Shane R. Needham

Microflow LC–MS-MS has seen a surge of attention, development, and popularity among research scientists and bioanalysts over the last few years. The potential of this technology to provide better sensitivity, less solvent waste, near-zero dead volume, and high through-put are a big part of this renewed interest. However, microflow LC techniques are hardly a new idea. More than 40 years ago, in 1974, a group at Nagoya University in Japan first developed a microcolumn liquid chromatography system, elements of which can be found in today’s commercial products. With the advances in technology over the last several years, development and implementation of this technique have been kicked into high gear. In this article, we discuss the history of microflow LC–MS-MS, the current state of the art, and where the future might lead for this rapidly growing technology.

When selecting the optimum phase for SEC separations, several key column parameters must be considered carefully.

HPLC–MS-MS is the go-to technique for high throughput analysis of small molecule therapeutics, metabolites, and biomarkers. Through technological advancements in the last decade, developing quality methods for a novel analyte in the contract research environment has become easier and faster than ever. Increasingly shorter run times, higher sensitivity, and greater separation have all become possible in a standard method. This is, in part, due to column technologies that have enabled the standardization of the method development process. Method efficiency and productivity are also improving because of emerging column technologies such as sub-2 µm particle size coupled with UHPLC–MS-MS, superficially porous particle columns, and microflow HPLC–MS-MS. Increasing efficiency and productivity in high throughput bioanalysis is becoming more important as the applications for HPLC–MS-MS expand to large molecules such as peptides, proteins, and oligonucleotides.

Guest author S.R. Needham describes an HPLC–tandem MS method that rapidly analyzes drugs and isobaric metabolites in complex matrices.