Beyond Analyte Recovery: A Holistic Review of Conventional and Miniaturized Extraction Techniques for Pharmaceutical Analysis in Environmental Samples

Abstract

Abstract The presence of pharmaceuticals in the environment has become a significant analytical and ecological concern because of their continuous release, persistence, and potential adverse effects. Their occurrence at trace levels, combined with the complexity of environmental matrixes, necessitates efficient extraction and preconcentration prior to instrumental determination. This review critically evaluates the performance of conventional extraction techniques, namely, liquid–liquid extraction (LLE) and solid-phase extraction (SPE), compared with their miniaturized versions for the extraction and preconcentration of pharmaceuticals in environmental samples. Representative peer-reviewed studies were critically evaluated, focusing on reported extraction recoveries, enrichment factors, and practical advantages and limitations. Conventional LLE and SPE have recoveries ranging from 9 to 120% and are limited by higher solvent consumption and longer processing times. Miniaturized techniques generally achieved improved enrichment (7.3–273.0-fold enrichment) and recoveries between 9.4 and 229.0% while significantly reducing solvent usage and enhancing sensitivity. Recoveries exceeding the accepted range may reflect matrix effects or analytical bias and should, therefore, be interpreted with caution. Beyond recovery and enrichment trends, this review also synthesizes and compares extraction techniques based on practical performance characteristics, including simplicity, rapidness, selectivity, versatility, greenness, and reusability to support informed method selection. While miniaturized techniques excel in rapidness, greenness, and selectivity, the conventional techniques remain the best in terms of simplicity and versatility. The review confirms that no single extraction technique can be regarded as universally superior. Therefore, method selection should balance the analytical performance with operational practicality, environmental sustainability, and cost. Continued improvement of extraction techniques is recommended to further enhance the pharmaceutical monitoring in environmental systems.