Specific radioactivity determinations of ionic organic compounds of high specific activity by fast atom bombardment and field desorption mass spectrometry

Abstract

Carbon-I4 and tritium labelled ionic organic compounds such as quaternary ammonium salts, steroid sulphates, bile acid conjugates, and oligopeptides have been analyzed for their label distribution and for their specific radioactivity by fast atom bombardment and field desorption mass spectrometry. No significant differences between the quantitative results with both techniques are found. The minimal specific radioactivities detectable by this approach are about 20 MBq mmol-' or 10 GBq mml-' for compounds labelled with one atom of carbon-14 or one atom of tritium per molecule, respectively. Specific radioactivity determinations of highly label led biochemicals are characterized by a precision and an accuracy in the region between 1 % and 5 %.

Radiosynthesis for ADME Studies

“…For high specifi c activity uniformly labeled C -14 aromatic ring products, it may be possible to observe a range of mass spectral peaks from M+ 0 through M + 12 peaks. Comparing the LC -MS results for the radiolabeled API with those of the unlabeled standard can be a useful secondary check of the SA of the high specifi c activity product (Lehmann and Kaspersen, 1984 ;Mayer et al, 2008 ). For low specifi c activity API at single -digit microcurie -per -milligram levels, the results may be very similar to the MS pattern of the unlabeled API and it may be impossible to determine the SA from the MS data.…”

“…Instead, the SA can be measured by comparing the MS of the API with that of the unlabeled standard (Lehmann and Kaspersen, 1984 ;Mayer et al, 2008 ). Alternatively, the SA can be determined by HPLC using a standard curve.…”

Recent Developments in Tritium Incorporation for Radiotracer Studies

“…The use of appropriately labeled CO 2 and hydride in the reduction would allow synthesis of a formyl group multi-labeled with selected isotopes of hydrogen ( 1 H, 2 H, 3 H), carbon ( 11 C, 12 C, 13 C, 14 C) and/or oxygen ( 16 O, 17 O, 18 O). This ability to select isotopes or to label with multiple isotopes will make the reagent even more valuable in a variety of labeling, mechanistic, and NMR studies.…”

“…The recent development of novel stereoand site-selective tritium labeling methodology at high specific activity via a variety of new reagents and techniques has been essential for biochemical research. With the widespread use of high quality analytical tools such as high performance liquid chromatography (HPLC), mass spectrometry [13], and tritium NMR spectroscopy [11] the purity and specificity of the labeled products from these reactions is much more assured than in past years.…”

“…As a further guide to the importance of the radioactive isotopes of hydrogen (tritium, 3 carbon ( 14 C) as biological tracers, it is instructive to conduct a survey of MedLine publications over the period 1964-1999, for the following list of isotopes: 2 H, 3 H, 11 C, 13 C, 14 C, 13 N, 15 N, 16 O, 17 O, 18 O, 18 F, 19 F, 31 P, 32 P, 33 P, and 35 S. More than 200,000 publications are involved in such a survey. Almost 50% of these publications reference tritium, and another 21% involve 14 C, suggesting that almost 70% of published biomedical work involving H, C, N, O, F, P, and S isotopes over the past 36 years has been done with tritium and 14 C.…”