PubMed · 8917152
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J W Richards. 1996. Cryptic tonsillitis.. https://pubmed.ncbi.nlm.nih.gov/8917152/
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The interaction of the tertiary amine drugs chlorpromazine and dibucaine in their cationic form with carboxyl groups at the membrane surface is studied at concentrations relevant to anesthesia. Spin-labeled stearic acid is used both to provide the carboxyl groups and to monitor binding and ionization behavior in egg lecithin liposomes. Membrane anesthetic concentrations are spectrophotometrically obtained. They are shown to determine the drug influence on carboxyl groups at the membrane surface, independently of aqueous concentrations. The intramembrane association constants (related to the usual aqueous phase ones through the partition coefficient) of the drugs with fatty acids are determined. The same value (10(2) M-1) is obtained for both drugs, suggesting that it is approximately the same for all tertiary amine local anesthetics. pH titrations of anesthetic-treated spin-labeled membranes are performed. The observed shifts in the fatty acid pK are higher than can be produced assuming uniform distribution of the drug in the membrane surface, implying that there is an increased affinity of local anesthetics for superficial carboxyl. This affinity could account for the resting block of voltage-gated Na+ channels. Under these considerations, local anesthetic binding sites at voltage-gated Na+ channels and at sarcoplasmic reticulum Ca(2+)-ATPase are proposed.
A simple method for analysis of five local anaesthetics in blood was developed using headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry-electron impact ionization selected ion monitoring (GC-MS-EI-SIM). Deuterated lidocaine (d10-lidocaine) was synthesized and used as a desirable internal standard (I.S.). A vial containing a blood sample, 5 M sodium hydroxide and d10-lidocaine (I.S.) was heated at 120 degrees C. The extraction fiber of the SPME system was exposed for 45 min in the headspace of the vial. The compounds adsorbed on the fiber were desorbed by exposing the fiber in the injection port of a GC-MS system. The calibration curves showed linearity in the range of 0.1-20 microg/g for lidocaine and mepivacaine, 0.5-20 microg/g for bupivacaine and 1-20 microg/g for prilocaine in blood. No interfering substances were found, and the time for analysis was 65 min for one sample. In addition, this proposed method was applied to a medico-legal case where the cause of death was suspected to be acute local anaesthetics poisoning. Mepivacaine was detected in the left and right heart blood samples of the victim at concentrations of 18.6 and 15.8 microg/g, respectively.