Barbiturates are a class of compounds that are central nervous system depressants. Extended administration or abuse of barbiturates can lead to physical and psychological dependence. Although tolerance to the intoxicating effects of barbiturates may increase with use, there is very little increase in tolerance to the toxic side effects of high doses. As a result, the therapeutic index for barbiturates is lower than for other sedative/hypnotic drugs such as the benzodiazepines. The barbiturates also have an additive effect when administered with other central nervous system depressants. Barbiturates can be analyzed in either their underivatized or derivatized forms by gas chromatography. Derivatization of the barbiturates is most commonly performed by methylation of the amido nitrogens in positions 1 and 3. Methylating reagents like tetramethylammonium hydroxide and trimethylanilinium hydroxide can be used for on- column derivatization of the barbiturates. Analysis of barbiturates can also be performed on underivatized compounds; however, underivatized barbiturates have a tendency to produce overloaded or tailing peaks. 2 figures