Background: Supercritical Fluid Chromatography (SFC) is an eco-friendly and sensitive
method for the determination of various polar and non-polar analytes. SFC is offering advantage of low
solvent consumption. The aim of this paper is to describe a novel SFC method for determination of montelukast
in formulation and exploring the possibility of the method for the degradation study of montelukast.
Methods: Methanol was used as solvent for analyte. Supercritical carbon dioxide (SC-CO2) was used as a
mobile phase at a flow rate of 1.9 mL/min with 5% v/v methanol as co-solvent. Chromatographic separation
was achieved on Zorbax SB Phenyl column (150 mm X 4.6 mm, 5 µm) with monitoring of the eluent
at 238 nm using UV detector. The column temperature and back pressure of the system were 400C and
200 bar respectively. The physical properties like densities and polarities of the mobile phase were optimized
from the effect of pressure, temperature and co-solvent concentration on chromatographic parameters.
Validation of the developed method was carried out as per ICH guidelines in terms of selectivity,
linearity, precision, recovery, robustness and solution stability.
Results: The retention time for montelukast was 8.71 ± 0.14 min. Beer-Lambert’s law was found to obey
in the concentration range 10-250 µg/mL with correlation coefficient 0.999. The method was found to be
precise, accurate and robust with % RSD of less than 2%. Assay of montelukast was found to be 100.43
and 96.17% in formulations containing 10 mg and 5 mg of montelukast respectively. Montelukast was
found to get degraded in acid, photo and peroxide stress conditions, while no degradation was observed in
base and thermal stress conditions.
Conclusion: The method was successfully applied for the assay and content uniformity of different marketed
formulations having a dose of 10 or less than 10 mg of montelukast. The developed method proved
its potential for the separation of degradation products of montelukast in various degradation conditions.