Integration of microfluidic LC with HRMS for the analysis of analytes in biofluids: past, present and future (Waters)

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.

Over the last 20 years LC–MS/MS has established itself as the dominant technique for bioanalysis, metabolite identification and biomarker monitoring [1–5]. The specificity and selectivity of tandem quadrupole MS confers great confidence in the quality of the quantitative data produced, which is required for pharmaceutical compound development, clinical diagnostics and biomarker validation. The ability of LC to resolve isomers and enantiomers perfectly complements that of MS to resolve compounds with similar/identical chromatographic properties by mass-to-charge ratio or even to resolve analytes with the same nominal mass but a different elemental composition. The time domains of the two technologies are also highly complementary. Thus, chromatographic separations occurring in seconds fit well with MS data acquisition times which are measured in milli- or micro-seconds allowing the mass spectrometer to accurately define and monitor the chromatographic separation, without compromising data quality or sensitivity.

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