Three alkylation methods for the determination of indometacin in plasma by electron capture gas chromatography.

The following alkylation methods for the determination of indometacin in plasma by electron capture gas chromatography are compared: 1, alkylation with diazopropane; 2, extractive alkylation; 3, alkylation by a solid-liquid phase transfer catalysed process. The drug in plasma at pH 4.0 is initially extracted with heptane containing 5% n-pentanol. The methyl ester of indometacin is based as internal standard. After alkylation to the propyl ester according to one of the three alkylation methods, indometacin can be determined down to 5 ng per sample by electron capture gas chromatography. The relative standard deviations (n = 10) at the 200 ng level are 5.1% for the alkylation with diazopropane, 7.5% for the extractive alkylation technique and 3.5% for the alkylation by the solid-liquid phase transfer catalysed process. The comparatively low value obtained by the last method indicates that decomposition of indometacin can be avoided under such mild conditions.