Rapid high-performance liquid chromatographic method for the quantification of mexiletine and its metabolites in serum.

Mexiletine, l-methyl-Z(2,6-xylyloxy)ethylamine hydrochloride (Mexitil@ ), has been shown to suppress markedly ventricular rhythm disorders [l61. Effective serum levels of mexiletine range from ca. 0.5 to 2.0 pg/ml [24,7,8]. Although the antiarrhythmic efficacy of mexiletine is not correlated directly with its serum level [ 3,4,7,8], the determination of the drug is recommended when adverse effects occur, when drug therapy is ineffective in order to differentiate failure of therapy from suboptimal dosing, in patients with cirrhosis of the liver, or in order to check a patient’s compliance. Gas chromatographic (GC ) [9-121 and high-performance liquid chromatographic (HPLC) methods [ 13-231 have been widely used for the determination of serum or plasma levels of mexiletine. GC methods are sensitive and specific but rather time-consuming, and require equipment that is not routinely available in clinical laboratories. Most HPLC methods need either fluorescence detection [ 13,16,19,20,23] or derivatization [ 14,16,18,19,20,23], and only some use UV detection with no need for either [ 15,17,21,22]. The aim of this study was to develop an HPLC assay for the simultaneous determination of mexiletine hydrochloride and mexiletine metabolites. The method had to be rapid, simple and accurate in the therapeutic range and inexpensive, to allow for easy monitoring of the drug in clinical practice.