Herein, reduced graphene oxide (RGO) has been utilized as an efficient sorbent in microextraction by packed sorbent (MEPS). The combination of MEPS and liquid chromatography-tandem mass spectrometry has been used to develop a method for the extraction and determination of three local anesthetics (i.e. lidocaine, prilocaine, and ropivacaine) in human plasma and saliva samples. The results showed that the utilization of RGO in MEPS could minimize the matrix effect so that no interfering peaks at the retention times of the analytes or internal standard was observed. The high extraction efficiency of this method was approved by mean recoveries of 97.26–106.83% and 95.21–105.83% for the studied analytes in plasma and saliva samples, respectively. Intraand inter-day accuracies and precisions for all analytes were in good accordance with the international regulations. The accuracy values (as percentage deviation from the nominal value) of the quality control samples were between −2.1 to 13.9 for lidocaine, −4.2 to 11.0 for prilocaine and between −4.5 to −2.4 for ropivacaine in plasma samples while the values were ranged from −4.6 to 1.6 for lidocaine, from −4.2 to 15.5 for prilocaine and from −3.3 to −2.3 for ropivacaine in human saliva samples. Lower and upper limit of quantification (LLOQ, ULOQ) were set at 5 and 2000 nmol L−1 for all of the studied drugs. The correlation coefficients values were ≥0.995. The limit of detection values were obtained 4 nmol L−1 for lidocaine and prilocaine, and 2 nmol L−1 for ropivacaine.
