Sensitivity Enhancement for Separation-Based Analytical Techniques Utilizing Solid-Phase Enrichment Approaches and Analyte Derivatization for Trace Analysis in Various Matrices

Despite the fact that strong routine separation methodologies can give reliable specificity and validity at usual working pharmaceutical concentrations, they may fail at very low concentration levels. This poses considerable challenges for researchers investigating product purity and therapeutic drug monitoring. Sensitivity enhancement procedures are thus required to maximize the performance of separation techniques. Solid-phase extraction/solid-phase enrichment (SPE/SPEn) and pre-, post-, and in-column derivatization, as well as the use of sensitive detection devices, are the simplest strategies for improving sensitivity of separation-based analytical techniques. Large-volume injection of samples with online SPE/SPEn coupled with separation techniques increased sensitivity and improved detection as well as quantification limits without affecting peak shape and system performance. Although the primary purpose of derivatization is to improve sensitivity and selectivity, greener derivatization is growing in popularity and should be considered in analytical chemistry. In general, two strategies are essential for accomplishing greener derivatization goals. The first is the search for and use of ecologically acceptable derivatizing reagents, solvents, and reaction conditions. The second is miniaturization and automation of analytical methods. This review discusses significant advances in separation-based analytical techniques, specifically enrichment approaches and detector signal improvement for pharmaceutical quantification in various matrices at very low concentration levels. As a result of improved analytical systems setup in drug assays, the possibility of high-throughput analyses was also highlighted.