Analytical validation of accelerator mass spectrometry for pharmaceutical development

The validation parameters for pharmaceutical analyses were examined for the accelerator mass spectrometry measurement of C-14/C ratio, independent of chemical separation procedures. The isotope ratio measurement was specific (owing to the C-14 label), stable across samples storage conditions for at least 1 year, linear over four orders of magnitude with an analytical range from 0.1 Modern to at least 2000 Modern (instrument specific). Furthermore, accuracy was excellent (between 1and 3%), while precision expressed as coefficient of variation was between I and 6% determined primarily by radiocarbon content and the time spent analyzing a sample. Sensitivity, expressed as LOD and LLOQ was 1 and 10 attomoles of C-14, respectively (which can be expressed as compound equivalents) and for a typical small molecule labeled at 10% incorporated with C-14 corresponds to 30 fg equivalents. Accelerator mass spectrometry provides a sensitive, accurate and precise method of measuring drug compounds in biological matrices.