Improved HPLC analysis for anticonvulsant drugs employing radial compression columns.
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The chromatographic behavior of six calixarene-bonded stationary phases is reported. Varying analyte selectivities (i.e., for phenols, substituted aromatics, polycyclic aromatic hydrocarbons, barbituric acid derivatives, xanthines) exist as a function of the ring-size of the calix[n]arenes (n=4, 6, 8) and the substitution at the "upper rim" with para-tert.-butyl groups. Although eluents with unusually high proportions of water were used, a comparison with conventional reversed-phase (RP) columns shows a predominantly reversed-phase character with remarkable selectivities of these phases. The influences of several organic solvents on retention variations of solutes are compared for RP-C18, phenyl and calixarene phases.
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A rapid procedure has been devised for analyzing anti-epileptic drugs in serum by chemical ionization mass spectrometry. An internal standard, 5-(p-methylphenyl)-5-phenylhydantoin (MPPH), is added to serum diluted in buffer at pH 12. The mixture is washed with diethyl ether to remove neutral lipids, acidified, extracted with chloroform and the chloroform extract evaporated to dryness. The residue is then dissolved in methanol and an aliquot, corresponding to approximately 2% of the original mixture, is deposited in the glass capillary sample cup of the solid probe inlet of the mass spectrometer. The sample is then volatilized by heat into the ion source of the mass spectrometer, where it reacts with ionized methane reagent gas. As the temperature of the probe is increased, quasimolecular ion peaks of the protonated anticonvulsants appear, rise and fall on the oscilloscope tracing, indicating similar but not identical rates of volatilization. We recorded these peaks photographically by opening the shutter of the oscilloscope camera for the entire heating cycle. The concentrations of the anticonvulsants were estimated from the ratio of the height of the peaks of the drug to that of the internal standard on the photograph. The peak-height ratios were proportional to concentration within, above and below the therapeutic range. Other drugs, including barbiturates, carbamazepine, nicotine and caffeine, were readily identified when present. With one solid probe inlet, an assay could be performed every 2 min.
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In two children treated for hypoglycemia and convulsions with diazoxide and diphenylhydantoin, therapeutic serum diphenylhydantoin levels were not achieved despite doses of diphenylhydantoin of 17 and 29 mg/kg/day, respectively. After diazoxide was discontinued, serum diphenylhydantoin levels were within the therapeutic range in each patient with doses of 6.6 and 10 mg/kg/day, respectively. Serum diphenylhydantoin fell to undetectable levels within four days after experimental reinitiation of diazoxide administration in one patient. Although the mechanism for the effect of diazoxide on serum concentrations of diphenylhydantoin is uncertain, an increased rate of metabolism of diphenylhydantoin is suggested by our findings. Decreased plasma protein binding of diphenylhydantoin, induced by diazoxide, was observed and may play a role.
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The management of a patient with seizures involves proper classification, etiologic evaluation, and administration of appropriate therapy. With proper evaluation and management, control of seizures can be expected in the majority of patients. The physician must realize that an epileptic adolescent has intrinsic anxieties and faces social, educational, and vocational restrictions. Failure to deal with these psychosocial problems may result in a greater handicap to the patient than the seizures themselves.
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