Evaluation of adsorption of various analytes in cerebrospinal fluid

Abstract

For drug development, especially for research on the central nervous system (CNS), it is necessary to measure the concentration of compounds in cerebrospinal fluid (CSF), next to the common body fluids such as plasma and urine. In urine and CSF the quantification of compounds is difficult because the risk of adsorption to sampling materials. For urine, additives can be used to avoid this. However, for CSF sampling this is not allowed because of patient safety reasons. In addition, the concentration in CSF is low, which makes detection and quantification extra difficult. In this investigation, the impact of various materials on adsorption of the compounds during sampling and storage of CSF was evaluated and the adsorption is compared to the physiochemical properties (log P and pKa) of the compounds. This might help predicting adsorption based on the properties of the compounds. Also, the possibility to set up a generic procedure with useful materials for which the total adsorption is less than 15% was evaluated. For this purpose six compounds were selected based on their log P and pKa. These were tested for adsorption on the materials that are used for CSF sampling in various phase-I clinics. From the results it was concluded that the choice of materials really can help to limit adsorption. However, the impact is not large enough to completely avoid adsorption for all compounds. It was also clear that log P is not the only physicochemical parameter to predict adsorption.