title: Phenytoin speciation with potentiometric and chronopotentiometric ion-selective membrane electrodes.
abstract: We report on an electrochemical protocol based on perm-selective membranes to provide valuable information about the speciation of ionizable drugs, with phenytoin as a model example. Membranes containing varying amounts of tetradodecylammonium chloride (TDDA) were read out at zero current (potentiometry) and with applied current techniques (chronopotentiometry). Potentiometry allows one to assess the ionized form of phenytoin (pKa~8.2) that corresponds to a negatively monocharged ion. A careful optimization of the membrane components resulted in a lower limit of detection (~1.6 µM) than previous reports. Once the pH (from 9 to 10) or the concentration of albumin is varied in the sample (from 0 to 30 g L(-1)), the potentiometric signal changes abruptly as a result of reducing/increasing the ionized concentration of phenytoin. Therefore, potentiometry as a single technique is by itself not sufficient to obtain information about the concentration and speciation of the drug in the system. For this reason, a tandem configuration with chronopotentiometry as additional readout principle was used to determine the total and ionized concentration of phenytoin. In samples containing excess albumin the rate-limiting step for the chronopotentiometry readout appears to be the diffusion of ionized phenytoin preceded by comparatively rapid deprotonation and decomplexation reactions. This protocol was applied to measure phenytoin in pharmaceutical tables (100mg per tablet). This tandem approach can likely be extended to more ionizable drugs and may eventually be utilized in view of pharmacological monitoring of drugs during the delivery process.
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland.
authors.forename: Sutida
authors.initials: S
authors.lastname: Jansod
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland.
authors.forename: Majid Ghahraman
authors.initials: MG
authors.lastname: Afshar
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland. Electronic address: gaston.crespo@unige.ch.
authors.forename: Gastón A
authors.initials: GA
authors.lastname: Crespo
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Geneva, Quai Ernest-Ansermet 30, CH-1211 Geneva, Switzerland. Electronic address: eric.bakker@unige.ch.
authors.forename: Eric
authors.initials: E
authors.lastname: Bakker
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000032:analysis* / Q000378:metabolism; D015374:Biosensing Techniques; D002417:Cattle; D006863:Hydrogen-Ion Concentration; D017736:Ion-Selective Electrodes; D008567:Membranes, Artificial; D010672:Phenytoin / Q000032:analysis* / Q000378:metabolism; D011199:Potentiometry / Q000295:instrumentation*; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D008567:Membranes, Artificial; D012710:Serum Albumin, Bovine; D010672:Phenytoin
keywords: Chronopotentiometry; Perm-selective membranes; Phenytoin; Potentiometry; Speciation