Gas-liquid chromatographic determination and pharmacological studies of six clinically-used local anesthetics.
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 m x 2 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-Sørensen 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.
Lau
O W
OW
Department of Chemistry, Chinese University of Hong Kong, Shatin, New Territories.
Chan
K
K
Wong
Y C
YC
D000278:Administration, Buccal; D000779:Anesthetics, Local / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D002849:Chromatography, Gas / Q000379:methods; D006801:Humans; D007408:Intestinal Absorption; D007700:Kinetics; D008297:Male; D009061:Mouth Mucosa / Q000378:metabolism
D000779:Anesthetics, Local