Nagaraju Rajendraprasad

Highly sensitive spectrophotometric determination of olanzapine using cerium(IV) and iron(II) complexes of 1,10-phenanthroline and 2,2′-bipyridyl

Two highly sensitive spectrophotometric methods have been developed for the determination of olanzapine (OLP) in pharmaceuticals using cerium(IV) and iron(II) complexes of 1,10-phenanthroline and 2,2′-bipyridyl as reagents. The methods are based on the oxidation of OLP in acidic medium by a known excess of cerium(IV) followed by the determination of the unreacted oxidant by reacting with either ferroin and measuring the absorbance at 510 nm (method A) or iron(II)-2,2′-bipyridyl complex and measuring the absorbance at 525 nm (method B). The amount of cerium(IV) reacted corresponds to the amount of OLP. In both the methods, the absorbance is found to increase linearly with OLP concentration as shown by the correlation coefficient (r) of 0.9980 and 0.9958 for method A and method B, respectively. The calibration graphs are linear over the concentration range of 0.2–2.0 μg/mL in both the methods. The calculated molar absorptivity values are 1.00 × 106 and 7.03 × 105 L/mol cm, for method A and method B. The LOD and LOQ values for method A are calculated to be 0.04 and 0.13 μg/mL and the values are 0.07 and 0.22 μg/mL for method B, respectively. The methods were validated as per the current ICH guidelines. Both the methods gave similar results in terms of accuracy and precision. The RSD was less than 3% and the accuracy, obtained from recovery experiments, was 98.76–101.4%. The methods developed were applied to the determination of OLP in tablets and results agreed well with the label claim.

Determination of olanzapine by spectrophotometry using permanganate

Dois metodos espectrofotometricos novos, usando o permanganato como o reagente oxidimetrico para a determinacao da olanzapina (OLP) foram utilizados e validados de acordo com as diretrizes atuais do ICH. Os metodos envolveram a adicao de excesso conhecido de permanganato a OLP em meio acido ou alcalino, determinando-se o permanganato que nao reagiu em 550 nm (metodo A), ou pela cor verde-azulada do manganato a 610 nm (metodo B). A diminuicao da absorbância no metodo A ou o aumento da absorbância no metodo B, em funcao da concentracao de OLP, foi medida e relacionada a concentracao de OLP. Sob condicoes otimizadas, a lei de Beer foi obedecida, nas faixas de concentracao de 2,0 a 20 e 1,0 a 10 ao μg mL-1, no metodo A e no metodo B, respectivamente. Os valores de absortividade molar foram de 1,34 x 104 e 2,54 x 104 l mol-1cm-1 para o metodo A e para o metodo B, respectivamente, e as sensibilidades respectivas de Sandell foram de 0,0233 e 0,0123 μg cm-2. Os LOD e os LOQ para o metodo A calculados foram 0,37 e 1,13 μg mL-1e os valores correspondentes para o metodo B foram 0,16 e 0,48 μg mL-1. A precisao intermediaria, expressa como RSD, encontrou-se na faixa de 0,51 a 2,66%, e a exatidao, expressa como o erro relativo, variou de 0,79 a 2,24%. Os metodos propostos foram aplicados com sucesso ao ensaio de OLP em comprimidos comerciais, com porcentagens medias de recuperacao de 102± 1,59% (metodo A) e de 101± 1,53% (metodo B). A exatidao e a confiabilidade dos metodos foram confirmadas executando testes de recuperacao atraves de procedimento padrao de adicao.

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.

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

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 Beers 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. Osjetljivo i selektivno spektrofotometrijsko određivanje doksiciklin hiklata u farmaceutskim pripravcima koristeći Folin-Ciocalteuov reagens U radu je opisana spektrofotometrijska metoda određivanja doksiciklina (DOX). DOX u bazičnom mediju reducira volframat i/ili molibdat u Folin-Ciocalteuovom (F-C) reagensu pri čemu nastaje modro obojeni kromogen. Obojeni produkt ima apsorpcijski maksimum pri 770 nm. Sustav podliježe Beerovom zakonu u koncentracijskom području 0,75-12,0 μg mL-1 DOX. Molarni apsorpcijski koeficijent iznosi 2,78 × 104 L mol-1 cm-1. Granice kvantifikacije i detekcije su 0,20, odnosno 0,08 μg mL-1. Unutar linearnog područja procijenjene su ispravnost i preciznost unutar jedne i više eksperimentalnih serija. Ispravnost je iznosila 101,0 ± 1,7 %, relativna pogreška ≤ 2,7 %, a relativna standardna devijacija ≤ 2,5 %. Ispitana je i primjenjivost predložene metode na praškasti uzorak doksiciklina i komercijalne tablete. Usporedbom rezultata dobivenih predloženom metodom i oficijelnom BP metodom nisu ustanovljene značajne razlike. Opisana metoda je jednostavna, brza, ispravna i precizna.

Simple UV and visible spectrophotometric methods for the determination of doxycycline hyclate in pharmaceuticals

Doxycycline hyclate (DOX), a broad spectrum antibiotic with activity against a wide range of gram-positive and gram-negative bacteria, is widely used as a pharmacological agent and as an effector molecule in inducible gene expression system. Three simple, selective, rapid, accurate, precise and cost-effective spectrophotometric methods for the determination of DOX in bulk drug and in tablets have been developed and validated. First method (method A) is based on the measurement of absorbance of DOX in 0.1 M HCl at 240 nm. The second method (method B) is based on the measurement of yellow chromogen at 375 nm which is formed in 0.1 M NaOH. The third method is based on the measurement of 2: 1 complex formed between DOX and iron(III) in H2SO4 medium, the complex peaking at 420 nm (method C). The optimum conditions for all the three methods are optimized. Beer’s law was obeyed over the ranges 2.5–50.0, 1.50–30.0 and 10–100 g/mL for method A, method B and method C, respectively. The apparent molar absorptivity values are calculated to be 1.03 × 104, 1.73 × 104, and 5.21 × 103 L mol−1 cm−1 for method A, method B, and method C, respectively. The Sandell sensitivity, limit of detection (LOD) and limit quantification (LOQ) values are also reported. All the methods were validated in accordance with current ICH guidelines. The developed methods were employed with high degree of precision and accuracy for the estimation of total drug content in commercial tablet formulations of DOX.

Spectrophotometric Determination of Mycophenolate Mofetil as Its Charge-Transfer Complexes with Two π-Acceptors

Two simple, selective, and rapid spectrophotometric methods are described for the determination of mycophenolate mofetil (MPM) in pure form and in tablets. Both methods are based on charge-transfer complexation reaction of MPM with p-chloranilic acid (p-CA) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in dioxane-acetonitrile medium resulting in coloured product measurable at 520 nm (p-CA) or 580 nm (DDQ). Beers law is obeyed over the concentration ranges of 40–400 and 12–120 μg mL−1 MPM for p-CA and DDQ, respectively, with correlation coefficients (r) of 0.9995 and 0.9947. The apparent molar absorptivity values are calculated to be 1.06 × 103 and 3.87 × 103 L mol−1 cm−1, respectively, and the corresponding Sandells sensitivities are 0.4106 and 0.1119 μg cm−1. The limits of detection (LOD) and quantification (LOQ) are also reported for both methods. The described methods were successfully applied to the determination of MPM in tablets. Statistical comparison of the results with those of the reference method showed excellent agreement. No interference was observed from the common excipients present in tablets. Both methods were validated statistically for accuracy and precision. The accuracy and reliability of the methods were further ascertained by recovery studies via standard addition procedure.

Titrimetric assay of ofloxacin in pharmaceuticals using cerium(IV) sulphate as an oxidimetric reagent

Two titrimetric methods which are simple, rapid, cost-effective and eco-riendly are described for the determination of ofloxacin (OFX) in bulk drug and in tablet formulations based on the oxidation of OFX by Ce(IV) sulphate. In direct titrimetry (method A), the acidified solution of OFX is titrated directly with Ce(IV) sulphate using ferroin as indicator, and indirect titrimetry (method B) involves the addition of known excess of Ce(IV) sulphate to an acidified solution of OFX followed by the determination of unreacted oxidant by back titration with ferrous ammonium sulphate (FAS) using the same ferroin indicator. In both the methods, the amount of Ce(IV) sulphate reacted corresponds to OFX concentration. Method A and method B permit the determination of OFX over the concentration range of 1.5–15 mg in both the methods and the quantitation is based on a 1: 5 reaction stoichiometry (OFX: Ce (IV) sulphate). The methods were statistically evaluated by calculating percent relative error (% RE) for accuracy and percent relative standard deviation (% RSD) for precision, and were applied successfully to the determination of OFX in tablets with mean recoveries in the range of 96.50–98.42%. No interference was observed from common additives found in pharmaceutical preparations. The accuracy and reliability of the methods were further ascertained by performing recovery tests s standard-addition technique.

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 × 104 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 Sandells 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.

Spectrophotometric assay of pioglitazone hydrochloride using permanganate in acidic and basic media

Article history: Received December 22, 2017 Received in revised form March 21, 2018 Accepted March 25, 2018 Available online March 25, 2018 Pioglitazone hydrochloride (PGH) is an oral anti-hyperglycemic agent used in the treatment of type-2 diabetes mellitus. Potassium permanganate was found to oxidize PGH both in acidic and basic conditions, based on which two simple and sensitive methods were developed for its determination in bulk sample and tablets, and validated. In the first method (indirect method), PGH was reacted with a measured excess of standard permanganate in H2SO4 medium, and the residual oxidant was determined by measuring its absorbance at 550 nm. The second method (Direct method) entails treating PGH with permanganate in NaOH medium, followed by the measurement of the resulting bluish-green manganite at 610 nm. Experimental variables affecting the reactions were studied and optimized. Under optimum conditions, linear relationships with good correlation coefficients were found between absorbance and concentration in the ranges, 1.25 – 25 μg mL-1 (Indirect method) and 1-12 μg mL-1 (Direct method) with respective molar absorptivity values of 1.10 × 104 and 2.77 × 104 l mol-1 cm-1. The limits of detection (LOD) and quantification (LOQ) were 0.36 and 1.08 (Indirect method) and 0.23 and 0.69 μg mL-1 (Direct method). Intra-day and inter-day precisions were satisfactory, with %RSD values of ≤2.11, and the respective accuracies were excellent with %RE values of ≤2. The methods were also validated for robustness, ruggedness and selectivity. The methods were applied to the determination of PGH in its tablets with good accuracy and precision, and no interference from the tablet additives was encountered. The results were also compared with those obtained by a reference method.

Application of bromate-bromide mixture as a green brominating agent for the spectrophotometric determination of atenolol in pharmaceuticals

Two highly sensitive spectrophotometric methods are proposed for the quantification of atenolol (ATN) in pure drug as well as in pharmaceutical formulations. The methods are based on the bromination reaction of ATN with a known excess of bromate-bromide mixture in acid medium followed by the determination of unreacted bromine. The residual bromine is determined by its reaction with excess iodide and the liberated iodine (I3□) is either measured at 360 nm (method A) or reacted with starch followed by the measurement of the starch-iodine chromogen at 570 nm (method B). Under the optimum conditions, ATN could be assayed in the concentration ranges of 0.5-9.0 and 0.3-6.0μg mL-1 for method A and method B, respectively, with corresponding molar absorptivity values of 2.36×104 and 2.89×104 L/mol.cm. Sandell’s sensitivity values are found to be 0.0113 and 0.0092 μg/cm2 for method A and method B, respectively. The proposed methods were successfully applied to the analysis of different commercial brands of pharmaceutical formulations and the results obtained by the proposed methods were in good agreement with those obtained using the reference method. The reliability of the methods was further ascertained by recovery studies using standard- addition method.