Development of an HPLC Assay Methodology for a Desonide Cream with Chemometrics Assisted Optimization

Abstract

A new reversed-phase liquid chromatographic method for the separation and simultaneous quantification of desonide, sorbic acid, methylparaben, propyl gallate, and the major degradation product of desonide in a hydrophilic cream was developed with the aid of experimental design, resolution loss functions, and chemometrics methods. A strategy involving a screening phase and a fractional factorial design revealed the most influent chromatographic variables (pH and organic solvent content). The arc tangent resolution function was adopted as the optimization loss function. These variables were further optimized using a central composite design. Multivariate curve resolution and partial least squares regression were tested to optimize the chromatographic run time. The latter revealed to be superior in terms of precision and allowed the validation of a method with a total run time 3 times lower (approximately 8 min). The experimental design and chemometrics models enabled an efficient use of time and resources in predicting the optimum separation conditions for the desonide formulation. The validation of the resulting method according to the current ICH guidelines confirmed its selectivity, linearity, accuracy, and precision.

Keywords:

• Chemometrics
• Desonide
• Experimental design
• Pharmaceutical quality control
• Reversed-phase chromatography

Acknowledgments

Jorge M.G. Sarraguça acknowledges Fundação para a Ciência e a Tecnologia (FCT-MCTES, Portugal) for the grant SFRH/BPD/46319/2008 co-financed by QREN-POPH. This work has been supported by Fundação para a Ciência e a Tecnologia through grant no. PEst-C/EQB/LA0006/2011.

Notes

[B]: buffer concentration (mM); pH: buffer pH; %B: acetonitrile content (v/v); T: column temperature (°C); F: eluent flow-rate (mL/min).

[B]: buffer concentration (mM); pH: buffer pH; %B: acetonitrile content (v/v); T: column temperature (°C); F: eluent flow-rate (mL/min).