Tr. Browne et al., PERFORMANCE OF HUMAN MASS-BALANCE STUDIES WITH STABLE ISOTOPE-LABELEDDRUG AND CONTINUOUS-FLOW ISOTOPE RATIO MASS-SPECTROMETRY - A PROGRESSREPORT, Journal of clinical pharmacology, 38(4), 1998, pp. 309-314
We propose performing human mass balance studies by administering stab
le isotope labeled (C-13 or N-15) drug and quantitating excess (above
background) C-13 or N-15 in urine, serum, and feces by continuous flow
-isotope ratio mass spectrometry (CF-IRMS). Theoretical calculations a
nd empirical data (dynamic range, linearity, sensitivity, precision, a
ccuracy) are presented to establish that commercially available CF-IRM
S instruments can quantitate stable isotope labeled (one or two N-15 o
r C-13 labels) drug concentrations of 1.0 mu g/mL or greater in urine,
serum (N-15), or feces. More than two C-13 labels may be necessary to
quantitate 1.0 mu g/mL of drug in serum. Three volunteers received 65
0 mg of (NC2)-N-15-C-13- acetaminophen, and urine was collected for 72
hours. Percent of administered label recovered in urine from the thre
e subjects was 97.4, 78.9, and 95.4 for C-13 and 90.3, 77.0, and 90.6
for N-15. Fecal recovery of label for one subject was 0.9% (C-13(2)) a
nd 1.1% (N-15). Serum pharmacokinetic values obtain ed by counting C-1
3 or N-15 in one subject were as expected for acetaminophen. This meth
od appears to be promising, and further validation is ongoing. (C)1998
The American College of Clinical Pharmacology.