The HILIC method is more intrinsically adaptable to a wider variety of biological sample types including those rich with lipid and protein content. HILIC methods generally do not retain neutral lipids which therefore form a part of the injection peak. The HILIC method presented here retains and elutes complex lipids within a compressed band to minimise overlap with the small molecule profile. Proteins are precipitated in the normal course of preparing the sample for HILIC which typically requires the addition of an organic solvent to the aqueous biofluid in order to better match the initial mobile phase conditions of the method which are typically between 90% and 95% acetonitrile. The method presented here utilises a 1:3 precipitation with ACN as a compromise approximation of the 95:5 starting conditions. Caution must be taken to avoid partitioning at very high percentage of acetonitrile specifically, and especially with high salinity samples, as this can lead to phase separation. Working at 4°C instead of -20°C (as might be preferred for protein precipitation alone) can help.