Separation and simultaneous estimation of enantiomers and Diastereomers of muscarinic receptor antagonist Solifenacin using stability-indicating Normal-phase HPLC technique with chiral stationary phase amylose tris-(3,5-dimethylphenylcarbamate).

The R,S-enantiomer impurity and diastereomer impurities (S,S-isomer and R,R-isomer) of the solifenacin (S,R-enantiomer) were effectively separated and quantified simultaneously utilizing normal-phase high-performance liquid chromatography with a chiral stationary phase consisting of amylose tris (3,5-dimethylphenylcarbamate) coated on silica-gel (Chiralpak, AD-H). The enantiomeric and stereo-selective separation was achieved within a run time of 35 minutes using a mobile phase of 'n-hexane, ethanol, and diethylamine' in an isocratic elution mode with a detection wavelength of 220 nm. The validation attributes assessed were accuracy (which showed excellent recoveries between 97.5% and 100.4%) and linearity (which was proven in the range of 0.081-1.275 µg.mL-1 , with a linear regression of 0.999). The stress testing experiments proved that the developed methodology by the HPLC technique has stability-indicating characteristics, as all closely eluting peak pairs were separated well with a resolution of 2.3 and without any interference. The proposed methodology was highly efficient in separating and simultaneously determining the chiral impurities (enantiomers and diastereomers) of the solifenacin in the release and stability sample analyses of drug substances and tablets in pharmaceutical formulations.

Separation and quantitative estimation of stereo-selective enantiomers of montelukast in pharmaceutical drug substance and tablets dosage forms by using stability-indicating normal phase-HPLC method.

Montelukast sodium (MLS) is a leukotriene receptor antagonist that relieves asthma, bronchospasm, allergic rhinitis, and urticaria. A simple, robust, and stability-indicating normal phase high-performance liquid chromatography method was developed to separate and quantitatively estimate the S-enantiomer of MLS. The chiral separation was achieved using USP L51 packing material along with a mobile phase consisting of a solvent mixture (n-hexane, ethanol, and propionic acid), a flow rate of 1.0 mL/min, a detection wavelength of 284 nm, a column temperature of 30°C and an injection volume of 20 µL. The enantiomers peaks were well separated from the peaks of the placebo, diluting solvent, MLS, and its known impurities with a resolution of more than 2.2 and with no interference. Accuracy and linearity were studied in a range of 0.36-3.597 µg/mL (0.03%-0.30%), with good recoveries between 92.5% and 96.8% and a linear regression coefficient above 0.996. The suggested chiral chromatography method is being considered as an alternative and equivalent method to the United States Pharmacopeia and European Pharmacopeia monographs. The developed method was effectively employed for the study of release and stability samples of MLS. This HPLC method is also capable of separating and estimating the stereo-selective isomers (R- and S-enantiomers) of sulfoxide impurity of MLS in pharmaceutical medicine.