Application of redox reactions for the determination of valganciclovir hydrochloride in pharmaceuticals

Two simple, selective and sensitive spectrophotometric methods were developed and validated for the determination of valganciclovir hydrochloride (VLGH) in pure drug and tablets. The first method was based on the reduction of iron(III) to iron(II) by VLGH and subsequent formation of iron(III)-ferricyanide complex (Prussian blue) in acid medium which was measured at 730 nm (method A). In the second method (method B), permanganate was reduced by VLGH to bluish green manganate in alkaline medium and the absorbance was measured at 610 nm. The absorbance measured in each case was related to VLGH concentration. The experimental conditions were carefully studied and optimized. Beer's law was obeyed over the concentration ranges of 2.5-20.0 and 2.0-40.0 µg mL-1 for method A and method B, respectively, with corresponding molar absorptivity values of 1.28×104 and 6.88×103 L mol-1 cm-1. The limits of detection (LOD) and quantification (LOQ) were 0.11 and 0.33 µg mL-1 (method A) and 0.21 and 0.64 µg mL-1 (method B). Within-day and between-day relative standard deviations (%RSD) at three different concentrations levels were < 2.4%, and the respective relative errors (%RE) were ≤ 3%. The proposed methods were successfully applied to the determination of VLGH in tablets, and the results confirmed that the proposed methods were equally precise and accurate as the official method.

Application of Cerium (IV) as an Oxidimetric Agent for the Determination of Ethionamide in Pharmaceutical Formulations.

Two simple methods are described for the determination of ethionamide (ETM) in bulk drug and tablets using cerium (IV) sulphate as the oxidimetric agent. In both methods, the sample solution is treated with a measured excess of cerium (IV) solution in H2SO4 medium, and after a fixed standing time, the residual oxidant is determined either by back titration with standard iron (II) solution to a ferroin end point in titrimetry or by reacting with o-dianisidine followed by measurement of the absorbance of the orange-red coloured product at 470 nm in spectrophotometry. In titrimetry, the reaction proceeded with a stoichiometry of 1 : 2 (ETM : Ce (IV)) and the amount of cerium (IV) consumed by ETM was related to the latter's amount, and the method was applicable over 1.0-8.0 mg of drug. In spectrophotometry, Beer's law was obeyed over the concentration range of 0.5-5.0 µg/mL ETM with a molar absorptivity value of 2.66 × 104 L/(mol·cm). The limits of detection (LOD) and quantification (LOQ) calculated according to ICH guidelines were 0.013 and 0.043 µg/mL, respectively. The proposed titrimetric and spectrophotometric methods were found to yield reliable results when applied to bulk drug and tablets analysis, and hence they can be applied in quality control laboratories.

RAPID SPECTROPHOTOMETRIC DETERMINATION OF TRIFLUOPERAZINE DIHYDROCHLORIDE AS BASE FORM IN PHARMACEUTICAL FORMULATION THROUGH CHARGE-TRANSFER COMPLEXATION.

Two simple and selective spectrophotometric methods are described for the determination of trifluoperazine dihydrochloride (TFH) as base form (TFP) in bulk drug, and in tablets. The methods are based on the molecular charge-transfer complexation of trifluoperazine base (TFP) with either 2,4,6-trinitrophenol (picric acid; PA) or 2,4-dinitrophenol (DNP). The yellow colored radical anions formed are quantified at 410 run (PA method) or 415 nm (DNP method). The assay conditions were optimized for both the methods. Beer's law is obeyed over the concentration ranges of 1.5-24.0 pg/mL in PA method and 5.0-80.0 µg/mL in DNP method, with respective molar absorptivity values of 1.03 x 10(4) and 6.91 x 10(3) L mol-1 cm-1. The reaction stoichiometry in both methods was evaluated by Job's method of continuous variations and was found to be 1 : 2 (TFP : PA, TFP : DNP). The developed methods were successfully applied to the determination of TFP in pure form and commercial tablets with good accuracy and precision. Statistical comparison of the results was performed using Student's t-test and F-ratio at 95% confidence level and the results showed no significant difference between the reference and proposed methods with regard to accuracy and precision. Further, the accuracy and reliability of the methods were confirmed by recovery studies via standard addition technique.

INVESTIGATION AND OPTIMIZATION OF TITRIMETRIC AND SPECTROPHOTOMETRIC METHODS FOR THE ASSAY OF FLUNARIZINE DIHYDROCHLORIDE USING IN SITU BROMINE.

Three indirect methods for the assay of flunarizine dihydrochloride (FNH) in bulk drug and commercial formulation based on titrimetric and spectrophotometric techniques using bromate-bromide mixture are described. In titrimetry, a measured excess of bromate-bromide mixture is added to an acidified solution of FNH and the unreacted bromine is determined iodometrically (method A). Spectrophotometry involves the addition of a known excess of bromate-bromide mixture to FNH in acid medium followed by estimation of unreacted bromine by its reaction with excess iodide and the liberated iodine (I3⁻) is either measured at 370 nm (method B) or liberated iodine reacted with starch followed by the measurement of the blue colored starch-iodide complex at 575 run (method C). Titrimetric method is applicable over the range 4.5-30.0 mg FNH (method A), and the reaction stoichiometry is found to be 1:2 (FNH:KBrO3). The spectrophotometric methods are applicable over the concentration ranges 0.8-16.0 µg/mL and 0.4-8.0 µg/mL FNH for method B and method C, respectively. The molar absorptivities are calculated to be 2.83 x 104 and 4.96 x 104 L mol⁻¹cm⁻¹ for method B and method C, respectively, and the corresponding Sandell sensitivity values are 0.0168 and 0.0096 µg cm⁻². The proposed methods have been applied successfully for the determination of FNH in pure form and in its dosage form and the results were compared with those of a literature method by applying the Student's t-test and F-test.

Titrimetric and spectrophotometric assay of diethylcarbamazine citrate in formulations using iodate and iodide mixture as reagents

One titrimetric and two spectrophotometric methods are proposed for the determination of diethylcarbamazine citrate (DEC) in bulk drug and in formulations using potassium iodate and potassium iodide as reagent. The methods employ the well-known analytical reaction between iodate and iodide in the presence of acid. In titrimetry (method A), the drug was treated with a measured excess of thiosulfate in the presence of unmeasured excess of iodate-iodide mixture and after a standing time of 10 min, the surplus thiosulfate was determined by back titration with iodine towards starch end point. Titrimetric assay is based on a 1:3 reaction stoichiometry between DEC and iodine and the method is applicable over 2.0-10.0 mg range. The liberated iodine is measured spectrophotometrically at 370 nm (method B) or the iodine-starch complex measured at 570 nm (method C). In both methods, the absorbance is found to be linearly dependent on the concentration of iodine, which in turn is related to DEC concentration. The calibration curves are linear over 2.5-50 and 2.5-30 µg mL-1 DEC for method B and method C, respectively. The calculated molar absorptivity and Sandell sensitivity values were 6.48×103 L mol-1 cm-1 and 0.0604 µg cm-2, respectively, for method B, and their respective values for method C are 9.96×103 L mol-1 cm-1 and 0.0393 µg cm-2. The intra-day and inter-day accuracy and precision studies were carried out according to the ICH guidelines. The methods were successfully applied to the analysis of DEC formulations.

Propõem-se titulação e dois métodos espectrofotométricos para a determinação de citrato de dietilcarbamazina (DEC) a granel e em suas formulações, usando iodato de potássio e iodeto de potássio como reagente. Os métodos utilizam a reação analítica conhecida entre iodato e iodeto, na presença de ácido. Na titulometria (Método A), o fármaco foi tratado com excesso medido de tiossulfato, na presença de excesso não medido de mistura iodato-iodeto e, depois de um tempo de repouso de 10 min, o excesso de tiossulfato foi determinado por titulação de retorno com iodo até o ponto final com amido. A titulação é baseada em reação com estequiometria 1:3 entre DEC e iodo e o método é aplicável na faixa de 2.0-10.0 mg. O iodo liberado é medido espectrofotometricamente a 370 nm (método B) ou o complexo de iodo-amido medido a 570 nm (método C). Em ambos os métodos, a absorvância é considerada linearmente dependente da concentração de iodo, a qual, por sua vez, está relacionada à concentração de DEC. As curvas de calibração são lineares para concentrações de DEC de 2.5-50 e 2.5-30 mg mL- 1 para o método B e para o método C, respectivamente. A absortividade molar calculada e os valores de sensibilidade Sandel foram 6.48×103 L mol-1 cm- 1 e 0.0604 ug cm-2, respectivamente, para o método B, e os seus respectivos valores para o método C são 9.96×103 L mol-1 cm-1 e 0.0393 mg cm-2. Os estudos de exatidão e precisão intra-dia e inter-dia foram realizados de acordo com as diretrizes da ICH. Os métodos foram aplicados com sucesso na análise de formulações de DEC.

Simple and rapid spectrophotometric assay of albendazole in pharmaceuticals using iodine and picric acid as CT complexing agents

Two simple, rapid and inexpensive spectrophotometric methods are described for the determination of albendazole (ALB) in bulk drug and in tablets. The methods are based on charge-transfer (CT) complexation reaction involving ALB as n-donor and iodine as σ-acceptor (method A) in dichloromethane or picric acid (PA) as π-acceptor (method B) in chloroform. The absorbance of CT complexes was measured at 380 nm for method A, and 415 nm for method B. The optimization of the experimental conditions is described. Under optimum conditions, Beer's law obeyed over the concentration ranges 8.0-240 and 2.4-42 μg mL-1 for method A and method B, respectively. The apparent molar absorptivity of CT complexes at the respective λmax are calculated to be 1.17×103 and 5.22×103 L mol-1 cm-1 respectively, and the corresponding Sandell sensitivity values are 0.2273 and 0.0509 ng cm-2. The limits of detection (LOD) and quantification (LOQ) are calculated to be (0.69 and 2.08), and (0.10 and 0.30) μg mL-1 with method A, and method B, respectively. The intra-day and inter-day accuracy expressed as % RE and precision expressed as % RSD were less than 3%. The methods were applied to the determination of ALB in tablets.

Dois métodos espectrofotométricos, simples, rápidos e de baixo custo são descritos para a determinação do albendazol (ALB) como fármaco e em comprimidos. Os métodos baseiam-se em reação de complexação de transferência de carga (TC) envolvendo ALB como n-doador e iodo como aceptor de σ (método A) em diclorometano ou ácido pícrico como π-aceptor (método B), em clorofórmio. A absorção de complexos TC foi medida em 380 nm para o método A e 415 nm para o método B. A otimização das condições experimentais é descrita. Sob condições ideais, a lei de Beer é obedecida nas concentrações entre 8,0 e 240 e 2,4 e 42 μg mL-1 para os métodos A e B, respectivamente. A absortividade molar aparente dos complexos de TC no respectivo λ max foi calculada como sendo 1,17×103 e 5,22×103 L mol-1 cm-1, respectivamente, e os valores de sensibilidade de Sandell correspondentes são 0,2273 e 0,0509 ng cm-2. Os limites de detecção (LOD) e quantificação (LOQ) calculados são (0,69 e 2,08) e (0,10 e 0,30) μg mL-1, com o método A e o método B, respectivamente. A exatidão intra-dia e inter-dia, expressa como % de erro relativo e precisão expressa como % DPR foi inferior a 3%. Os métodos foram aplicados para a determinação de ALB em comprimidos.

Titrimetric and Spectrophotometric Methods for the Assay of Ketotifen Using Cerium(IV) and Two Reagents.

One titrimetric and two spectrophotometric methods are described for the determination of ketotifen fumarate (KTF) in bulk drug and in tablets using cerium(IV) as the oxidimetric agent. In titrimetry (method A), the drug was treated with a measured excess of cerium(IV) in H2SO4 medium and after a standing time of 10 min, the surplus oxidant was determined by back titration with iron(II). The spectrophotometric procedures involve addition of a known excess of cerium(IV) to KTF in acid medium followed by the determination of unreacted oxidant by reacting with either p-dimethyl amino benzaldehyde and measuring the resulting colour at 460 nm (method B) or o-dianisidine and subsequent measurement of the absorbance of coloured product at 470 nm (method C). Titrimetric assay is based on a 1 : 2 reaction stoichiometry between KTF and cerium(IV) and the method is applicable over 2-18 mg range. In spectrophotometry, regression analysis of Beer's law plots showed a good correlation in 0.4-8.0 and 0.4-10.0 g mL(-1) KTF ranges for method B and method C, respectively, and the corresponding molar absorptivity coefficients are calculated to be 4.0 × 10(4) and 3.7 × 10(4) L mol(-1) cm(-1).

Utilization of N-bromosuccinimide as a brominating agent for the determination of sumatriptan succinate in bulk drug and tablets.

One titrimetric and two spectrophotometric methods which are simple, sensitive, and economic are described for the determination of sumatriptan succinate (STS) in bulk drug and in tablet dosage form using N-bromosuccinimide (NBS) as a brominating agent. In titrimetry, aqueous solution of STS is treated with a measured excess of NBS in acetic acid medium, and after the bromination of STS is judged to be complete, the unreacted NBS is determined iodometrically (method A). Spectrophotometric methods entail addition of a known excess of NBS in acid medium followed by the determination of residual NBS by its reaction with excess iodide, and the liberated iodine (I3 (-)) is either measured at 370 nm (method B) or liberated iodine is reacted with starch followed by the measurement of the blue colored starch-iodine complex at 570 nm (method C). Titrimetric method is applicable over range 1.0-10.0 mg STS (method A), and the reaction stoichiometry is found to be 1 : 3 (STS : NBS). The spectrophotometric methods obey Beer's law for concentration range 0.6-15.0 µ g mL(-1) (method B) and 0.2-4.0 µ g mL(-1) (method C). The calculated apparent molar absorptivity values were found to be 2.10 × 10(4) and 7.44 × 10(4) L mol(-1) cm(-1), for method B and method C, respectively.

Sensitive spectrophotometric determination of atenolol in pharmaceutical formulations using bromate-bromide mixture as an eco-friendly brominating agent.

Three simple and sensitive spectrophotometric methods are proposed for the determination of atenolol (ATN) in bulk drug and tablets. The methods are based on the bromination of ATN by the bromine generated in situ by the action of the acid on the bromate-bromide mixture followed by the determination of unreacted bromine by reacting with a fixed amount of either meta-cresol purple (MCP) and measuring the absorbance at 540 nm (method A) and 445 nm (method B) or erioglaucine (EGC) and measuring the absorbance at 630 nm (method C). Beer's law is valid within the concentration ranges of 1.0-20.0, 2.0-40.0 and 1.0-8.0 µg/mL for method A, method B and method C, respectively. The calculated molar absorptivities were found to be 1.20×10(4), 4.51×10(3) and 3.46 × 10(4) L/mol · cm for method A, method B and method C, respectively. Sandell's sensitivity values, correlation coefficients, limits of detection and quantification are also reported. Recovery results were statistically compared with those of a reference method by applying Student's t- and F-test. The novelty of the present study is the measurement of two different colors using MCP, that is, red-pink color of MCP in acid medium at 540 nm and yellowish-orange color of brominated MCP at 445 nm.

Simple, sensitive and selective spectrophotometric methods for the determination of atenolol in pharmaceuticals through charge transfer complex formation reaction.

Three rapid, selective and sensitive spectrophotometric methods have been proposed for the quantitative determination of atenolol (ATN) in pure form as well as in its pharmaceutical formulation. The methods are based on charge transfer complexation reaction of ATN as n-electron donor with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), 2,4-dinitrophenol (DNP) and 2,4,6-trinitrophenol (picric acid; PA) as pi-acceptors to give highly colored radical anion species. The colored products were quantified spectrophotometrically at 590 nm with DDQ (method A) and at 420 nm with both DNP (method B) and PA (method C). Under the optimized experimental conditions, Beer's law is obeyed over the concentration ranges of 3-48, 2-24 and 1.5-18 µg/mL ATN for method A, method B and method C, respectively. The molar absorptivity, Sandell sensitivity, limits of detection and quantification are also reported. The effects of reaction medium, reaction time and reagent concentration on the sensitivity and stability of the complexes formed have been examined. The proposed methods were successfully applied to the determination of ATN in pure form and commercial tablets with good accuracy and precision. Statistical comparison of the results was performed using Student's t-test and F-ratio at 95% confidence level and the results showed no significant difference between the reference and proposed methods with regard to accuracy and precision. Further, the accuracy and reliability of the methods were confirmed by recovery studies via standard addition technique.

Application of ion-pair complexation reaction for the spectrophotometric determination of bupropion hydrochloride in pharmaceuticals.

This is the first report on the use of visible spectrophotometry for the determination of bupropion hydrochloride (BUPH), a second-generation antidepressant, in pharmaceuticals. Two sensitive, selective, and cost-effective spectrophotometric methods are described. The first method (method A) is based on the formation of yellow-coloured ion-pair complex between the BUPH and methyl orange (MO) at pH 3.80 ± 0.10 which was extracted into dichloromethane and the absorbance measured at 425 nm. The second method (method B) is based on the breaking of the yellow BUPH-MO ion-pair complex in acid medium followed by the measurement of the red-pink colour at 520 nm. Beer's Law is obeyed over the concentration ranges of 1.00-12.0 and 0.48-7.20 µg ml(-1) BUPH for method A and method B, respectively. The molar absorptivities are calculated to be 2.18 × 10(4) and 3.79 × 10(4) l mol(-1) cm(-1) for method A and method B, respectively, and the corresponding Sandell sensitivity values are 0.0127 and 0.0073 µg cm(-2) . The limits of detection and quantification have also been reported. The proposed methods were applied successfully to the determination of BUPH in pure drug and commercial tablets. The accuracy and reliability of the proposed methods were further ascertained by recovery studies via standard addition technique.

Use of two sulfonthalein dyes in the extraction-free spectrophotometric assay of tramadol in dosage forms and in spiked human urine based on ion-pair reaction.

Tramadol is a centrally acting analgesic used in the prevention and treatment of moderate to severe pain. Two sensitive, selective, and rapid spectrophotometric methods are described for the determination of tramadol in its dosage forms and in spiked human urine. The methods are based on formation of yellow ion-pairs between tramadol and two sulfonthalein dyes; bromocresol purple (BCP) and bromocresol green (BCG) in dichloromethane medium followed by absorbance measurement at 400 and 410 nm, respectively. Under the optimum conditions, tramadol could be assayed in the concentration ranges, 1-15 and 1-16 µg ml(-1) with correlation coefficient greater than 0.999 in both cases. The molar absorptivity values are calculated to be 1.84 × 10(4) and 1.97 × 10(4) l mol(-1) cm(-1) for BCP and BCG methods, respectively; and the corresponding Sandell sensitivity values are 0.0143 and 0.0134 µg cm(-2). The limits of detection (LOD) and quantification (LOQ) have also been reported. The stoichiometry of the reaction was found to be 1:1 in both cases and the conditional stability constant (K(f)) values of the ion pairs have been calculated. The within-day and between-day RSD were 0.9-1.96% and 1.56-3.21%, respectively. The methods were successfully applied to the determination of tramadol in tablets and injections and also in spiked human urine with good recoveries. The procedures are simple, accurate, and suitable for quality control application.

Titrimetric and spectrophotometric assay of oxcarbazepine in pharmaceuticals using N-bromosuccinimide and bromopyrogallol red.

Titrimetric and spectrophotometric methods are described for the determination of oxcarbazepine (OXC) in bulk drug and in tablets. The methods use N-bromosuccinimide (NBS) and bromopyrogallol red (BPR) as reagents. In titrimetry (method A), an acidified solution of OXC is titrated directly with NBS using methyl orange as indicator. Spectrophotometry (method B) involves the addition of known excess of NBS to an acidified solution of OXC followed by the determination of the unreacted NBS by reacting with BPR and measuring the absorbance of the unreacted dye at 460 nm. Titrimetry allows the determination of 6-18 mg of OXC and follows a reaction stoichiometry of 1 : 1 (OXC : NBS), whereas spectrophotometry is applicable over the concentration range of 0.8-8.0 µg mL(-1). Method B with a calculated molar absorptivity of 2.52 × 10(4) L mol(-1) cm(-1) is the most sensitive spectrophotometric method ever developed for OXC. The optical characteristics such as limits of detection (LOD), quantification (LOQ), and Sandell's sensitivity values are also reported for the spectrophotometric method. The accuracy and precision of the methods were studied on intraday and interday basis. The methods described could usefully be applied to routine quality control of tablets containing OXC. No interference was observed from common pharmaceutical adjuvants. Statistical comparison of the results with a reference method shows an excellent agreement and indicates no significant difference in accuracy and precision. The reliability of the methods was further ascertained by recovery studies in standard addition procedure.

Sensitive and selective spectrophotometric determination of gabapentin in capsules using two nitrophenols as chromogenic agents.

Two simple and selective spectrophotometric methods have been proposed for the determination of gabapentin (GBP) in pure form and in capsules. Both methods are based on the proton transfer from the Lewis acid such as 2,4,6-trinitrophenol (picric acid; PA) or 2,4-dinitrophenol (2,4-DNP) to the primary amino group of GBP which works as Lewis base and formation of yellow ion-pair complexes. The ion-pair complexes formed show absorption maximum at 415 and 420 nm for PA and 2,4-DNP, respectively. Under the optimized experimental conditions, Beer's law is obeyed over the concentration ranges of 1.25-15.0 and 2.0-18.0 µg mL(-1) GBP for PA and 2,4-DNP methods, respectively. The molar absorptivity, Sandell's sensitivity, detection and, quantification limits for both methods are also reported. The proposed methods were applied successfully to the determination of GBP in pure form and commercial capsules. Statistical comparison of the results was performed using Student's t-test and F-ratio at 95% confidence level, and there was no significant difference between the reference and proposed methods with regard to accuracy and precision. Further, the validity of the proposed methods was confirmed by recovery studies via standard addition technique.

Rapid titrimetric and spectrophotometric determination of ofloxacin in pharmaceuticals using N-bromosuccinimide / Determinação titulométrico e espectrofotométrico rápido de ofloxacina em produtos farmacêuticos usando N -bromosuccinimida

One titrimetric and two spectrophotometric methods have been described for the determination of ofloxacin (OFX) in bulk drug and in tablets, employing N-Bromosuccinimide as an analytical reagent. The proposed methods involve the addition of a known excess of NBS to OFX in acid medium, followed by determination of unreacted NBS. In titrimetry, the unreacted NBS is determined iodometrically, and in spectrophotometry, unreacted NBS is determined by reacting with a fixed amount of either indigo carmine (Method A) or metanil yellow (Method B). In all the methods, the amount of NBS reacted corresponds to the amount of OFX. Titrimetry allows the determination of 1-8 mg of OFX and the calculations are based on a 1:5 (OFX:NBS) reaction stoichiometry. In spectrophotometry, Beer's law is obeyed in the concentration ranges 0.5-5.0 µg/mL for method A and 0.3-3.0 µg/mL for method B. The molar absorptivities are calculated to be 5.53x10(4) and 9.24x10(4) L/mol/cm for method A and method B, respectively. The methods developed were applied to the assay of OFX in tablets, and results compared statistically with those of a reference method. The accuracy and reliability of the methods were further ascertained by performing recovery tests via the standard-addition method.

Descrevem-se métodos, um titulométrico e dois espectrofotométricos, para a determinação de ofloxacino (OFX) na matéria-prima e em comprimidos, empregando a N-bromossuccinimida (NBS) como reagente analítico. Os métodos propostos envolvem a adição de excesso conhecido de NBS ao OFX, em meio ácido, seguida de determinação do NBS que não reagiu. Na titulometria, o NBS que não reagiu é determinado iodometricamente e na espectrofotometria, o NBS que não reagiu é determinado pela reação com quantidade fixa de índigo carmim (Método A) ou amarelo de metanila (Método B). Em todos os métodos, a quantidade de NBS que reagiu corresponde à quantidade de OFX. A titulometria permite a determinação de 1-8 mg de OFX e os cálculos se baseiam na estequiometria de reação de 1:5 (OFX:NBS). Na espectrofotometria, a Lei de Beer é obedecida nas faixas de concentração de 0,5-5,0 µg/mL, para o método A, e de 0,3-3,0 µg/mL, para o método B, respectivamente. Os métodos desenvolvidos foram aplicados para o teste de OFX em comprimidos e os resultados foram comparados estatisticamente com aqueles do método de referência. A precisão e a confiabilidade dos métodos foram, posteriormente, verificadas por meio dos testes de recuperação via método de adição de padrão.

Sensitive and selective spectrophotometric assay of gabapentin in capsules using sodium 1, 2-naphthoquinone-4-sulfonate.

A simple, sensitive, and selective spectrophotometric method has been developed for the determination of gabapentin (GBP) in capsules. The method is based on the reaction of GBP and sodium 1,2-naphthoquinone-4-sulfonate (NQS) in the presence of Clark and Lubs buffer of pH 11 to form an orange-coloured product which was measured at 495 nm. The parameters that affect the reaction were carefully optimized and under the optimized conditions, linear relationship was obtained in the concentration range of 7.5-75 µg ml(-1) GBP. The molar absorptivity, limits of detection (LOD) and quantification (LOQ) and Sandell sensitivity are also reported. The proposed method was successfully applied to the determination of GBP in capsules with good accuracy and precision and without detectable interference from common excipients. The reliability of the proposed method was further established by parallel determination by the reference method and also by recovery studies. The reaction mechanism is proposed and discussed.

Volumetric and spectrophotometric determination of oxcarbazepine in tablets.

Two cerimetric procedures are described for the assay of oxcarbazepine (OXC) in bulk drug and in tablets. Titrimetry (method A) is based on the reaction of OXC by a measured excess cerium(IV) sulphate in sulphuric acid medium and the determination of the unreacted oxidant by titration with iron(II) solution using ferroin as indicator. Spectrophotometry (method B) is based on oxidation of OXC by cerium(IV) in perchloric acid (HClO4) medium and the determination of the unreacted oxidant using a colour reaction with p-dimethylaminobenzaldehyde (p-DMAB) having an absorption maximum of 460 nm. The titrimetric method is applicable in the range of 2.0-20.0 mg OXC with a 1:2 reaction stoichiometry [OXC:Ce(IV)]. In the spectrophotometric method a rectilinear relationship is obtained over the concentration range of 0.3-6.0 µg mL-1 OXC. The linear regression equation of the calibration graph is A = 0.9820-0.1477 C with a regression coefficient (r) of -0.9967 (n = 6). The molar absorptivity is calculated to be 3.76 × 104 L mol-1 cm-1 and the Sandell sensitivity is 0.0067 µg cm-2. The limits of detection (LOD) and quantification (LOQ) values are calculated according to ICH guidelines. The methods are successfully applied to the determination of OXC in tablets.

Sensitive and selective spectrophotometric assay of doxycycline hyclate in pharmaceuticals using Folin-Ciocalteu reagent.

A spectrophotometric method for the determination of doxycycline (DOX) is described. The method is based on the formation of blue colored chromogen due to reduction of tungstate and/or molybdate in Folin-Ciocalteu (F-C) reagent by DOX in alkaline medium. The colored species has an absorption maximum at 770 nm and the system obeys Beer's law over the concentration range 0.75-12.0 µg mL-1 DOX. The apparent molar absorptivity is 2.78 × 104 L mol-1 cm-1. The limit of quantification and detection values are reported to be 0.20 and 0.08 µg mL-1, respectively. Over the linear range applicable, the accuracy and precision of the method were evaluated on intra-day and inter-day basis. The reported mean accuracy value was 101.0 ± 1.7 %, the relative error was ≤ 2.7 % and the relative standard deviation was ≤ 2.5 %. Application of the proposed method to bulk powder and commercial pharmaceutical tablets is also presented. No significant difference was obtained between the results of the proposed method and the official BP method. The procedure described in this paper is simple, rapid, accurate and precise.

Spectrophotometric determination of isoxsuprine hydrochloride using 3-methyl-2-benzothiazolinone hydrazone hydrochloride in spiked human urine and pharmaceuticals.

Two selective and sensitive spectrophotometric methods are proposed for the determination of isoxsuprine hydrochloride (ISX) in spiked human urine and in pharmaceuticals. The methods are based on the oxidative-coupling reaction between 3-methyl-2-benzothiazolinone hydrazone hydrochloride (MBTH) and ISX in the presence of Ce(SO(4))(2). The novelty of the proposed reaction is the formation of two different colored chromogens at two different pHs. The resulting product at pH<1.5 is a red colored chromogen peaking at 500nm (method A) and that formed between the pH 3.85 and 4.15, is violet colored with an absorption maximum at 580nm (method B). In both the methods, absorbance of the chromogen is found to increase linearly with the concentration of ISX as is corroborated by the correlation coefficients of 0.9989 and 0.9970, and the systems obey Beer's law over the ranges of 1.4-21.0 and 1.0-15.0microgml(-1), for method A and method B, respectively. The calculated molar absorptivities are 1.08 x 10(4) and 1.78 x 10(4)lmol(-1)cm(-1) for method A and method B, respectively with corresponding Sandell sensitivity values of 0.0311 and 0.0190microgcm(-2). The reaction stoichiometry, in both the methods, was evaluated by the limiting logarithmic method and was found to be 1:1 (ISX:MBTH). The methods were successfully applied to the determination of ISX in spiked human urine and pharmaceutical formulation.

Sensitive spectrophotometric assay of simvastatin in pharmaceuticals using permanganate / Ensaio espectrofotométrico sensíveis de sinvastatina em medicamentos utilizando permanganato

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 percent and the accuracy was better than 2.15 percent (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.

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 por cento e a exatidão foi melhor que 2,15 por cento (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.