A detailed protocol using liquid chromatography coupled to tandem mass spectrometry (LC/MS/MS) is described for the determination of the total homocysteine (HCY) in plasma. Sample preparation is simple and relies on the complete reduction of any homocystine ((HCY)2 ) or protein-bound homocysteine, followed by the plasma protein precipitation. Any factor influencing the measurement is addressed. The protocol is robust and suitable for large-scale routine determinations.
