A validation study comparing accelerator MS and liquid scintillation counting for analysis of C-14-labelled drugs in plasma, urine and faecal extracts

A comparison has been made between accelerator mass spectrometry (AMS) anal ysis and liquid scintillation counting (LSC) of plasma, urine and faecal sa mples containing C-14-labelled drugs. In an in vitro study in which human p lasma was spiked (the term spiked is used in Section 2.6) with C-14-Flucona zole (C-14-FL) over a concentration range of 0.1-2.5 dpm/ml, a correlation coefficient of 0.999 was determined for AMS analysis versus extrapolated LS C data. No significant day to day (or inter-day)variation was seen (P < 0.0 5 by ANOVA). Coefficients of variation for these analyses ranged from 2.68 to 6.50%. In vivo studies in which rats were given a high (11.5 <mu>Ci/kg) or low (18.1 nCi/kg) radioactive dose (to model an exposure of 0.9 mu Sieve rt to man) of C-14-Fluticasone propionate(C-14-FP) showed that there was al so a good correspondence between AMS and LSC data. A mass balance study in a single rat given the 0.9 mu Sievert human modelling dose of C-14-FP demon strated that over 80% of the dose was excreted in the faeces by 96 h; less than 1% of the administered dose was excreted in the urine. The limit of re liable measurement of drug related material, above background concentration s, by AMS analysis in this study was approximately 0.1 dpm/ml for plasma, 0 .01 dpm/ml for urine without any sample extraction or concentration and 0.0 1 dpm/ml for faecal extracts. The data reported here demonstrate that AMS i s an ultrasensitive and reliable method for analysing C-14-labelled drugs i n human and animal body fluids. (C) 2000 Elsevier Science B.V. All rights r eserved.