| Summary: Abstract: A technique has emerged in the past few years that has enabled a drug’s intravenous pharmacokinetics to be readily obtained in humans without having to conduct extensive toxicology studies by this route of administration or expend protracted efforts in formulation. The technique involves the intravenous administration of a low dose of 14C-labelled drug (termed a tracer dose) concomitantly with a non-labelled extravascular dose given at therapeutic levels. Plasma samples collected over time are analysed to determine the total parent drug concentrations by LC-MS (which essentially measures that arising from the oral dose) and by LC followed by accelerator mass spectrometry (AMS) to determine the 14C-drug concentration (i.e., that arising from the intravenous dose). There are currently no published accounts of how the principles of bioanalytical validation might be applied to intravenous studies using AMS as an analytical technique. The authors describe the primary elements of AMS when used with LC separation and how this off-line technique differs from LC-MS. They then discuss how the principles of bioanalytical validation might be applied to determine selectivity, accuracy, precision and stability of method involving LC followed by AMS analysis. |
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| Published Date: | 23 Feb 2011 |
| Author | Graham Lappin, Mark Seymour, Graeme Young, David Higton, Howard M Hill |
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