Estimation of the effect of the acidosis and alkalosis on the anesthetic potency of local anesthetics by biopartitioning micellar chromatography and micellar electrokinetic chromatography.
Local anesthetics are hydrophobic compounds and weak bases with protonation constants ranged between 7.5 and 8.8. These drugs block reversibly nerve conduction near their site of application or injection and thus produce temporary loss of feeling or sensation in a limited area of the body. The efficacy of anesthetic blockade of local anesthetics depends on the charged/uncharged form ratio and the hydrophobicity of the compounds. In addition their toxicological effects have been reported to be highly dependent on the physiological pH. Biopartitioning micellar chromatography (BMC) and micellar electrokinetic chromatography (MEKC), that use micellar solutions as mobile phases, have proven to be useful for describing the biological behavior of different kind of compounds. In this paper, relationships between the retention data in BMC and MEKC using Brij35 as surfactant (at pH 7.4) and some pharmacodynamic parameters of local anesthetics are obtained. These models are compared with those obtained using an immobilized artificial column (IAM). Finally, the effect of the corporal pH in situations of acidosis and alkalosis on the pharmacological and toxicological properties of local anesthetics is studied using the retention of compounds in BMC at different mobile phase pH values.
Canós-Rius
N
N
Dpto. Química Analítica, Facultad de Farmacia, Universitat de València, C/ Vicente Andrés Estellés s/n, 46100 Burjassot, Valencia, Spain.
Martín-Biosca
Y
Y
Sagrado
S
S
Villanueva-Camañas
R M
RM
Medina-Hernández
M J
MJ
D000138:Acidosis; D000471:Alkalosis; D000779:Anesthetics, Local / Q000378:metabolism / Q000494:pharmacology*; D002853:Chromatography, Liquid / Q000379:methods; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D021281:Quantitative Structure-Activity Relationship
D000779:Anesthetics, Local