Simultaneous spectrophotometric determination of glutethimide and barbiturates.

T HE POSSIBILITY OF DRUG intoxication frequently arises in patients admitted to the hospital in coma. Ingestion of salicylates by children and of barbiturates by adults are the most common causes. Since the introduction of glutethimide (2-ethyl-2-phenylglutarimide) in 1954, there have been increasing reports implicating this drug in drug intoxication. Since the clinical picture of glutethimide intoxication is indistinguishable from that of barbiturates, diagnosis must be confirmed by identifying the drug in blood samples. Well-established ultraviolet spectrophotometric methods are available for identification of these substances (1, 2). Each of these procedures requires about 2 h for completion. Because the laboratory is often asked to look for both barbiturates and glutethimide, it seemed desirable to combine the analytical procedures. Measurement of glutethimide is based on its characteristic absorption peak at 233 nm in a strongly alkaline solution and its progressive timed hydrolysis. The change in optical density in a given time interval is proportional to its concentration. The method for barbiturates is based upon the observation that these substances have the absorption spectrum of one resonance form at pH 13 and the absorption spectrum of a diferent resonance form at pH 9.5. The difference in optical density of the solution at pH 13 at 240 and at 260 nm, when the solution at pH 9.5 is used to set the instrument, is directly proportional to the concentration.