Integration of Microfluidic LC with HRMS for The Analysis of Analytes in Biofluids: Past, Present and Future

Abstract

Capillary LC (cLC) coupled to MS has the potential to improve detection limits, address limited sample volumes and allow multiple analyses from one sample. This is particularly attractive in areas where ultrahigh assay sensitivity, low limits of detection and small sample volumes are becoming commonplace. However, implementation of cLC-MS in the bioanalytical-drug metabolism area had been hampered by the lack of commercial instrumentation and the need for experts to operate the system. Recent advances in microfabricated devices such as chip-cube and ion-key technologies offer the potential for true implementation of cLC in the modern laboratory including the benefits of the combination of this type of separation with high-resolution MS.

Current developments in LC-MS for pharmaceutical analysis

“…Capillary and nano-scale LC in combination with MS have the ability to address small sample sizes and provide high sensitivity information, which is particularly interesting when dealing with small sample volumes and low abundant compounds. When column dimensions are moreover reduced to 100 µm or less, there is no need for a nebulizer gas, as long as the mobile phase contains a reasonable concentration of organic modifier (15-20%) 100 . Originally, capillary and nano-scale LC were mainly used in proteomics, since in drug development, drug metabolism and pharmacokinetic (DMPK) studies, there is rarely a limitation in sample volume.…”

Metabolomics in the Context of Forensic Omics Biomarkers

“…This step can vary from direct insertion of the sample either into the detector (or more commonly into previous separation equipment), to the use of microfluidic (chip-based) devices coupled to capillary high-resolution separation tools [41], or solid-phase extraction commercial equipment on-line connected to LC-MS triple quadrupole (QqQ)arrangements [42,43]. These devices constitute a milestone in forensics equipment for analysis of small samples.…”

Quantitative mass spectrometry methods for pharmaceutical analysis

“…This could have had an influence on the final sensitivity [86]. has been carried out and numerous reviews have been published concerning new trends and developments in LC [87][88][89][90]. In the last decade, LC has evolved into ultra-high pressure liquid chromatography (UHPLC) to obtain a higher throughput.…”

“…Because of the high potential for on-site and high-throughput applications, downscaling dimensions is also a trend in LC instrumentation. Several reviews give an overview of the advances made in both column sizes and LC modules [87,93,109,110]. The major advantage of miniaturized LC set-ups is the enhanced sensitivity due to higher efficiencies, lower flow rates and minimized void volumes, which will have a positive influence on the ionization efficiency and the peak shapes [111].…”

“…Therefore, conventional HPLC systems have evolved into capillary or micro-LC and even nano-LC devices. The recent development of microfluidic chromatography and micro-chip-based systems such as the Agilent Chip Cube or Waters IonKey wherein an optimized MS interface is incorporated, offers the possibility to perform automated, robust and very sensitive LC-MS analysis with a limited amount of sample [87]. More information about microfluidic LC can be found in Rainville et al, Wang et al and Šesták et al [110,112,113].…”