Microdosing has been used as an investigative pharmacokinetic tool for approximately 10 years. Initial skepticism of the value of these studies was followed by investigative clinical trials to understand the circumstances when they provide useful data and this has led to routine use. When first introduced, accelerator mass spectrometry coupled with LC fractionation (LC+AMS) was the only technology that could provide the sensitivity required for these studies. Over the years, LC-MS/MS sensitivity has improved so that it is now viable to use this technique for microdosing studies, and a decision needs to be made on what technique to use.

Traditionally, absolute bioavailability ( has been determined using a crossover study design, requiring administration of an IV dose expected to give plasma concentrations similar to those arising from the therapeutic extravascular (EV) dose. An alternative approach is to administer an isotopically labelled IV microtracer dose concomitantly with the EV dose (see Figure 1 This methodology is both scientifically superior and more resource efficient With the inclusion of ABA data mandatory for marketing applications submitted to the Australian TGA 1 and other regulators increasingly asking for this information, a growing number of such studies are being conducted

Arachidonic acid metabolites are biologically active lipid molecules that regulate many functions and play critical roles in a variety of physiological and pathophysiological processes. Some of the eicosanoids are used as a potential biomarkers related to inflammation, immune reactions and side-effects of drugs. Eicosanoids are derived from arachidonic acid and then from other metabolites by enzymatic and non-enzymatic reactions and have very similar structure and physical properties. Pattern of intermediates and final eicosanoids production is determined in a stimulus and cell-specific fashion. Fast and simultaneous qualitative and quantitative profiling of eicosanoids (lipidomics) in biological samples is possible because of high sensitivity and selectivity of liquid chromatography/mass spectrometry methods and simplicity of sample preparation.

5-Fluorouracil (5-FU) is well-known anti-cancer drug,widely used for decades against a variety of solid tumors. 5 -Fluorouracil has a narrow therapeutic index, there is a very little difference between the theoretical minimum effective dose and the maximum tolerated dose, and therefore it needs to be administrated intravenously to control therapeutic dosage.

The 6th Global CRO Council for Bioanalysis (GCC) Closed Forum was held on 27 March 2012 in San Antonio, TX, USA, the day before the start of the 6th Workshop on Recent Issues in Bioanalysis.

The importance of appropriate sample management in regulated bioanalysis is undeniable for clinical and non-clinical study support due to the fact that if the samples are compromised at any stage prior to analysis, the study results may be affected. Health authority regulations do not contain specific guidance on sample management; therefore, as part of the Global Bioanalysis Consortium (GBC), the A5 team was established to discuss sample management requirements and to put forward recommendations.