title: 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.
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.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas-Houston Health Science Center, 77030, USA.
authors.forename: A
authors.initials: A
authors.lastname: Dasgupta
authors.forename: P
authors.initials: P
authors.lastname: Appenzeller
authors.forename: J
authors.initials: J
authors.lastname: Moore
mesh_terms: D000889:Anti-Arrhythmia Agents / Q000097:blood* / Q000737:chemistry*; D002849:Chromatography, Gas / Q000379:methods*; D016903:Drug Monitoring / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D008801:Mexiletine / Q000097:blood* / Q000737:chemistry*; D010705:Phosgene / Q000031:analogs & derivatives* / Q000737:chemistry; D012680:Sensitivity and Specificity
chemical_list: D000889:Anti-Arrhythmia Agents; D010705:Phosgene; C012586:trichloroethyl chloroformate; D008801:Mexiletine