The use of electrospray LC-MS and LC-MS/MS for the quantitative determination of two low molecular weight (< 500 Da) organic compounds in human plasma (Lovastatin) and cell supernatants (Arachidonic acid) and medium molecular weight (> 2000 Da) endogenous peptides (Endothelins) in supernatants of human umbilical vein endothelial cell cultures is reported. These methods make use either of deuterium labelled or structurally similar molecules as internal standards for quantitation and one or more pre-purification steps previous the LC-MS analysis. Linear calibration curves and detection limits around 50 pg ml(-1) were obtained in all three cases.