ABSTRACT
A stability-indicating UPLC method has been developed
and validated for the determination of related substances of Posaconazole with its
four related substances (Hydroxytriazole, Tosylated compound, Deshydroxy posaconazole
and Benzylated posaconazole) in the drug substance. Forthwith simple UPLC chromatographic
separations were achieved on a Waters Acquity BEH shield C18 (100 mm
length, 2.1 mm internal diameter and 1.7 μm particle size) with a mobile phase containing 0.1% Orthophosphoric acid (i.e. 1 mL in 1000 mL water) in gradient combination with acetonitrile (ACN) at a flow
rate of 0.5 mL/min and the eluent were monitored at 210 nm. As a result, the resolution
of Posaconazole from any of impurities was found to be greater than 2.0. The test
solution and spiked solutions were found to be stable in the diluent for 48 h. For
the purpose method to be stability indicating, forced degradation studies were conducted
and the method resolved the drug from its known impurities, stated above, and from
additional impurities generated when POS subjected to forced degradation; the
mass balance was found close to 100%. Regression analyses indicate correlation coefficient
value greater than 0.999 for Posaconazole and its known impurities. The LOD for
Posaconazole and the known impurities was at a level below 0.05%. The method has
shown good, consistent recoveries for known impurities (89% - 106%). To summarise,
the method was found to be accurate, precise, linear, specific, sensitive, rugged,
robust, and stability-indicating.