Managing nonspecific adsorption to liquid chromatography hardware: A review

The choice of alternative materials over stainless steel hardware in the construction of liquid chromatography systems has unveiled the degree to which nonspecific adsorption impacts the reproducibility of LC methods. Some of the major contributors to nonspecific adsorption losses are charged metallic surfaces and leached metallic impurities, that may interact with the analyte and result in analyte loss and overall poor chromatographic performance. In this review, we describe several mitigation strategies available to chromatographers to minimize nonspecific adsorption to chromatographic systems. Alternative surfaces to stainless steel such as titanium, PEEK, and hybrid surface technologies are discussed. Furthermore, mobile phase additives used to prevent metal ion-analyte interactions are reviewed. Nonspecific adsorption of analytes is not reserved to metallic surfaces, as analytes may adsorb to the surfaces of filters, tubes, and pipette tips during sample preparation. Identifying the source of nonspecific interactions is paramount, as mitigation strategies may differ depending on what stage nonspecific losses are taking place. With this in mind, we discuss diagnostic methods that may help the chromatographer to differentiate losses resulting from sample preparation, and losses during LC runs.