A novel LC–MS/MS analytical method for detection of articaine and mepivacaine in blood and its application to a preliminary pharmacokinetic study

Local anaesthetics (LAs) are commonly used in surgery, especially in dentistry. They cause a transitoryinhibition of nerve signal due to the blockade ofthe voltage-gated sodium channels. LAs are administratedalone or with vasoconstriction agents, such as adrenaline. Toxicity of LAs is associated to neurologicaland cardiovascular alterations. Tachycardia, arrhythmia, tremors, tonic-clonic seizure and respiratorydepression (at high doses) are the main symptoms of intoxication by LAs. Lidocaine, articaine and mepivacaine are among the most used anaesthetics. This study aimed to fully validated a new method for thesimultaneous detection of articaine and mepivacaine in whole blood. Sample treatment consisted in aliquid-liquid extraction with phosphate buffer (pH 8, 0.1 M) and ethyl-acetate. Analysis was performed byliquid chromatography-tandem mass spectrometry in multiple reaction monitoring mode (transitions:articaine, 285→8658 m/z; mepivacaine, 247→9870 m/z; lidocaine – internal standard –, 235→8658 m/z).The method proved to be highly sensitive with limit of quantifications for articaine and mepivacaine of0.8 and 0.1 ng/mL, respectively. Accuracy and precision were always within the acceptance criteria. Thenew procedure was also successfully applied to a preliminary pharmacokinetics study.