A modified gas-liquid chromatographic assay to monitor plasma mexiletine in a tinnitus study.

In a clinical study of betahistidine, diazepam and mexiletine for the oral chemotherapy of tinnitus, the hospital Pharmacy was requested to devise a double-blind triple cross-over trial including a placebo. As mexiletine is a potent cardiovascular drug and also as a measure of compliance, a rapid and sensitive gas-liquid chromatographic (GLC) method was developed to monitor its plasma concentration in patients who took part in the trial. This assay involved a preliminary ethereal extraction of the drug and internal marker (3-N,N-diethyl carbamyloxy pyridine) in a 1 ml plasma or urine sample under alkaline condition. The concentrated extract was redissolved in distilled methanol (10 microliters) and an aliquot (2 microliters) was analysed by a GLC system (3% OV17 on Gas Chrome Q, 10-100 mesh) linked to a nitrogen sensitive detector. The calibration graphs relating peak height ratios of the drug to the internal marker and concentration were linear and reproducible over the ranges of 5.0 to 100.0 ng/ml and 1.0 to 10.0 micrograms/ml for both plasma and, or urine samples. The steady-state plasma concentrations of mexiletine in 5 patients, from whom blood samples were obtained as a measure of compliance, ranged between 570 to 1911 ng/ml which were similar to those reported from treatment of ventricular arrhythmias with similar dosage regimen of 200 mg mexiletine hydrochloride three times per day.