Metabolomics is a tool to decipher and understand the physiological state of a cell or organism. Recently, LC/MS emerged as the prevalent analytical technique of choice. However, there is still significant potential for improved robustness and ease of use. This application note demonstrates that a biocompatible flow path has significant advantages over stainless steel. These advantages were proven by comparing the Agilent 1290 Infinity II Bio LC and Agilent 1290 Infinity II LC. The 1290 Infinity II Bio LC showed improved peak shape and resolution forphosphorylated compounds such as nucleotides and sugar phosphates without apparent adsorption effects, compared to the 1290 Infinity II LC. Excellent retention time RSD values of 0.1% were generated for intracellular metabolite extracts derived from Saccharomyces cerevisiae. These data suggest that essential metabolites for physiological parameters such as the adenylate energy charge could be analyzed consistently. Together, these results show that the 1290 Infinity II Bio LC is the perfect choice for a seamless and robust analysis in metabolomics.