Development and validation of LC/MS method for the determination of meclizine enantiomers in pharmaceutical formulations.

An enantiomeric separation of meclizine enantiomers by liquid chromatography with tandem mass spectrometry LC-MS method was developed and validated for the analysis of Meclizine enantiomers. Enantiomeric resolution of the drug products were successfully achieved on a Phenomenex® lux cellulose 1 C18 (250 mm × 4.6 mm i.d, 5 µm particle size) column with mobile phase consisting of acetonitrile: 5 mM ammonium format pH (5.5) adjusted with formic acid (90:10) (v/v), and a flow rate of 0.4 mL/min. The developed method provided linear responses within the concentration range 1-5 ng/mL, and regression analysis showed a correlation coefficient value (r2) of 0.999. The optimized mobile phase separated (+) Meclizine at 1.58 min and (-) Meclizine at 2.20 min, respectively. The LC/MS method was validated as per ICH guidelines with respect to specificity, precision, linearity and robustness. Limit of detection (LOD) and limit of quantification (LOQ) were found to be 1.0 ng/mL and 5.0 ng/mL respectively. The proposed method is suitable for analysis of meclizine enantiomers in pharmaceutical formulations and quality control analysis.

Characterization of the Oxidative Degradation Product of Darunavir by LC-MS/MS.

A rapid, selective, and reliable LC-MS(n) method has been developed and validated for the isolation and structural characterization of the degradation product of darunavir (DRV). DRV, an HIV-1 protease inhibitor, was subjected to intrinsic oxidative stress conditions using 30% hydrogen peroxide and the degradation profile was studied. The oxidative degradation of DRV resulted in one degradation product. The unknown degradation product was separated on a Hibar Purospher C18 (250 mm × 4.6 mm; 5 µm) column by using 0.01 M ammonium formate (pH 3.0) and acetonitrile as mobile phase in the ratio of 50:50, v/v. The eluents were monitored at 263 nm using a UV detector. The isolated degradation product was characterized by UPLC-Q-TOF and its fragmentation pathway was proposed. The proposed structure of the degradation product was confirmed by HRMS analysis. The developed stability-indicating LC method was validated with respect to accuracy, precision, specificity/selectivity, and linearity. No prior reports were found in the literature about the oxidative degradation behavior of DRV.