A SENSITIVE GAS CHROMATOGRAPH ASSAY FOR THIOPENTONE IN PLASMA

A sensitive flame ionization gas chromatograph assay method has been developed for thiopentone in human plasma. The extraction procedure minimizes desulphuration of the drug while removing most endogenous substances and is limited by a maximum of 50 ng ml"1 in 2-ml plasma samples. There is linearity throughout the 30.0-5.0 (xg ml"1 and 5.0-0.1 ng ml"1 ranges. Extraction of six replicate 2.5-(ig ml"1 samples resulted in a coefficient of variation of 3.0%. Similar treatment of six 0.20-[ig ml"1 samples afforded a coefficient of variation of 4.6%. Thiopentone in biological fluids has been assayed most recently using spectrophotofluorimetry and a number of gas chromatograph methods. A recent pharmacokinetic study required the development of a flame ionization technique which would exhibit a sensitivity greater than that reported by Braddock and Marec (1965), yet circumvent the need for methylation as suggested by Becker (1976). It was important also that such an approach exhibit a wide range of linearity, similar to that reported by Dayton and others (1967). This communication describes an extraction procedure, coupled with a gas chromatograph analysis using a flame ionization detector, which permits determination of plasma concentrations of thiopentone in the 30.0-0.1;xg ml"1 range, with a low-end sensitivity of less than 25 ng ml"1