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

Abstract

A comparison has been made between accelerator mass spectrometry (AMS) analysis and liquid scintillation counting (LSC) of plasma, urine and faecal samples containing ¹⁴C-labelled drugs. In an in vitro study in which human plasma was spiked (the term spiked is used in Section 2.6) with ¹⁴C-Fluconazole (¹⁴C-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 LSC data. No significant day to day (or inter-day)variation was seen (P14C-Fluticasone propionate(¹⁴C-FP) showed that there was also a good correspondence between AMS and LSC data. A mass balance study in a single rat given the 0.9 μSievert human modelling dose of ¹⁴C-FP demonstrated 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 reliable measurement of drug related material, above background concentrations, 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 0.01 dpm/ml for faecal extracts. The data reported here demonstrate that AMS is an ultrasensitive and reliable method for analysing ¹⁴C-labelled drugs in human and animal body fluids.