Introduction Local anesthetics are cationic surfactants of tertiary amine forms with an aromatic ring. They have relatively high p K a values in the range 7.5–9.0 [1, 2, 3]. They exist as a mixture of positively charged and neutral (un- charged) species depending on the pH of the aqueous solution. Despite several reports about the effects of lo- cal anesthetics on cell and/or model membranes [4, 5, 6, 7], the ratio between uncharged and charged anesthetics in aqueous solution is not accurately described in many studies, much less the ratio of both anesthetics in the membrane. The ratio of uncharged to charged anes- thetics in aqueous solution is determined by the p K a value and pH value of the solution. On the other hand, it is considerably difficult to know the ratio of those par- titioned into the membrane. This difficulty arises because there is no restraint in the quantities of the species par- titioned into the membrane so long as the condition of electroneutrality holds only in the membrane. Hitoshi Matsuki Michio Yamanaka Hiroshi Kamaya Shoji Kaneshina Issaku Ueda Dissociation equilibrium between uncharged and charged local anesthetic lidocaine in a surface-adsorbed film Received: 10 February 2004 Accepted: 14 May 2004 Published online: 6 August 2004 Ó Springer-Verlag 2004 Abstract The dissociation equilib- rium between uncharged local anes- thetic lidocaine (LC) and charged local anesthetic LC (LCH + ) in a surface-adsorbed film was investi- gated by measuring the surface tension and pH of aqueous solutions of a mixture of hydrochloric acid and LC. The surface tension values decreased slightly with increasing total molality m t at 0 £ X 2 £ 0.5, where X 2 is the mole fraction of LC in the mixture, while they decreased rapidly with increasing m t at 0.5<X 2 £ 1. It was shown from the pH measurements that almost all LC molecules were changed into LCH + ions by protonation at 0 £ X 2 £ 0.5 and both forms coex- isted only at 0.5<X 2 £ 1. The quantities of the respective LC and LCH + transferred from the aque- ous solution to the adsorbed film, i.e., their surface densities, were cal- culated by applying the thermody- namic equations derived to the surface tension and pH data. A greater quantity of LC than LCH + existed in the adsorbed film at the coexisting composition. The parti- tioning behavior of LC and LCH + in the adsorbed film was character- ized by three composition regions: (1) slight partitioning of low surface- active LCH + in the region at 0 £ X 2 £ 0.5, (2) preferential parti- tioning of LC at 0.5<X 2 <around 0.7, and (3) negative partitioning of LCH + at around 0.7 £ X 2 £ 1. The present results clearly indicate that uncharged local anesthetics transfer into hydrophobic environments such as cell membranes more than charged ones. Keywords Surface tension Æ Surface- adsorbed film Æ Uncharged local anesthetic Æ Charged local anes- thetic Æ Preferential partitioning Æ Negative adsorption Colloid Polym Sci (2005) 283: 512–520 DOI 10.1007/s00396-004-1177-1 ORIGINAL CONTRIBUTION H. Matsuki (&) Æ S. Kaneshina Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, 2-1 Minamijosanjima-cho, 770-8506 Tokushima, Japan E-mail: matsuki@bio.tokushima-u.ac.jp Tel.: +81-88-6567520 Fax: +81-88-6553162 M. Yamanaka Department of Chemistry, Faculty of Science, Kyushu University, 4-2-1 Ropponmatsu, Chuo-ku, 810-8560 Fukuoka, Japan H. Kamaya Æ I. Ueda Department of Anesthesia, Department of Veterans Administration Medical Center and University of Utah School of Medicine, Salt Lake City, UT 84148, USA