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rac.labelling of molecures
offers significant advantages compared to 3H rabeled
molecules including, (a) Stability in biological fluids (3H is
ta-olte and possibility
*:li:|. yirt biological water (b) Longer hatf-tife and better counting
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detectabltrty, (c) Lower radio toxicity and (d) From a synthetic
standpoint,
labeling offers greater selectivity, apart from greater ease
of handring and
lia
storage stability.
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euttingEdge
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Fig 3: Rodio-TLC ond lmoging sconner (A), Schemotic diogram of chromatogram (B)
compound (s) seporation initial spotting-i, compound-ii and iii
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TLC plote
of C, with radiolabeted
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Tritium (3H/f)
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chromotogram
obtoined from online uV ond rodiodctive detectors (P.-RAM)
connected with HPLC
Nal
radiolabeled
compounds requires dedicated instruments. Structural
elucidation of the labeled compounds can be carried
out using dedicated instruments such as NMR, IR, UV
Radiochemical purity
and 40-45%o
for
3H.
is
Spinco Biotech
CuttingEdge
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April 2014
RAM Radio-TLC)' In
this
iiquid
generated
UV/ELSD
unique
often
methods
LCIMS/MS
and
applications. LC/MS
identification
structural
for
yieta amUiguous data
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practice100o/orecoveryistechnica11ynotfeasib1eand
the current accepted recovery ranges from 85-900/o'7'8
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and 61-105%
(humans)'
Drug metabolism
studres
:
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of
toxicity.
Whole Body
AutoradiograPhY
freeze-dried,
(pharmacokinetics),
April 2014
in the
excreta (urine,
faeces
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data
andtimetoacquirethedata.Deve1opmentofsensitive
detectors like phosphorimagers to replace X-Ray fllms'
ability to produce the images of distribution/deposition
of radioactivity in various parts of the body so that it
to get radiographic
Applications
film
compound
tumour and Blood Brain Barrier (BBB) penetrattons'
This technique requires more radioactive compound
models.
e-Fate
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studies
CuttingEdge
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ir# microo'osing, in iitico', n-iirZ
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to
used as tracers.
Microdosing
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for early
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in2013.
Spinco Biotech
conduct
its
release into the environment, either from an intended use
or an accidental release, before registration. This study
referred to as 'Environmental fate' studies, includes
studies
CuttingEdge
Conclusion
Radiolabeled molecules or their metabolites are 'GOLD
STANDARDS' to establish pharmacokinetics, ADME.
toxicity and environmental (soil and water) fate studies.
Microdosing of radiolabeled drugs also now offers the
prospect of the oppornrnity of working directly into
References
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3.
4.
5.
6.
7.
8.
9.
RoA foges, J. Richdrd Heys, Thomu Moenius, Preparation oJ Compounds Labeled with
Trliuil aild Cdrbon-ll, Wilql (2009)
SfiniyasG,UnnyVK,MukkantiK,ChoudatyBM,ApptRadiatlsot.20t3,.Z2:145-51
M. F Bdrakd. A. N. Farag, M. T. Ragab, M. M. El-Fouly & F K. Et-Baz , Isotopes in
Lnv;ronnental aal Health Stddi,,. I 9q0. - | 2q. 3 I t - 3 I R. Swanson d O. Hoegh-Guldberg, Marine Biolog), 1998, 131, 83 93; J. T. Wang, A. E.
Dougld, Marine Biolag, 1999, 135,2, 219-222
Ctdbtree,R.H.(1979)."lridiumcompoundsincatab)sis".Acc.Cheil.Resj2(g):331-337,
J. Ory. Chem. 1936,51 (14):2655 2661.
Beryman, R. G., J. Amd. Chm. Soc., 2A02, 124(t0),2092.
Beunea J. H., Beilhen,.I- H., S.hellens, J. H. M. Mass baldnce studies, with a focus on
anticancer drugs. Clin. Pharnacokiilel2006, 15.33 58
Suwel, M., C.G. Sahajwalla, Netr Drug Development, Regulatary paradigils Jbr Ctinicat
Pharamcology and Biopharmaceutics. New York: Marcel Decke4 2004, pp. 1A7-2j2
Sarah J. RolJLy, R. Scott Obach, Jenny 1- Gedge, and Dennis A. Smith, Dlug Metabolism
11. Guidance _for lndust!, Inrestigdtors, dnd Reviewers. Etploratary IND Stodies. FDA,
CDER, Jantnry 20a6
ETA
April20L4