A gas-liquid chromatographic method was developed for the simultaneous assay of six local anesthetics, including amethocaine, bupivacaine, etidocaine, lignocaine, mepivacaine and prilocaine, in biological samples. These drugs and internal standard (clomipramine) in basified samples were extracted into 5 ml n-hexane, and the extract was analyzed by a temperature programming method (the column temperature was kept at 210-degrees-C for 5 min, then raised to 280-degrees-C at the rate of 10-degrees-C/min) using a 3% W/W SP 2250 glass column (2 mx2 mm i.d.) connected to a nitrogen sensitive detector. The injector and detector temperature were maintained at 300-degrees-C. The pKa values, partition coefficients (K) and buccal absorptions of six local anesthetics were determined. The results showed that the onset of action and duration could be shown to be dependent on the pKa values and partition coefficients, respectively. A relatively good positive correlation (r = 0.991) was observed between the percentage of buccal absorption at pH 7.4 and the logarithms of K in n-hexane-Sorensen buffer system, and hence the more lipid soluble the local anesthetic, the greater the buccal absorption. The buccal absorption test supplemented by the n-hexane-buffer partition coefficient could be used as indicators for the ability of the anesthetics to penetrate biological barriers. The lipid penetration of the drugs, and thus their pharmacological action, is also influenced by the pKa values of the anesthetics.
