Gas-liquid chromatographic (GLC) analysis of phenobarbital by on-column methylation with trimethylanilinium hydroxide gives rise to a major decomposition product, N-methyl-2-phenylbutyramide, in addition to the methylated barbiturate, N,N′-dimethylphenobarbital. This reaction occurs nearly exclusively in the solution phase in the injection port of the gas chromatograph. A mechanism for the decomposition reaction consistent with the available information is presented. This decomposition is shown to be inhibited by certain solvents and this effect forms the basis of a new analytical technique for the simultaneous GLC analysis of phenobarbital, primidone, and diphenylhydantoin.