Application of the dried spot sampling technique for rat cerebrospinal fluid sample collection and analysis

Dried blood spotting (DBS) sample collection is gaining favor in the pharmaceutical industry due to benefits that include reduced animal usage and easier sample shipment and storage when compared to traditional plasma collection/analysis. The applicability of the DBS card to alternate, limited-volume, matrices has not been as fully characterized as their use with whole blood. In this paper we explored the application of the DBS sample collection technique to rat cerebrospinal fluid (CSF). A reverse phase HPLC–MS/MS method was developed and characterized for the quantitative bioanalysis of the α7 neutonal nicotinic acetylcholine receptor agonist PHA-00543613 in CSF using the dried spot sampling technique. The characterized assay and dried spot sampling technique was employed to analyze serially collected in vivo rat CSF samples after a single 4 mg/kg dose of PHA-00543613 in CSF-cannulated rats. The DBS strategy enabled the collection of more timepoints and produced comparable exposure results to those obtained by the collection and analysis of liquid CSF samples but notably with eight less animals.