Sensitive determination of d-carnitine as enantiomeric impurity of levo-carnitine in pharmaceutical formulations by capillary electrophoresis–tandem mass spectrometry

Abstract

In this work, capillary electrophoresis–electrospray ionization-tandem mass spectrometry was applied to the determination of l- and d-carnitine in pharmaceutical formulations. A simple sample treatment procedure consisting of the use of a dilution or an extraction step with water was employed prior to derivatization with 9-fluorenylmethoxycarbonyl (FMOC). The method was validated in terms of selectivity, linearity, accuracy, precision and sensitivity, with a LOD of 10 ng mL −1 for each enantiomer, which was enough to detect enantiomeric impurities up to 0.002% of d-carnitine with respect to the main enantiomer ( l-carnitine). Eleven pharmaceutical formulations were analyzed including ampoules, oral solutions, sachets, and tablets. Results showed contents for carnitine comprised between 77 and 101% with respect to the labeled ones in the case of those formulations marketed with the racemate, and from 97 to 102% in those cases where the single enantiomer ( l-carnitine) was employed as active ingredient. Percentages for the enantiomeric impurity ( d-carnitine) ranging from 0.6 to 1.3% were obtained exceeding the limits established for impurities in drug products. These results corroborate the need of validated analytical methodologies enabling the quality control of pharmaceutical formulations containing carnitine.