DETERMINATION OF PLASMA MEXILETINE LEVELS WITH GAS-CHROMATOGRAPHY MASS-SPECTROMETRY AND SELECTED-ION MONITORING

Mexiletine, 1-(2,6-dimethylphenoxy)-2-aminopropane (Mexitil), is an or ally effective agent useful in the treatment of serious ventricular ar rhythmias. This paper describes a gas chromatographic-mass spectrophot ometric assay with selected-ion monitoring for the measurement of plas ma or serum mexiletine levels. The drug and internal standard (p-chlor ophenylalanine methyl ester) were extracted from plasma into ethyl ace tate-hexane-methanol (60:40:1, v/v). After separation and evaporation of the organic phase, the drug and internal standard were derivatized to their pentafluoropropyl derivatives prior to analysis. The reproduc ibility of the daily standard curve yielded mean inter- and intra-day coefficients of variability from 0.7 to 11.0%. The coefficients of var iability for control plasma samples (0.5 and 1.0 mu g/ml) ranged from 2.6 to 5.0% and the accuracy of the assay was 106 +/- 6 and 100 +/- 5% for the low and high level controls respectively. The limit of quanti tation for the assay was 0.1 mu g/ml. No interfering peaks were detect ed in any patient samples. This method can be used as a primary analyt ical method to measure mexiletine plasma levels or can serve as a conv enient back-up method to HPLC procedures when contaminating peaks coel ute with mexiletine.