The invention relates to a method for differentially hemolyzing whole blood. It discloses method for detecting an analyte in a liquid sample known or suspected to comprise red blood cells and suspected or known to comprise eukaryotic cells, the method comprising the steps of processing said liquid sample with a membrane solubilizing agent under conditions appropriate to lyse cell membranes of red blood cells and at the same time not to cause precipitation of sample constituents, subjecting the processed sample to a chromatographic separation, and detecting the analyte. The differential hemolysis of red blood cells is of advantage in a method of detecting an analyte in a liquid sample that may comprise both erythrocytes as well as nucleated cells. The differential solubilization of red blood cells can be easily combined with an online detection methodology, like LC-MS, and is advantageous in the detection of many analytes, e.g. in the detection of folate or of immunosuppressive drugs, like tacrolimus or sirolimus.