-19 19-21 21-23 23-25 25-27 27-29 29-32 32-36 36-50 50-64
1
0.0432@ 0.711 0.955 0.761 0.736 Or.764 0.636 0.560 0.539 0.441 0.478 0.524 0.311 0.319 0.351 0.328 0.291 0.246 0.228 0.124 0.378 0.357 0.088 0.288 0.266 0.270 0.570 1.397 1.086
TOTAL
14-0
Table 2
Excretion of Total Carbon-14 in Feces in Rats after a Single Intravenous Dose of FC-95-14C (mean Dose, 4.2 mgag)
2
0.780 0.770 0.572 0.604 0.630 0.595 0.464 0.423 0.336 0.400 0.407 0.278 0.279 0.255 0.233 0.276 0.174 0.130 0.105 0.274 0.258 0.349 0.176 0.140 0.114 0.366 1.074 0.663
11.1
Rat Number
3
4
0.069 0.919 0.865 0.726 0.599 0.606 0.352 0.911 0.832 0.597 0.342 0.327 0.240 0.301 0.280 0.265 0.276 0.174 0.171 0.170 0.295 0.280 0.294 0.138 0.197 0.220 0.490 l.S62 0.957
0.004 0.988 0.465 0.466 0.667 0.395 0.397 0.434 0.306 0.337 0.299 0.295 0.304 0.363 0.299 0.309 0.252 0.176 0.156 0.111 0.294 0.303 0.255 0.204 0.181 0.260 0.646 1.768 1.125
13-5
12.1
5
0.178 0.777 0.682 0.6S2 0.639 0.538 0.502 0.522 0.343 0.411 0.371 0.294 0.269 0.300 0.222 0.247 0.252 0.190 0.117 0.110 0.325 0.276 0.280 0.218 0.149 0.239 0.587 1.352 0.452
11.5
6
0.877 1.032 0.719 0.689 0.529 0.578 0.635 0.451 0.401 0.433 0.372 0.374 0.296 0.278 0.275 0.283 0.164 0.178 0.153 0.301 0.340 0.308 0.226 0.280 0.237 0.499 2.028 0.712
13.6
Mean
0.049 0.842 0.795 0.649 0.656 0.577 0.510 0.588 0.482 0.421 0.387 0.370 0.296 0.310 0.281 0.276 0.272 0.187 0.163 0.129 0.311 0.302 0.262 0.208 0.202 0.223 0.526 1.530 0.833
12.6
Data are expressed as percent of dose excreted during collection period.
-9-
Table 3
Tissue Distribution of Total Carbon-14 in Rats at 89 Days after a Single Intravenous
Dose of FC-95-14C (Mean Dose, 4.2 mgag)
a -Tissue
1 b
ug/9
Liver
17.17
Plasma
2.37
Kidney
1.05
Lung
0.98
Spleen
0.48
Bone Marrow
0.41
Red Blood Cells 0.43
Adrenals
0.44
Testes
0.33
Skin
0.38
Muscle
0.41
Subcutaneous Fat
0.15
Eye
0.18
2 lig/g
21.46 2.17 0.89 0.90 0.50 0.43 0.59 0.42 0.33 0.38 0.31 0.28
0.15
Rat Number
3
4
iig/g
pgzi
21.22 2.37 1.10 1.03 0.51 0.39 0.58 0.49 0.35 0.35 0.31 0.19
0.16
22.25 2.27 1.20 1.31 0.57 0.79 0.37 0.32 0.41 0.32 0.29 0.27
0.18
5 pg/g--
18.99 2.05 1.10 1.10 0.48 0.35 0.37 0.35 0.35 0.34 0.26 0.13
0.13
6 pg/-g
22.27 2.05 1.22 1.03 0.49 0.38 0.34 0.41 0.37 0.32 0.18 0.15
0.16
Mean lig/g
20.56 2.21 1.09 1.06 0.51 0.46 0.45 0.41 0.36 0.35 0.29 0.20
0.16
Brain and abdominal fat were also assayed but level of carbon-14 was too low to quantitate (< 0.08 pg/g) in abdominal fat, and too low to detect in brain (< 0.05 jig/g).
b
14
Total carbon-14 concentration is expressed as ug equivalents of FC-95- C/g.
LO-
Table 4
Percent of Dose Present in Tissues at 89 Days after a Single Intravenous Dose of FC-95-14C (mean Dose, 4.2 mg/@kg)
Tissue
Liver a Plasmat Red Blood
ceiiscKidney2@ Lung a Testes@t
a Spleen
1 %
20.16 -2.81
0.42
0.27 0.15 0.10 0.02
2 %
27.11 2.82 0.64
0.22 0.11 0.09 0.02
Rat Number
3
4
t
%
25.39 2.84 0.58
29.06 3.00 0.41
0.24 0.12 0.11 0.02
0.30 0.17 0.12 0.03
5 %
24.96 2.75 0.41
0.27 0.13 0.10 0.02
6 %
24.58 2.64 0.37
0.30 0.11 0.10 0.02
2@ Data is expressed as percent of dose present in whole organ.
b Data is estimate of percent of dose present in plasma. Plasma volume = 31.3 ml/kg body weight (4 ).
Data is estimate of percent of dose present in red blood cells. Red blood cells = 26.3 ml/kg body weight (4
Mean %
25.21 2.81 0.47
0.27 0.13 0.10 0.02
35.
30,
14
25
44 0
41 20
14
41 10
10
5
0 0
Figure I
Cumulative Excretion of Total Carbon-14 in Urine 14
after a Single IV Dose of FC-95- c (Mean Dose, 4.2 mgag) Mean of 6 Rats
io
io
io
@o
;o
6;
7;
DaYs Post Dose
Figure 2
Cumulative Excretion of Total Carbon-14 in Feces after a Single IV Dose of FC-95- 14 (Mean Dose, 4.2 mg/kg) Mean of 6 Rats
u 0
020-
0,15 9 .ri
4) 010
5.
ol 0
12.6 1 1.2
10
20
30
4;
50
60
70
Days Post Dose
Appendix 1 Determination of Carbon-14 Content of Dosing Solution Just prior to dosing of rats, the PC-95- 14 C dosing solution was sampled with calibrated micropipettorsk directly into counting vials. Six 10 ul and six 50 ul aliquots were pipetted, 1 ml of water and 15 ml of Aquasol(b were added@-, corrections were made for background and counting efficiency and, using the specific activity of FC-95-14C already deterinine4ir@t,he uCi/2.0 al was calculated. The data are shown in Appendix Table 1. The dose administered each rat is 2.0 ml of solution containing 0.553 UCi of pC-95-14C which is 1.21 mg of FC-95-14C. This is a mean dose of 4.2 mg/kg.
L/I Micropipettor, Lab Industries, Berkeley, California. Aquasol(D was found to be a suitable solvent-scintillent for FC-95-14C during specific activity determination (1). Specific activity = 0.459 uCi/mg. Specific activity determination has been reported (1).
-14-
Appendix Table I Carbon-14 Content of Dosing Solution
IO.UL Aliquot uci/2.0 mi
50.)j)-Aliquot pCi/2.0 ml
0.5602 0.5554 0.5614 0.5628 0.5612 0.5554 Overall average
0.5526
0.5624 0.5532 0 5290 0.5390 0.5382 0.5534
0.553
1.21 mg
FC-95-
14 C/2.0
mi
O.V5T6 pCi4mgm
... ....
Appendix 2
Recovery of Total Carbon-14 from Blank
Biological Samples Spiked with FC-95-)4c
The good recovery of total carbon-14 from combusted FC-807-14Cin biological samples has been re orted. (3) Since the carbon label is cL to the sulfur
atom in both FC-95-14C and the components of FC-807-14C, it is reasonable
to expect that good recovery of total carbon-14 from FC-95-14Cand/or its
metabolites in biological samples can be attained. For each set of s!mples combusted, four replicates of 10 pi, 50 ul, and 100 ul of diluted F -95-14C dosing solution were aliquoted with calibrated micropipettors directly into scintillation vials. At the same time using the same
solution and pipettes, either three or four replicates of 10 ul, 50 P)
and 100 ul we're aliquoted directly into combustion cones which already contained blank biological material (fecal, liver, muscle, or spleen homogenates). The combustion cones were dried and then pelletized with
5 cm ash)ess filter paper. Blank filter paper pellets were c mbusted
and the solvents collected in the vials to which the FC-95-I&IC
had been added directly. One each of the 10 ul, 50 ut, and 100 ul FC-95- 14C
spiked pellets were routinely combusted at the beginning, middle, and end of each set of biological samples. After correction for background and counting efficiency, percent recovery was calculated by comparing mean results from direct addition and combustion. The mean recovery data for three sets of fecal samples that were analyzed on different days for total carbon-14 (FC-95-i4C) are shown in Appendix Table 2. The mean recovery is 98.0 1.5%. Since each entry in the table is
the mean of four determinations, this mean recovery is based on 36
determinations. Recovery of total carbon-14 from spiked tissue homogenates (not sh@wn) was also 98%. Thus, good recovery of total carbon-14 from FC-95-1 C spiked biological material is shown.
Appendix Table 2
Recovery of Total Carbon-14 from Blank Fecal Homogenate Samples Spiked with FC-95-14C
10 -)IIA
50 ul
loo iii
97.,4b-'-E 100.6 97.9 98.6
99.5 97.0 95.4 97.3
97.7' 98--1 98.1 98-o
Overall average 98.0 1.5% (mean S.D.)
Amount
of
FC-95-
14 C
reference solution added.
b Data are expressed as % recovery dpm from combustion dpm from direct addition x loo)
Each entry is the mean of 4 combustion recovery determinations.
-17-
Appendix 3
Comparison of darbon-14 Analysis of Urine Samples by Oxidation Versus Direct Counting in Aquasol4D
The urine carbon-14 excretion data reported in this report are based on direct counting in Aquasol(ID.However, there is a concern that an insoluble metabolite or complex might exist in the urine so that not all of the radioactivity in the urine is counted. To investigate this possibility, concentration data from combustion were compared to concentration data obtained from direct counting of the same urine samples. The data are shown in Appendix Table 3. The mean ratio of the results from the comparison is 0.97. Thus, direct counting in AquasolOb is a valid method to assay total carbon-14 in the urine samples.
APPwidix Table 3
CompaLrison of Carbon-14 Analysis of Urine Samples by Oxidation versus Direct Counting in AquasolO
Sample Number
1 2 3 4 5 6
Direct Counting
0.98 1.04 0.76 0.66 0.86 0.77
Oxidized (JAg/g)k
0.95 1.01 0.75 0.62 0.72 0.84
Mean
Ratio Oxidized/ Direct Counting
0.97 0.97 0.99 0.94 0.84 1.09
0.97
Data expressed as pg FC-95-14 C equivalents/ml. Data expressed as pg FC-95- 14 C equivalents/g.
Distribution List
M.T. Case S.F. Chang G.J. Conard H.E. Freier E-n -nr;fglt-h L.I. Harrison T.L. Kerley J.D. LaZerte L.J. Magill R.A. Nelson R.E. Ober J.A. Pendergrass R.A. Prokop A.L. Rosenthal F.A. Ube] P. Venkateswarlu DMG Central File Tech Communications Central Files
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