Preparation of a Ketoconazole Ion-Selective Electrode and Its Application to Pharmaceutical Analysis

Abstract

Ketoconazole,-2-(1H-imidazole-1-ylmethyl)-1,3-dioxolan-4-yl]methoxyl]-phenyl]piperazine (I), is a highly effective broad-spectrum antifungal agent which is used to treat a wide variety of superficial and systematic mycoses.1,2 It has an advantage over other imizazole derivatives of producing adequate sustained blood levels following oral administration. Meanwhile, ketoconazole may cause some changes in cytochrome P-450-dependent monooxygenase activities 4,5 as well as in epoxide hydrolase activity. 6 Due to the vital importance of ketoconazole determination in biological fluids and in pharmaceutical preparations, several chromatographic 3,7-11 and spectroscopic [12][13][14][15][16] methods for its quantitative determination have been reported. However, some of these methods need expensive equipment and/or are time consuming.On the other hand, ion-selective membrane electrodes which are selective to a variety of ionic drugs have attracted increasing interest because of their potential use in pharmaceutical analysis. [17][18][19] The inherent advantages of ion-selective electrodes (ISEs) are simplicity, short measurement time, low cost, adequate precision and accuracy, adequate detection limits, wide analytical range, and particularly the ability to measure the activity of various drugs selectively, and in most cases, without prior separation of the drug of interest from the formulation matrix in colored or cloudy samples. These make ISE potentiometry very attractive for pharmaceutical analysis. [20][21][22] In this paper, we describe a simple potentiometric PVC-membrane sensor for the determination of ketoconazole in pharmaceutical preparations and in biological matrices. The membrane used in this electrode was made from liquid-plasticized PVC and was based on a water-insoluble ketoconazole-tetraphenylborate ion pair as an ion-exchanger. Experimental ReagentsAll of the chemicals used in this study were of the highest purity available and were used without further purification, except for vacuum drying over P2O5. Doubly distilled deionized water was used throughout. Reagent-grade ketoconazole as well as tablets and creams containing 200 mg and 2% of the drug, respectively, were obtained from Behvazan pharmaceutical company, Rasht, Iran. Reagent-grade nitrophenyl octyl ether (NPOE), tetrahydrofuran (THF), sodium tetraphenylborate (NaTPB), high relative molecular weight PVC and the nitrate salts of all cations used (all from Merck) were used as received.A working standard solution of 0.05 mol dm -3 ketoconazole was prepared by dissolving 0.2657 g of pure drug in ca. 6 cm 3 of 0.2 mol dm -3 hydrochloric acid and diluting to the mark with water in a 10 cm 3 calibrated volumetric flask. More dilute solutions were prepared by further dilution of appropriate volumes of the standard solution with water.The ion exchanger was prepared by shaking 5.0 cm 3 of a 0.01 mol dm -3 ketoconazole solution with an equal volume of a 0.01 mol dm -3 of sodium tetraphenylborate.The resulting ketoconazole-tetraphenylborate ion-pair precip...

Potentiometric PVC membrane sensor for the determination of phenylephrine hydrochloride in some pharmaceutical products

“…The proposed membrane sensor proved to be useful for the assay of phenylephrine hydrochloride (PEHCl) content of pharmaceutical preparations by using the two methods of standard addition method and direct potentiometry [18][19][20][21]. As the application of electrode, 2 ml of nasal drop of phenylephrine (0.5 g per 100 ml) was diluted up to 10 ml and then analyzed by the proposed electrode.…”

One decade of research on ion-selective electrodes in Iran (1996–2006)

“…Histamine [265], histidine [266], imidazole [267,268], ketamine [269], ascorbic acid [270], oxalate [271], triamterene [272], naphazoline [273], valproate [274], cystein [275], theophiline [276], sulfosalicylic acid [277], thiosalicylic acid [278], salicylate [279,280], ketoconazole [281], clotrimazole [282], cimetidine [283], diclofenac [284], atenolol [285], picrate [286], linear alkylbenzene sulfonate [287,288], sodium dodecylsulfate [289][290][291], dodecylbenzene sulfonate [292] aresepecies the sensors of which have been introduced by Iranian researchers.…”

“…As it is seen from Table 3, these sensors were based on ionophores like different complexes of iron(III) [265], iron(II) [270], copper(II) [271], zirconyl(IV) [277], nickel(II) [279], tin(IV) [280], lead(II) [275], aluminum(III) [278] and manganese(III) [265], 2,4,6- ClO 4 -, SCN -PME/ CGE [279] triphenylthiopyrilium perchlorate [267], 4-methyl-2,6-diphenylthiopyrylium [268], ion-exchanger sites [269], tetraphenylborate ion [272], tetraphenylborate [273], conducting polypyrrole films [274], 2,6-bis(phenyl)-4(phenyl) 3H-thiopyran [276], phthalocyanine [278], ketoconazoletetraphenyl borate ion pair [281], phosphomolybdate [282], phospoho tungstate [283], hexadecylpyridinium bromide [284], tetrakis(p-chlorophenyl) borate [285], polypyrrole [287,290], and hyamine [288], polyaniline-dodecylsulfate [289], cetylpyridinium cation [291], polyaniline [292], which have different natures and hence different selection mechanisms.…”

Triiodide Ion-Selective Polymeric Membrane Electrode Based on a Ketoconazole-Triiodide Ion Pair

“…On the other hand, the incorporation of STPB as a lipophilic anionic additive (electrode No. 11) indicate a subNernstian behavior with a narrow linear range probably due to strong interaction between the tetraphenylborate(TPB) anion and protonated KC resulting in ion-pair formation [31].Thus, due to Nernstian behavior and wide linear range a membrane with a PVC : NPOE : (KCH 2 )(I 3 ) 2 ratio of 30 : 69 : 1 was chosen for further studies. This membrane displays remarkable selectivity and sensitivity for I À 3 ion over most common anions.…”