Dois métodos espectrofotométricos simples, sensíveis, seletivos e baratos são descritos para a determinação de sinvastatina (SMT) a granel e em comprimidos, utilizando permanganato como reagente oxidimétrico. No método A, a SMT é tratada com excesso conhecido de permanganato em meio de ácido acético e o oxidante que não reage é medido a 550 nm, enquanto no método B, a reação é efetuada em meio alcalino e o manganato resultante é medido a 610 nm. No método A, a quantidade de permanganato que reage corresponde ao conteúdo de SMT e a absorbância diminui linearmente com o aumento da concentração; no método B, a absorbância aumenta com o aumento da concentração. As condições de trabalho do ensaio foram otimizadas e os métodos, validados de acordo com as normas do ICH. Sob condições ótimas, a SMT pode ser ensaiada nas faixas de concentração de 1,47- 17,67x10-5 e de 2,27-27,18 x10-6 mol/L pelo método A e B, respectivamente. As absortividades molares calculadas são 2 x 10³ e 2,5 x 10(4) L/ mol/cm, respectivamente, para os métodos A e B, com os valores correspondentes de sensibilidade de Sandell de 0,0387 e 0,0178 μg/cm². Os limites de detecção (LOQ) também foram relatados. A exatidão e a precisão do ensaio foram determinadas pelo cálculo de três concentrações intra- e inter-dia; a RSD intra-dia foi <2% e a exatidão foi melhor que 2,15% (RE). Os métodos foram aplicados com sucesso à determinação de SMT em comprimidos com alta porcentagem de recuperação, boa exatidão e precisão e sem interferência mensurável dos excipientes. A exatidão foi posteriormente determinada no placebo e na mistura sintética e, também, pelo método de spike recovery.

Two simple, sensitive, selective and inexpensive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets using permanganate as the oxidimetric reagent. In method A, SMT is treated with a measured excess of permanganate in acetic acid medium and the unreacted oxidant is measured at 550 nm, whereas in method B the reaction is carried out in alkaline medium and the resulting manganate is measured at 610 nm. In method A, the amount of permanganate reacted corresponds to the SMT content and the absorbance is found to decrease linearly with the concentration; and in method B, the absorbance increases with concentration. The working conditions of assays were optimized, and the methods were validated according to the current ICH guidelines. Under optimum conditions, SMT could be assayed in the concentration ranges, 1.47 - 17.67x10-5 and 2.27 - 27.18 x10-6 mol/L by method A and method B, respectively. The calculated molar absorptivities are 3.2 x 10³ and 2.5 x 10(4) L/mol/cm for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0387 and 0.0178 μg/cm². The limits of detection (LOD) and quantification (LOQ) have also been reported. Accuracy and precision for the assay were determined by calculating the intra-day and inter-day at three concentrations; the intra-day RSD was < 2% and the accuracy was better than 2.15 % (RE). The methods were applied successfully for the determination of SMT in tablet dosage form with a high percentage of recovery, good accuracy and precision, and without measurable interference by the excipients. The accuracy was further ascertained from placebo and synthetic mixture analysis and also from the spike-recovery method.

Abstract Titrimetric and spectrophotometric assay of pantoprazole sodium (PPS) using permanganate as the oxidimetric reagent is described. In titrimetry, PPS is treated with a measured excess of permanganate in H2SO4 medium followed by the determination of unreacted oxidant by back titrating with a standard iron(II) solution. Spectrophotometry involves addition of a known excess of permanganate to PPS in H2SO4 medium followed by the measurement of absorbance of the residual permanganate at 545 nm. In both the methods, the amount of permanganate reacted corresponds to the PPS content. Experimental conditions that provide wide linear range, maximum sensitivity and selectivity, and accuracy and precisions have been optimized. In titrimetry, the calculations are based on a 1:1 (PPS : KMnO4) reaction stoichiometry and the method is applicable over 1.0-7.0 mg range. In spectrophotometry, Beer's law is obeyed over the concentration range 15.0-150.0 µg mL-1. The linear regression equation of the calibration graph is A = 0.78 + 0.005 C with a regression coefficient (r) of 0.9982 (n = 11). The apparent molar absorptivity is calculated to be 2.213 × 10³ l mol-1cm-1 and the Sandell sensitivity is 0.1954 µg cm-2. The limits of detection (LOD) and quantification (LOQ) calculated as per the ICH guidelines are 0.73 and 2.21 µg mL-1, respectively. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different levels of PPS; the intra-day and inter-day RSD was < 3.09 % and the accuracy was better than 3.5 %. The methods were successfully applied to the determination of PPS in three different brands of tablets with good accuracy and precision, and without detectable interference by excipients. The accuracy was further ascertained by placebo blank and synthetic mixture analyses and also by recovery experiments via standard-addition procedure.

En este trabajo se describe la cuantificación de pantoprazol sódico (PPS) mediante una valoración redox usando permanganato como agente oxidante siguiendo la determinación potenciométrica y espectrofotométricamente. En potenciometría, se adiciona un exceso de permanganato en medio H2SO4 y el PPS es cuantificado valorando el excedente de permanganato con una solución estándar de Fe(II). La determinación espectrofotométrica se realiza agregando permanganato a una concentración que asegure un exceso conocido y se mide la absorbancia del permanganato residual a 545 nm. En ambos métodos la cantidad de permanganato que reacciona con PPS esta relacionada con el contenido de PPS. Fueron optimizadas las condiciones experimentales que proporcionan un rango lineal, selectividad y sensibilidad máxima, precisión y exactitud. En potenciometría, los cálculos se basan en una estequiométrica de reacción 1:1 (PPS: KMnO4) y el método es aplicable en un intervalo de 1.0-7.0 mg. En espectrofotometría, la ley de Beer es lineal en un intervalo de concentración de 15.0-150.0 µg mL-1. La regresión lineal para la curva de calibración es A = 0.78 + 0.005 C con un coeficiente de regresión (r) de 0.9982 (n = 11). El coeficiente de absorbitividad molar calculado fue de 2.213 × 10³ l mol-1 cm-1 y la sensibilidad de Sandell de 0.1954 µg cm-2. Los límites de detección y cuantificación calculados de acuerdo con la guía ICH son 0.73 y 2.21 µg mL-1, respectivamente. La precisión y exactitud de los ensayos fueron determinadas calculando la variación intra-día e inter-día a tres niveles de PPS; la desviación estándar relativa intra-día e inter-día fue < 3.09 % y la exactitud fue mejor que 3.5 %. Los métodos fueron exitosamente aplicados para la determinación de PPS en tres diferentes marcas de tabletas con buena exactitud y precisión y sin interferencia detectable por los excipientes. La exactitud fue asegurada realizando el análisis de un placebo blanco y una muestra sintética y también por los experimentos de recuperación vía el procedimiento de adiciones estándar.

Three simple and sensitive spectrophotometric methods are described for the determination of simvastatin (SMT) in bulk drug and in tablets using bromate-bromide as the bromination reagent in acid medium, and three dyes as subsidiary reagents. All the three methods are based on the bromination of SMT by a known excess of in situ generated bromine followed by determination of unreacted bromine by reacting with a fixed amount of methyl orange (method A), indigo carmine (method B) or meta-cresol purple (method C) and measuring the absorbance at 510, 610 or 540 nm. In all the methods, the amount of bromine reacted corresponds to the amount of SMT. The experimental conditions for the assay have been optimized. In all the methods, the absorbance is found to increase linearly with the concentration of SMT at the respective wavelengths. Beer's law is obeyed over the ranges 0.5-3.0, 2.5-15.0 and 2.5-15.0 |ig mL-1 for method A, method B and method C, respectively and the respective molar absorptivity values are 1.0 ×10 5, 2.3 ×10(4) and 2.1 ×10(4) l mol-1 cm-1. The limits of detection and quantification are reported for all the methods. The performance of the methods was validated according to the present ICH guidelines. The methods gave similar results in terms of precision and accuracy. The repeatability and intermediate precision, expressed by the RSD was better than 2%. The accuracy of the methods expressed as relative error was satisfactory. The proposed methods were applied to the analysis of tablet form of SMT and the results tallied well with the label claim. No interference was observed from the concomitant substances normally added to tablets. The results were statistically compared with those of a literature method by applying the Student's t-test and F-test. The accuracy and validity of the methods were further ascertained by performing recovery studies via spike method and standard-addition method.

Se describen tres métodos espectrofotométricos simples y sensibles para la determinación de simvastatina (STM) en el medicamento a granel y en comprimidos usando bromato-bromuro como el reactivo de bromación en medio ácido, y tres colorantes como reactivos subsidiarios. Los tres métodos se basan en la bromación de STM por un exceso conocido de bromo generado in situ, seguida por la determinación del bromo que no reacciona, mediante una reacción con una cantidad fija de naranja de metilo (método A), carmín índigo (método B) o púrpura de metacresol (método C), y midiendo la absorbancia a 510, 610 o 540 nm. En todos los métodos, la cantidad de bromo que reacciona corresponde a la cantidad de STM. Las condiciones experimentales para la determinación fueron optimizadas. En todos los métodos, se encontró que la absorbancia se incrementa linealmente con la concentración de SMT a las respectivas longitudes de onda. La ley de Beer se cumple en los intervalos de 0.5-3.0, 2.5-15.0 y 2.5-15.0 mL-1 para el método A, el método B y el método C, respectivamente, y los valores de los respectivos coeficientes de absortividad molar son 1.0 ×10 5, 2.3 ×10(4) y 2.1 ×10(4) l mol-1 cm-1. Los límites de detección y cuantificación se reportan para cada método. El desempeño de los métodos se validó de acuerdo con los procedimientos actuales ICH. Los métodos dieron resultados semejantes en términos de precisión y exactitud. La repetibilidad y la precisión intermedia, expresadas por el RSD fueron mejor que el 2%. La exactitud de los métodos, expresada como error relativo, fue satisfactoria. Los métodos propuestos fueron aplicados satisfactoriamente al análisis de STM en comprimidos y los resultados correspondieron con lo reportado en el marbete. No se observaron interferencias de las substancias concomitantes normalmente añadidas a los comprimidos. Los resultados fueron estadísticamente comparados con otros métodos publicados en la literatura aplicando la prueba t y F de Student. La exactitud y la validez de los métodos fueron adicionalmente comprobadas a través de la realización de estudios de recuperación de muestras fortificadas y el método de adiciones patrón.

Two new simple, precise, rapid and extraction-free spectrophotometric methods are proposed for the determination of raloxifene hydrochloride (RLX) using bromate-bromide mixture and two dyes, methylene blue and rhodamine B, as reagents. The methods entail the addition of a known excess of bromate-bromide mixture to RLX in hydrochloric acid medium followed by determination of residual bromine by reacting with a fixed amount of either methylene blue and measuring the absorbance at 665 nm (Method A) or rhodamine B and measuring the absorbance at 555 nm (Method B). The amount of bromate reacted corresponds to the amount of RLX. In both the methods, the absorbance is found to increase linearly with the concentration of RLX. Under the optimum conditions, RLX could be assayed in the concentration ranges 0.5-5.0 and 0.1-2.0 µg mL-1 from method A and method B, respectively. The apparent molar absorptivities are calculated to be 7.0x10(4) and l.1x10(5) L mol-1cm-1 for method A and method B, respectively, and the corresponding Sandell sensitivity valúes are 0.0073 and 0.0048 µg cm-2. The limits of detection and quantification have also been reported for both the spectrophotometric methods. The overall reproducibility of the methods was excellent and recoveries were 98.3-102.5% and 98.2-103.2% for method A and method B, respectively. The proposed methods can be readily utilized for bulk drug and in pharmaceutical formulations

A new high performance liquid chromatographic (HPLC) method in reverse phase was developed and validated for the determination of olanzapine (OLZ) in pharmaceutical formulations. Optimum separation was achieved in less than 10 min using a reversed phase Intersil ODS column (150 mm × 4.6 mm, i.d., particle size 5 µm), and elution was accomplished using a mobile phase (0.5 mL/min). Detection was carried out using a UV detector set at 271 nm. A rectilinear relationship between mean peak area and concentration of OLZ was observed in the range 10-200 µg/mL, with a detection limit of 3.0 µg/mL and a quantization limit of 8.0 µg/mL. Intra-day and Inter-day precision, and accuracy of the methods have been established according to the current ICH guidelines. The developed method was successfully applied to the determination of OLZ in pharmaceutical formulations. The results were statistically compared with those of the reference method by applying Student's t-test and F-test. Accuracy, evaluated by means of the spike recovery method, was in the range 97.7-102.3%, with precision (RSD) better than 2%. No interference was observed from the coformulated substances. The method was economical in terms of the time taken and the amount of solvent used.

Se describe un nuevo método de cromatografía de alta resolución (HPLC) en fase inversa para la determinación de olanzapina (OLZ) en formulación de medicamentos, lográndose también su validación. La separación óptima se logró en menos de 10 min, utilizando una columna de fase inversa Intersil ODS (150 mm × 4.6 mm, d.i., y 5 µm en tamaño de partícula), y con una elusión de fase móvil de 0.5 mL/min. La detección se llevó a cabo empleando un detector UV a una longitud de onda de 271 nm. Se observó una relación lineal entre el área media del pico y la concentración de OLZ en el intervalo de 10-200 µg/mL, con un límite de detección de 3.0 µg/mL y un límite de cuantificación de 8.0 µg/mL. La precisión media y exactitud de los métodos se establecieron de acuerdo a los manuales actualizados ICH. El método desarrollado se aplicó exitosamente para la determinación de OLZ en formulaciones farmacéuticas. Los resultados se compararon estadísticamente con aquéllos del método de referencia, mediante la aplicación de las pruebas t y F del método Student. La exactitud, la cual es evaluada mediante el método de recobro de pico, alcanzó un intervalo de 97.7-102.3%, con una precisión (RSD) mejor que 2%. No se observó interferencia de las sustancias de la formulación. En cuanto al aspecto económico, el método fue ventajoso en términos del tiempo de determinación y la cantidad del disolvente empleado.