RESUMEN
A novel CE method was successfully applied to the enantioseparation of pantoprazole and related benzimidazoles, such as tenatoprazole, lansoprazole, and omeprazole. The chiral resolution was performed in an untreated fused-sillica capillary using a dual chiral selector system consisting of copper (II)-l-histidine (l-His) complex and hydroxypropyl-ß-CD. The primary factors affecting its separation efficiency, such as chiral selector, buffer pH, and applied voltage, were optimized. The best results were obtained by using a buffer consisting of 20 mg/mL hydroxypropyl-ß-CD, 10 mmol/L copper(II) acetate, 15 mmol/L l-histidine, 5.0 mmol/L phosphate adjusted to pH 5.0, and 15 kV applied voltage. The enantiomers of all compounds were fully resolved within 20 min with high resolutions of 3.9 to 6.2. The optimized method was extensively validated for determination of the R-(+)-enantiomer impurity in S-(-)-pantoprazole. The LOD and LOQ for the R-(+)-enantiomer were 1.0 and 2.5 µg/mL, respectively. A good linear relationship was obtained in the concentration range of 2.5-25 µg/mL with r(2 ) 0.999 for the R-(+)-enantiomer. The percentage recovery of the R-(+)-enantiomer ranged from 91.6 to 101.3. The method is capable of determining a minimum limit of 0.1% w/w of R-(+)-enantiomer in S-(-)-pantoprazole bulk samples.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/química , 2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Bencimidazoles/química , Bencimidazoles/aislamiento & purificación , Electroforesis Capilar/métodos , 2-Hidroxipropil-beta-Ciclodextrina , 2-Piridinilmetilsulfinilbencimidazoles/análisis , Bencimidazoles/análisis , Cobre , Concentración de Iones de Hidrógeno , Límite de Detección , Modelos Lineales , Pantoprazol , Reproducibilidad de los Resultados , Estereoisomerismo , beta-CiclodextrinasRESUMEN
An ephedrine-based chiral ionic liquid, (+)-N,N-dimethylephedrinium-bis(trifluoromethanesulfon)imidate ([DMP](+) [Tf(2) N](-) ), served as both chiral selector and background electrolyte in nonaqueous capillary electrophoresis. The enantioseparation of rabeprazole and omeprazole was achieved in acetonitrile-methanol (60:40 v/v) containing 60 mm[DMP](+) [Tf(2) N](-) . The influences of separation conditions, including the concentration of [DMP](+) [Tf(2) N](-) , the electrophoretic media and the buffer, on enantioseparation were evaluated. The mechanism of enantioseparation was investigated and discussed. Ion-pair interaction and hydrogen bonding may be responsible for the main separation mechanism.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Electroforesis Capilar/métodos , Efedrina/química , Omeprazol/aislamiento & purificación , 2-Piridinilmetilsulfinilbencimidazoles/química , Electroforesis Capilar/instrumentación , Enlace de Hidrógeno , Líquidos Iónicos , Omeprazol/química , Rabeprazol , EstereoisomerismoRESUMEN
Rabeprazole sodium [1] is a proton pump inhibitor, used as an antiulcerative. During the manufacturing of rabeprazole sodium, we observed an unknown impurity at levels 0.05-0.1% in HPLC analysis along with the known potential impurities. This new unknown impurity was isolated using preparative liquid chromatography. Based on the complete spectral analysis ((1)H NMR, (13)C NMR, DEPT, Mass and IR), this new impurity was designated as 2-[[(3-methyl-4-(methylthio)-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole (methylthio impurity of rabeprazole). Impurity isolation, structure elucidation and probable formation mechanism was discussed.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/química , 2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Contaminación de Medicamentos , Tecnología Farmacéutica , Cromatografía Líquida de Alta Presión , Rabeprazol , Tecnología Farmacéutica/métodosRESUMEN
The present paper demonstrates the enantiomeric separation of omeprazole and its metabolite 5-hydroxyomeprazole performed with open tubular capillary electrochromatography (OT-CEC). The protein avidin was used as the chiral selector. Avidin was immobilized by a Schiffs base type of reaction where the protein was via glutaraldehyde covalently bonded to the amino-modified wall of a fused-silica capillary, 50 microm i.d. Both racemates were baseline resolved. Resolution was 1.9 and 2.3, respectively, using ammonium acetate buffer, pH 5.8, 5% methanol, with UV-detection. These values of resolution using OT-CEC are higher than earlier published results regarding chiral separation of omeprazole and 5-hydroxyomeprazole on packed CEC. The number of theoretical plates also indicated good separation efficiency.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Electrocromatografía Capilar/instrumentación , Omeprazol/aislamiento & purificación , Avidina/química , Electrocromatografía Capilar/métodos , Reproducibilidad de los Resultados , EstereoisomerismoRESUMEN
This paper describes a validated high-performance thin-layer chromatography (HPTLC) method for simultaneous estimation of rabeprazole (RA) and domperidone (DO) in pure powder and in capsule formulations. An HPTLC method separation is achieved on an aluminum sheet of silica gel 60F(254) using ethyl acetate-methanol-benzene-acetonitrile (30:20:30:20 v/v) as mobile phase. Quantitation is achieved with UV detection at 287 nm over a concentration range of 400-1200 ng/spot and 600-1800 ng/spot with mean recovery of 99.82 +/- 0.74 and 99.43 +/- 0.68 for RA and DO, respectively, in the HPTLC method. This method is simple, precise, and sensitive, and it is applicable for the simultaneous determination of RA and DO in pure powder and in capsule formulation.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Cromatografía en Capa Delgada/métodos , Domperidona/aislamiento & purificación , Cápsulas/química , Rabeprazol , Reproducibilidad de los Resultados , IncertidumbreRESUMEN
The semipreparative chiral separation of lansoprazole and two related compounds (pantoprazole and rabeprazole) using supercritical fluid chromatography (SFC) is presented in this work. Different loads were evaluated in order to obtain high enantiomeric purities and production rates. The volumes injected were 1, 2 and 4 mL. The concentrations of the racemic mixtures were 3 and 6 g/L for lansoprazole and 1.5 g/L for pantoprazole and rabeprazole. In all the cases, the recoveries, for a purity higher than 99.9%, were better for the second eluted enantiomer than for the first one. This fact conditioned the production rate of the first eluted enantiomer that, considering a fixed purity, was always lower than that obtained for the other one. In the case of lansoprazole it was possible to obtain 0.025 and 0.090 mg/min of the first and second eluted enantiomer, respectively, with an enantiomeric purity of 99.9%. For rabeprazole enantiomers 0.037 and 0.062 mg/min, and in the case of pantoprazole the results were better (0.062 and 0.122 mg/min) due to the higher resolution.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/análisis , Antiulcerosos/farmacología , Cromatografía con Fluido Supercrítico/métodos , 2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Fraccionamiento Químico , Técnicas de Química Analítica/métodos , Química Farmacéutica/métodos , Cromatografía/métodos , Diseño de Equipo , Lansoprazol , Modelos Químicos , Pantoprazol , Preparaciones Farmacéuticas/aislamiento & purificación , Rabeprazol , Estereoisomerismo , Factores de TiempoRESUMEN
A new and accurate HPLC method using sulfobutylether-beta-cyclodextrin (SBE-beta-CD) as chiral mobile phase additive (CMPA) was developed and validated for the determination of R-(+)pantoprazole in S-(-)pantoprazole. The influences of type and concentration of CD, ACN content and buffer pH of mobile phase on the resolution and retention of enantiomers were investigated. A baseline resolution of pantoprazole enantiomers was achieved on a Spherigel C18 column (150 mm x 4.6 mm, 5 microm) using ACN and 10 mM phosphate buffer (pH 2.5) containing 10 mM SBE-beta-CD (15:85 v/v) as mobile phase with a flow rate of 0.9 mL/min at 20 degrees C. The detection wavelength was set at 290 nm. The method was extensively validated in terms of accuracy, precision and linearity according to the International Conference on Harmonisation (ICH) guidelines and proved to be robust. The LOD and LOQ for R-(+)pantoprazole were 0.2 and 0.5 microg/mL, respectively, with 5 microL injection volume. A good linear relationship was obtained in the concentration range of 0.5-6.0 microg/mL with r(2) >0.999 for R-(+)pantoprazole. The percentage recovery of the R-(+)pantoprazole ranged from 92.1 to 101.2 in bulk drug of S-(-)pantoprazole. The method is capable of determining a minimum limit of 0.05% w/w of R-enantiomer in S-(-)pantoprazole bulk samples.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Antiulcerosos/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , beta-Ciclodextrinas/química , 2-Piridinilmetilsulfinilbencimidazoles/química , Antiulcerosos/química , Pantoprazol , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , EstereoisomerismoRESUMEN
This paper describes validated high-performance liquid chromatography (HPLC) and high-performance thin-layer chromatography (HPTLC) methods for the simultaneous estimation of pantoprazole (PANT) and domperidone (DOM) in pure powder and capsule formulations. The HPLC separation was achieved on a Phenomenex C18 column (250 mm id, 4.6 mm, 5 pm) using 0.01 M, 6.5 pH ammonium acetate buffer-methanol-acetonitrile (30 + 40 + 30, v/v/v, pH 7.20) as the mobile phase at a flow rate of 1.0 mL/min at ambient temperature. The HPTLC separation was achieved on an aluminum-backed layer of silica gel 60F254 using ethyl acetate-methanol (60 + 40, v/v) as the mobile phase. Quantification was achieved with ultraviolet (UV) detection at 287 nm over the concentration range 400-4000 and 300-3000 ng/mL with mean recovery of 99.35+/-0.80 and 99.08+/-0.57% for PANT and DOM, respectively (HPLC method). Quantification was achieved with UV detection at 287 nm over the concentration range 80-240 and 60-180 ng/spot with mean recovery of 98.40+/-0.67 and 98.75+/-0.71% for PANT and DOM, respectively (HPTLC method). These methods are simple, precise, and sensitive, and they are applicable for the simultaneous determination of PANT and DOM in pure powder and capsule formulations.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/análisis , Domperidona/análisis , Polvos/química , 2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Antiulcerosos/análisis , Antiulcerosos/aislamiento & purificación , Química Farmacéutica , Cromatografía Líquida de Alta Presión/métodos , Cromatografía Liquida/métodos , Cromatografía en Capa Delgada/métodos , Domperidona/aislamiento & purificación , Pantoprazol , Preparaciones Farmacéuticas/química , Sensibilidad y EspecificidadRESUMEN
This paper deals with multiple response simultaneous optimization using the Derringer's desirability function for the development of a reversed-phase HPLC method for the simultaneous determination of domperidone and pantoprazole in commercial pharmaceutical preparations. Twenty experiments, taking the retention factor of the first peak, the two resolutions, and three retention times as the responses with three important factors, mobile phase composition, buffer molarity and flow rate, were used to design mathematical models. The experimental responses were fitted into a second order polynomial and the six responses simultaneously optimized to predict the optimum conditions for the effective separation of the studied compounds. The optimum assay conditions were: methanol-acetonitrile-dipotassium hydrogen phosphate (pH 7.0; 15.3 mM) (20:33:47, v/v/v) as the mobile phase and at a flow rate of 1.19 ml/min. While using this optimum condition, baseline separation with a minimum resolution of 2.0 and a run time of less than 6 min were achieved. The method showed good agreement between the experimental data and predictive value throughout the studied parameter space. The optimized assay condition was validated according to ICH guidelines to confirm specificity, linearity, accuracy and precision.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Antiulcerosos/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Toma de Decisiones , Domperidona/aislamiento & purificación , Antagonistas de Dopamina/aislamiento & purificación , Proyectos de Investigación , 2-Piridinilmetilsulfinilbencimidazoles/química , Acetonitrilos/química , Análisis de Varianza , Antiulcerosos/química , Calibración , Cápsulas , Cromatografía Líquida de Alta Presión/instrumentación , Domperidona/química , Antagonistas de Dopamina/química , Metanol/química , Estructura Molecular , Pantoprazol , Fosfatos/química , Ácidos Fosfóricos/química , Compuestos de Potasio/química , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Comprimidos , Agua/químicaRESUMEN
Teicoplanin-bonded chiral stationary phase was prepared and used for the direct chiral separation of racemic pantoprazole sodium by reversed-phase high performance liquid chromatography (HPLC). The influences of organic modifiers, the composition of mobile phase, the flow rate and column temperature on enantioseparation were studied. It was found that methanol was preferred than acetonitrile when used as organic modifier. With the increase of column temperature, chiral solutes were less retained and the separation factor value decreased indicating that lower temperature was better for the enantioseparation. Better resolution was obtained at lower flow rates as a result of minimization of the resistance of mass transfer. Based on these experimental data, the chiral HPLC method for the analysis of pantoprazole sodium on prepared chiral column (150 mm x 4.6 mm i. d., 5 microm) was established with simplicity and good reproducibility, by using methanol-water (35 : 65, v/v) as mobile phase at a flow rate of 0.6 mL/min and 20 degrees C.
Asunto(s)
2-Piridinilmetilsulfinilbencimidazoles/aislamiento & purificación , Cromatografía Líquida de Alta Presión/métodos , Estereoisomerismo , Teicoplanina/química , Acetonitrilos/química , PantoprazolRESUMEN
By using the Kromasil CHI-TBB chiral stationary phase, the racemic mixture of pantoprazole sodium was resolved in the normal phase mode. The influences of the composition of the mobile phase, the content of acidic and basic additives and the flow rate on this enantiomer separation were studied. The chiral high performance liquid chromatographic method for the analysis of pantoprazole sodium was established with high efficiency and good repeatability, by using hexane-isopropanol-acetic acid mixture (95:5:0.1, v/v) as the mobile phase at a flow rate of 2.0 mL/min at 25 degrees C.