Development of Liquid-Liquid Extraction-Assisted, Derivatization-Free Gas Chromatography Integrated With the Flame...

Marketed cream formulations contain fatty acids as core constituents, required for its texture, uniformity, shelf life, and skin penetration. Given their importance in the cosmetic and pharmaceutical industries, real-time quantification and analysis of these compounds are crucial for assessing authenticity and ensuring compliance with regulatory specifications. In the present analysis, we employed gas chromatography with flame ionization detection (GC-FID) due to its sensitivity, robustness, and quantitative reliability. Overcoming the traditional method for fatty acid determination, we analyzed the sample without derivatization to fatty acid methyl esters (FAMEs). The derivatization step was initially omitted to simplify sample preparation, reduce analysis time and reagent consumption, and minimize the potential errors associated with incomplete esterification or degradation of unstable fatty acids during derivatization. Direct analysis was performed by dissolving the extracted sample in isopropyl alcohol and then filtering and injecting it into the GC-FID system under optimized chromatographic conditions. The optimized method was used for the concurrent quantification of lauric, myristic, palmitic, oleic, and stearic acids. The validation of the present work was executed in alignment with ICH Q2(R1) requirements. The method was further expanded to analyze real cream samples, thereby validating the accuracy of fatty acid profiling for routine quality control.