Perfluorinated compounds (PFCs) are man-made chemicals for which endocrine disrupting properties and related possible side effects on human health have been reported, particularly in the case of an exposure during the early stages of development, (notably the perinatal period). Existing analytical methods dedicated to PFCs monitoring in food and/or human fluids are currently based on liquid chromatography coupled to tandem mass spectrometry, and were recently demonstrated to present some limitations in terms of sensitivity and/or specificity. An alternative strategy dedicated to the analysis of fourteen PFCs in human breast milk was proposed, based on an effective sample preparation followed by a liquid chromatography coupled to high resolution mass spectrometry measurement (LC-HRMS). This methodology confirmed the high interest for FIRMS after negative ionization for such halogenated substances, and finally permitted to reach detection limits around the pg mL(-1) range with an outstanding signal specificity compared to LC-MS/MS. The proposed method was applied to a first set of 30 breast milk samples from French women. The main PFCs detected in all these samples were PFOS and PFOA with respective median values of 74 (range from 24 to 171) and 57 (range from 18 to 102) pg mL(-1), respectively. These exposure data appeared in the same range as other reported values for European countries. (C) 2011 Elsevier Ltd. All rights reserved.