engleski

Comparison of HPTLC methods with densitometric detection and HPLC-DAD methods for determination of related substances and impurities in process control of the synthesis of crude pantoprazole sodium

Pantoprazole sodium is a novel substituted benzimidazole, sodium 5- (difluoromethoxy)-2-[[(3, 4-dimethoxy-2-pyridinyl) methyl] sulfinyl]-1H benzimidazole, a compound that inhibits gastric acid secretion. It belongs to a class of drugs called proton pump inhibitors. Considering two phase synthetic route of crude pantoprazole sodium (Figure 1) and potential degradation pathways, three known impurities have been considered ; two starting reactants from the first phase and one degradation product from the second synthesis phase. Both HPTLC and HPLC methods were developed, validated and adopted to the possibility of extending their applicability for determination of other potential impurities which were encountered in process control during development stage of the product. Obtained results were compared and abilities of HPTLC method were challenged. Separation was performed on Silica gel 60 F254 HPTLC adsorbent layers with tolueneacetone- ammonium, 15:7:0.15 (v/v) as mobile phase for analysis of samples from the first phase and with chloroform-acetone-ammonium, 20:2:0.2 (v/v) being used for the second phase. Both HPLC methods were developed on Waters Symmetry C18 column (250 x 4.6 mm, 5 &micro ; m particle size) with column temperature maintained at 25°C. Detection wavelength was set at 290 nm. Phosphate buffer with pH 7.0 and acetonitrile were used as mobile phase constituents. Separations are based on gradient elution as this gives better selectivity as well as higher sensitivity for late eluting peaks compared to isocratic elution.

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