Sensitivity Enhancement for Separation-Based Analytical Techniques Utilizing Large Volume Injection and Analyte Derivatization for Trace Analysis in Bio-Fluids

Despite the fact that strong routine separation methodologies can give reliable specificity and validity at usual working pharmaceuticals concentrations, they may fail at very low concentration levels. This poses considerable challenges for researchers inves-tigating product purity and therapeutic drug monitoring. Sensitivity enhancement pro-cedures are thus required to maximize the performance of separation techniques. Large volume injection, solid phase extraction/solid phase enrichment (SPE/SPEn), pre-, post-, and in-column derivatization, as well as the use of sensitive detection devices are the simplest strategies for improving sensitivity of the 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.