Study on Quality Control of Tenofovir Disoproxil Fumarate Enantiomers by High-Performance Liquid Chromatography–Mass Spectrometry

Abstract

AbstractThis study aims at developing a high-performance liquid chromatography–mass spectrometry (LC–MS) method to analyze tenofovir disoproxil fumarate (TDF) and its pharmaceutical preparations. Several cyclodextrin mobile-phase additives were applied to reversed-phase and normal-phase chromatography, and the effects of three chiral stationary phases on the TDF separation were investigated in this study. The R-type and S-type of TDF tablets were quantitatively analyzed in the single ion monitoring (SIM) scanning mode with a Unichiral CMD column. This method has been successfully applied to the separation and quantification of TDF and its isomers. The linear ranges of (R)-TDF and (S)-enantiomer were 1–20 and 0.2–16 μg/mL, respectively. The limit of detection for (R)-TDF and (S)-enantiomer was 0.0015 and 0.0012 μg/mL, respectively. (S)-enantiomer was not detected in the formulas from all the seven manufacturers, and the drug content of each took more than 98.5% of the labeled amount, which complies with the regulations. The method shows its advantages on high sensitivity, low detection limit, good practicability, and repeatability. The proposed method may provide a novel platform for separation of TDF enantiomers and quality control of TDF raw materials and preparations.