Our results obtained from both positive and negative ion modes indicate LN2 quenching is indispensable to preserve metabolites, but storage at low temperature (even at -80 °C) should be minimized to retain cell metabolites. Although rapid drying in vacuum at room temperature can largely retain cell metabolites, cells need to be immediately analyzed after drying because storage at -80 °C can still change cell metabolites. Compared with freeze drying, which forms small ice crystals with porous structures and large surface areas, drying at room temperatures is less effective to remove water molecules from cells . It is possible that residual water content in cells as well as the condensed water, which could be possibly formed during the defrosting process (e.g., during the transition from the -80°C freezer to the desiccator and due to residual moisture in the desiccator), could result in partial rehydration of dried cells lead to reactions such as through reactivated enzymatic activities and hydrolysis reactions.