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

Abstract

This 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.

Detection and quantification of antiviral drug tenofovir using silver nanoparticles and surface enhanced Raman spectroscopy (SERS) with spatially resolved hotspot selection

“…SERS has emerged as a highly sensitive technique for detecting drugs by generating unique vibrational spectra for specific molecules (Thobakgale et al, 2022). This approach offers a considerable advantage over conventional methods such as LC-MS/MS, which involve complex instrumentation and sample preparation (Lin et al, 2023). Other methods of detection of aqueous TFV include squarewave voltammetry where Festinger and coworkers reported limits of detection as low as 1.35 × 10 −7 M (39 ng/mL) and 4.86 × 10 −8 M (14 ng/ mL) (Festinger et al, 2022).…”

“…Other methods of detection of aqueous TFV include squarewave voltammetry where Festinger and coworkers reported limits of detection as low as 1.35 × 10 −7 M (39 ng/mL) and 4.86 × 10 −8 M (14 ng/ mL) (Festinger et al, 2022). Chiral separation phase (CSP) LCMS of enantiomeric mixtures of a prodrug form of tenofovir, tenofovir disoproxil fumarate (TDF), reported limits of detection of 1.5 ng/ mL and 1.2 ng/mL for the R-and S-TDF enantiomers, respectively (Lin et al, 2023). While these are very impressive limits of detection, these methods require complex instrumentation and skill.…”