Glyphosate (n-(phosphomethyl) glycine) is a non-selective, systemic herbicide absorbed by foliage. It is widely used in agriculture, horticulture and silviculture applications. Due to its high polarity, glyphosate could be adsorbed in the liver of herbivores eating contaminated foliage/cereals. Therefore, it is a molecule/matrix combination to be measured for the MACP of EU. Considering this molecule/matrix combination, we face two major problems. First of all, glyphosate is a very hydrophilic molecule with 4 different pKa and complicate its chromatographic separation which is known to be difficult. A derivatization step with FMOC counter this problem [1] and allow to achieve lower LOQ. The second one, liver is a very complex polar matrix which shows a high variability through its composition between individuals and between different species. The clean-up strategy includes several generic clean-up steps to take into account this variability.The method start with the addition of glyphosate C13 as internal standard to 5 g of liver then, glyphosate is extracted with 10 ml of a solution composed of water/methanol (80/20; v/v). After homogenization and centrifugation, the supernatant is withdraw then, dichloromethane is added and followed by a new centrifugation. This step is reiterated to assure a maximum fat elimination. The supernatant is then purified with a solid phase extraction (SPE) on a Weak Anion Exchange cartridge. The glyphosate is eluted by basified methanol and then dried with a nitrogen stream. One milliliter of water is added in the tube before derivatization with FMOC and injected on a UHPLC-MS/MS system in ESI+ mode.Due to the derivatization, the polarity of glyphosate is reduced, which allows us the injection on a C18 column. The elution is performed by an elution gradient composed of binary mobile phases with 5 mM ammonium acetate in water/methanol (90/10; v/v) for phase A and methanol/water (90/10; v/v) for phase B.The glyphosate maximal residue limit (MRL) in liver was fixed at 0.05 mg/kg by the Commission Regulation (EU) N°212/2013. Our analytical method has a limit of quantification of 0.025 mg/kg and was validated following SANCO/12571/2013 criteria. The quantification is performed by isotopic dilution leading to very good validation data with a mean recovery close to 100% and a RSD below 10%.