Therapeutic Drug Monitoring 1998-06-01

Gas chromatography-electron ionization and chemical ionization mass spectrometric analysis of serum mexiletine concentration after derivatization with 2,2,2-trichloroethyl chloroformate: a novel derivative.

A Dasgupta, P Appenzeller, J Moore

Index: Ther. Drug Monit. 20(3) , 313-8, (1998)

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Abstract

Mexiletine (Mexitil) is an antiarrhythmic agent used in the treatment of ventricular arrhythmia. The drug has a narrow therapeutic window, and monitoring its serum concentration is recommended. The authors describe a gas chromatography-mass spectrometric (GC/MS) assay of mexiletine using selected ion monitoring. Mexiletine was extracted from alkaline serum with dichloromethane followed by derivatization with 2,2,2-trichloroethyl chloroformate. The reaction was completed in 30 minutes at 70 degrees C. N-propylamphetamine was used as the internal standard. The ions monitored were m/z 58, 102, 122, 232, and 234 for derivatized mexiletine and m/z 56, 91, 131, 260, and 262 for the derivatized internal standard. The within-run precision at a serum mexiletine concentration of 1 mg/l was 1.7% (mean = 0.981, SD = 0.017 mg/l, n = 8) and the between-run precision was 3.3% (mean = 0.983, SD = 0.033 mg/l, n = 6). The assay was linear for serum mexiletine concentrations of 0.2 to 2.5 mg/l. The detection limit was 0.1 mg/l. The authors observed no carry-over problem in their assay. They observed a good correlation between mexiletine concentrations measured by a reference laboratory (Associated Regional University Pathologists, Salt Lake City, UT, U.S.A.) and by the new GC/MS assay.