HPLC investigation of free and bound propofol in human plasma and cerebrospinal fluid.

The paper compares the total propofol concentration in the cerebrospinal fluid (CSF) with the free drug concentration in plasma measured in 35 humans scheduled for elective neurosurgical procedures during propofol anaesthesia. The concentrations of total and free propofol in the blood and CSF samples were measured by means of HPLC using liquid-liquid extraction and ultrafiltration in the sample preparation procedure. The arterial blood and CSF samples (collected from intraventricular drainage) were taken at the same time. According to the obtained results, the usually expected equality between free drug concentration in plasma and its total concentration in CSF is not valid for propofol: the unbound propofol concentration in plasma is not equal to its total concentration in CSF (p < 0.05). This difference suggests a substantial contribution of active transport in propofol transfer from blood into CSF. Moreover, the paper shows the presence of bound propofol in CSF, which is a novel finding. Copyright 2003 John Wiley & Sons, Ltd.