The objective of the present investigation was to study long-term stability of lidocaine and prilocaine together with their main metabolites (i.e. 2,6-xylidine, major metabolite of lidocaine, and o-toluidine, major metabolite of prilocaine) over a storage time of 4 and 8 years at or below -20°C, respectively, in authentic human plasma samples. In this regard, the investigated analytes were extracted from the plasma samples using ultrafiltration and were subjected to gradient liquid chromatography with mass spectrometric detection with electrospray ionization. The stability studies showed that the mean deviation after 4 years storage was -3.6%, 10.3%, 8.6%, and 3.8% for prilocaine, lidocaine, o-toluidine, and 2,6-xylidine, respectively, and the mean deviation after 8 years storage was -11.1% for prilocaine and 4.5% for lidocaine. The results showed that prilocaine and lidocaine in authentic plasma samples are stable for at least 8 years and o-toluidine and 2,6-xylidine in authentic plasma samples are stable for at least 4 years at or below -20°C.
