Accelerator mass spectrometry (AMS) is being used more widely to provide PK data for early decision making or to generate absolute bioavailability data in later phases of development. Presently, there is no clear consensus on the level of the scientific validation required for these assays. The European Bioanalysis Forum (EBF) has conducted two surveys with its members and presented the results at its 4th Open Symposium. With AMS being used for discrete scientific assessment, method establishment of AMS assays should focus on science rather than trying to fit the assay parameters into validation criteria used for Regulated Bioanalysis guidance, and an amount of freedom of execution and interpretation is needed. Hence, the EBF focuses their recommendation on introducing terminology around scientific qualification or validation to be used in relation to AMS. Guidance is given on which parameters should be investigated when a qualified method is required. The recommendations of the EBF for scientific validation are described herein. The scientific validation of AMS assays will be different to that applied for LC-MS/MS assays, and an example is that accuracy and precision limits, as used for ligand-binding assays, would be more appropriate.

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The absorption and disposition of roquinimex (Linomide) were studied in four male and two female healthy volunteers. The subjects received a single oral aqueous solution of 14C-labelled roquinimex, about 0.1 mg/kg, after an overnight fast. Blood samples were taken and urine and faeces were collected for 10 days after dosing. The plasma, urine and faeces concentrations of roquinimex and metabolites were determined by high-performance liquid chromatography (HPLC) with radiochemical detection. The metabolites were identified by HPLC-mass spectroscopy (MS). The plasma concentration-time profiles of roquinimex exhibited a rapid absorption followed by a bi-exponential disposition. A secondary peak was observed between 6 and 8 h, indicating enterohepatic circulation (EHC) of roquinimex. The terminal disposition half-life was estimated as 27 h. The primary metabolic pathways of roquinimex were hydroxylation, demethylation and conjugation. The major compound in plasma was roquinimex; metabolites were only occasionally detected. In urine and faeces, roquinimex accounted for 2% of the dose and conjugated and hydroxylated metabolites each accounted for about 30% of the dose. A model was derived for the plasma concentrations of roquinimex and the amount of urinary excreted roquinimex to take into account EHC. This model improved the goodness-of-fit according to common goodness-of-fit criteria. The values of the pharmacokinetic parameters were similar using compartmental and non-compartmental methods, indicating that the contribution of EHC of roquinimex is of minor importance in the evaluation of the pharmacokinetics of roquinimex.

Bioanalysis Zone carried out a survey to evaluate the use of and attitudes to DBS analysis among our readership in the bioanalytical community. DBS analysis has generated a huge amount of interest in recent years. We wanted to take a snapshot of the field and determine whether a consensus is emerging on the future of DBS. We asked you for your honest opinions and you delivered! You can view the full results at www.bioanalysis-zone.com. We have a selection of short opinion articles below, giving a range of viewpoints on the current and future use of DBS, alongside some of the survey results.

The method described here is suitable for bioanalysis of tasquinimod in whole blood from humans in clinical studies.

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