Determination of morphine in cerebrospinal fluid and plasma by high-performance liquid chromatography with electrochemical detection.

Two methods for the extraction of morphine from cerebrospinal fluid or plasma with quantitation by high-performance liquid chromatography with electrochemical detection were compared for accuracy, precision and ease of preparation. One procedure was a standard extraction procedure and the other utilized a commercially available liquid-liquid extraction column. Both methods produced linear calibration curves over the concentration range of 1-200 ng/ml with coefficients of correlation of 0.999. Since the electrochemical detector is capable of detecting 20 pg of morphine, biological samples as small as 0.1 to 0.4 ml can be quantified with an average relative precision of 4.1 +/- 3.9% over the concentration range 1-200 ng/ml. The potential clinical importance of the assay is demonstrated using a time course distribution study of morphine in the cerbrospinal fluid and plasma of a Rhesus monkey.