A single liquid-chromatographic procedure for therapeutic monitoring of theophylline, acetaminophen, or ethosuximide.

Simultaneous and semi-automated determinations of theophylline, acetaminophen, and ethosuximide from human serum are possible through use of a programmable autoinjector, an isocratic mobile phase, and reversed-phase "high-performance" liquid chromatography on a muBondapak C18 column. To avoid salt damage to the valves and the fittings of the autoinjector and solvent pump, we used only volatile, ion-pairing buffers such as triethylamine/acetic acid or N-ethylmorpholine/acetic acid at apparent pH 4.8 in acetonitrile/water (1/11 by vol). With this method we can separate theophylline, acetaminophen, and ethosuximide from 26 other drugs, metabolites, and related substances. Results by this procedure and the EMIT procedure for theophylline and ethosuximide in patient and control sera correlated well (r = 0.944 and 0.968, respectively). We conclude that this single chromatographic system reliably and economically yields analysis of three widely used therapeutic drugs on a routine or emergency basis.