Highly sensitive method for the quantitation of homovanillic acid in cerebrospinal fluid

Homovanillic acid in minute samples (50-100 microliters) of cerebrospinal fluid can be quantitated as its O-dimethylthiophosphinate methyl ester. The derivative is determined after glass capillary gas chromatography (GC) with high sensitivity by using a phosphorus-specific thermionic detector or by mass fragmentography, combined with a large sample volume split-splitless injector. The dimethylthiophosphinic esters show excellent stability against moisture and air. The precision of the overall procedure is 5.4% (GC) and 3.8% (GC-mass spectrometry). The method shows good linearity (r = 0.9999) over three orders of magnitude, from 500 pg to 500 ng. The lowest detectable concentration of homovanillic acid is 2-5 ng/ml. Concentrations of homovanillic acid determined in cerebrospinal fluid were 9.9-63.1 ng/ml (n = 10, mean = 30.9 ng/ml).