Extractive Spectrophotometric Determination of Quetiapine Fumarate in Pharmaceuticals and Spiked Human Urine

A simple, sensitive and selective extractive spectrophotometric method for the determination of quetiapine fumarate (QTF) in bulk drug, tablets and spiked human urine sample is described. The method is based on the formation of a chloroform extractable yellow ion-pair complex between basic nitrogen of the drug (QTF) and the dye quinoline yellow (QY) in acetate-hydrochloride buffer (pH 2.56) medium. The formed ion-pair complex exhibited an absorption maximum at 420 nm. Beer’s law is obeyed over the concentration range 2.5–25 µg mL–1 with an apparent molar absorptivity value of 2.02 × 104 L mol–1 cm–1. The Sandell sensitivity, limits of detection (LOD) and quantification values are also reported. The composition of the ion-pair was established by Job’s continuous variations method and it was found to be 1:1 (QTF:QY). The proposed method was successfully applied for the determination of QTF in bulk drug, tablets and spiked human urine without any interference. (doi: 10.5562/cca1770

Spectrophotometric Determination of Isoxsuprine Hydrochloride as Base Form in Pharmaceutical Formulation through Charge Transfer Complexation

Two simple and selective spectrophotometric methods are described for the determination of isoxsuprine hydrochloride (ISX·HCl) as base form in bulk drug and in injections and tablets. The methods are based on the molecular charge-transfer complexation of ISX base (ISX) with either p-chloranilic acid (PCA) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The intense colored radical anions formed on dissociation, are quantitated at 520 nm (PCA method) or 600 nm (DDQ method). The optimum assay conditions were optimized. Beer\u27s law is obeyed in the concentration ranges 5.28 × 10–5 to 42.2 × 10–5 mol dm–3 in PCA method and 0.79 × 10–5 to 10.6 × 10–5 mol dm–3 in DDQ method, with respective molar absorptivity values of 1.32 × 103 and 6.55 × 103 dm3 mol–1 cm–1. The reaction stoichiometry in both methods was evaluated by either Job’s method or limiting logarithmic method and was found to be 1:1 (ISX: PCA, ISX: DDQ). Developed methods were validated according to ICH guidelines and found to be accurate and precise

Optimized and validated spectrophotometric methods for the determination of hydroxyzine hydrochloride in pharmaceuticals and urine using iodine and picric acid

Two simple, rapid, cost-effective and sensitive spectrophotometric procedures are proposed for the determination of hydroxyzine dihydrochloride (HDH) in pharmaceuticals and in spiked human urine. The methods are based on the charge transfer complexation reaction of the drug with either iodine (I2) as a σ-acceptor (method A) in dichloromethane or picric acid (PA) as a π-acceptor (method B) in chloroform. The coloured products exhibit absorption maxima at 380 and 400 nm for I2 and PA, respectively. The Beer Law was obeyed over the concentration ranges of 1.25-15 and 3.75-45 μg mL-1 for method A and method B, respectively. The molar absorptivity values, Sandell sensitivities, limits of detection (LOD) and quantification (LOQ) are reported. The accuracy and precision of the methods were evaluated on intra-day and inter-day basis. The proposed methods were successfully applied for the determination of HDH in tablets and spiked human urine

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 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

Determination of olanzapine by spectrophotometry using permanganate

Two new spectrophotometric methods using permanganate as the oxidimetric reagent for the determination of olanzapine (OLP) were developed and validated as per the current ICH guidelines. The methods involved the addition of known excess of permanganate to OLP in either acid or alkaline medium followed by the determination of unreacted permanganate at 550 nm (method A) or bluish-green color of manganate at 610 nm (method B). The decrease in absorbance in method A or increase in absorbance in method B as a function of concentration of OLP was measured and related to OLP concentration. Under optimized conditions, Beer's law was obeyed over the ranges 2.0 to 20 and 1.0 to 10 μg mL-1 in method A and method B, respectively. The calculated molar absorptivity values were 1.34 x 10(4) and 2.54 x 10(4) l mol-1cm-1 for method A and method B respectively, and the respective Sandell sensitivities were 0.0233 and 0.0123 μg cm-2. The LOD and LOQ for method A were calculated to be 0.37 and 1.13 μg mL-1and the corresponding values for method B were 0.16 and 0.48 μg mL-1. Intermediate precision, expressed as RSD was in the range 0.51 to 2.66 %, and accuracy, expressed as relative error ranged from 0.79 to 2.24 %. The proposed methods were successfully applied to the assay of OLP in commercial tablets with mean percentage recoveries of 102 ±1.59 % (method A) and 101 ±1.53 % (method B). The accuracy and reliability of the methods were further confirmed by performing recovery tests via standard addition procedure.Dois métodos espectrofotométricos novos, usando o permanganato como o reagente oxidimétrico para a determinação da olanzapina (OLP) foram utilizados e validados de acordo com as diretrizes atuais do ICH. Os métodos envolveram a adição de excesso conhecido de permanganato à OLP em meio ácido ou alcalino, determinando-se o permanganato que não reagiu em 550 nm (método A), ou pela cor verde-azulada do manganato a 610 nm (método B). A diminuição da absorbância no método A ou o aumento da absorbância no método B, em função da concentração de OLP, foi medida e relacionada à concentração de OLP. Sob condições otimizadas, a lei de Beer foi obedecida, nas faixas de concentração de 2,0 a 20 e 1,0 a 10 ao μg mL-1, no método A e no método B, respectivamente. Os valores de absortividade molar foram de 1,34 x 104 e 2,54 x 104 l mol-1cm-1 para o método A e para o método 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 método A calculados foram 0,37 e 1,13 μg mL-1e os valores correspondentes para o método B foram 0,16 e 0,48 μg mL-1. A precisão intermediária, expressa como RSD, encontrou-se na faixa de 0,51 a 2,66%, e a exatidão, expressa como o erro relativo, variou de 0,79 a 2,24%. Os métodos propostos foram aplicados com sucesso ao ensaio de OLP em comprimidos comerciais, com porcentagens médias de recuperação de 102± 1,59% (método A) e de 101± 1,53% (método B). A exatidão e a confiabilidade dos métodos foram confirmadas executando testes de recuperação através de procedimento padrão de adição

Synthesis and characterization of tetralones as intermediates for podophyllotoxin analogues

Podophyllotoxin has captured the attention of chemists all over the world for its biological activity. It was isolated from many plants of Podophyllum species such as Podophyllum emodi, Podophyllum peltatum and others. It mainly exhibits anticancer, antimitotic, antimalarial, anti-aids and other activities. Its use is restricted due to its toxicity and unfavourable solubility. It was aimed to synthesize some new heterocyclic analogues of podophyllotoxin by changing the substituents by changing lactone ring with pyrazoline ring and substituents in ring C with hydrogen and methoxy group. Chalcones were prepared by Claisen-Schmidt reaction of 1,3-methylene dioxyacetophenone with benzaldehyde and p-anisaldehyde. The reaction of chalcone with trimethylsulphoxonium iodide in presence of sodium hydride gave cyclopropyl ketone. Intramolecular cyclization reaction of cyclopropyl ketone gave tetralone intermediates of podophyllotoxin. They are obtained in good yields. The structure of all the products was confirmed by spectral data

Sensitive and Selective Extractive Spectrophotometric Method for the Determination of Hydroxyzine Dihydrochloride in Pharmaceuticals 233 Sensitive and Selective Extractive Spectrophotometric Method for the Determination of Hydroxyzine Dihydrochloride in P

Abstract. Hydroxyzine dihydrochloride (HDH), a piperazine H 1 -receptor antagonist and antihistamine, is a rapid acting anxiolytic used principally as an anti-emetic. A sensitive, selective, and precise and accurate spectrophotometric method based on the formation of an ion-pair with orange II (ORG II) as ion-pair complexing agent was developed and validated for the determination of HDH in pharmaceuticals. The chloroform-extractable ion-pair complex exhibited an absorption maximum at 480 nm. Optimization of different experimental conditions is described. Beer's law is obeyed in the range of 1.5-15 µg mL -1 with an apparent molar absorptivity value of 2.07 × 10 4 L mol -1 cm -1 and Sandell's sensitivity value of 0.0216 µg cm -2 . The limit of detection (LOD) and limit of quantification (LOQ) are 0.14 and 0.41 µg mL -1 , respectively. A Job's plot of absorbance versus molar ratio of HDH to ORG II indicated (1:2) stoichiometric ratio. Within-and between-day relative standard deviations at three different concentration levels were < 3%. The developed method was successfully applied to commercial tablets. The results obtained were in good agreement with those obtained using the official method. No interference was encountered from co-formulated substances. Recoveries were 96-109 %. Keywords: Spectrophotometry, hydroxyzine, orange II, pharmaceuticals. Resumen. El dihidrocloruro de hidroxicina (HDH), una piperazina antagonista del receptor H 1 y un antihistamínico, es un ansiolítico de acción rápida usado principalmente como anti-emético. Se desarrolló y validó un método espectrofotométrico sensible, selectivo, preciso y exacto basado en la formación de un par iónico con naranja II (ORG II) como un agente complejante para la determinación de HDH en productos farmacéuticos. El par iónico extraído en cloroformo exhibió un máximo de absorción a 480 nm. Se describió la optimización de las diferentes condiciones experimentales. La ley de Beer se obedeció en el intervalo de 1.5-15 µg mL -1 con un valor de absortividad molar aparente de 2.07 × 10 4 L mol -1 cm -1 y un valor de sensibilidad de Sandell de 0.0216 µg cm -2 . El límite de detección (LD) y el límite de cuantificación (LC) son 0.14 y 0.41 µg mL -1 , respectivamente. Una gráfica de Job de absorbancia versus relación molar de HDH y ORG II indicó una relación estequiométrica (1:2). Las desviaciones estándar relativas dentro y entre días, a tres diferentes niveles de concentración, fueron < 3%. El método desarrollado fue aplicado exitosamente a tabletas comerciales. Los resultados obtenidos estuvieron en buena concordancia con los obtenidos con el método oficial. No se encontró ninguna interferencia de parte de las sustancias de la formulación. Las recuperaciones fueron de 96-109 %

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

Brze titrimetrijske i spektrofometrijske metode za određivanje salbutamol sulfata koristeći N-bromsukcinimid

One titrimetric and two spectrophotometric methods which are simple, sensitive and rapid are described for the assay of salbutamol sulphate (SBS) in bulk drug and in tablet dosage forms using N-bromosuccinimide (NBS) and two dyes, rhodamine-B and methylene blue, as reagents. In titrimetry, aqueous solution of salbutamol sulphate is treated with a measured excess of NBS in acetic acid medium and after the oxidation of SBS is complete, the unreacted oxidant is determined iodometrically. Spectrophotometric methods entail addition of a known excess of NBS in acid medium followed by the determination of residual oxidant by reacting with a fixed amount of either rhodamine B and measuring the absorbance at 555 nm (method A) or methylene blue and measuring the absorbance at 665 nm (method B). In all methods, the amount of NBS reacting corresponds to the amount of SBS content. Titrimetric method is applicable over 1.74 × 10-4 – 8.68 × 10-4 mol L-1 range and the reaction stoichiometry is found to be 1:6 (SBS:NBS). In spectrophotometric methods, the absorbance is found to increase linearly with the concentration of SBS, which is corroborated by the correlation of coefficients of 0.9993 and 0.9988 for method A and method B, respectively. The systems obey Beer’s law for 0.251.75 g mL-1 (method A) and 0.55.0 g mL-1 (method B). The calculated apparent molar absorptivity values were found to be 2.10 × 105 and 6.16 × 104 L mol-1 cm-1, for method A and method B, respectively. The limits of detection and quantification are also reported for both spectrophotometric methods. Intra-day and inter-day precision and accuracy for the developed methods were evaluated. The methods were successfully applied to the assay of SBS in tablet and capsule formulations and the results were statistically compared with those of a reference method. No interference was observed from common tablet adjuvants. The accuracy and reliability of the methods were further ascertained by recovery experiments via the standard-addition technique.U radu su opisane jedna titrimetrijska i dvije spektrofotometrijske metode za određivanje salbutamol sulfata (SBS) čiste tvari i u tabletama. Opisane metode su jednostavne, osjetljive i brze, a kao reagense koriste N-bromsukcinimid (NBS) i dva bojila, rodamin-B i metilensko modrilo. U titrimetrijskoj metodi, vodenoj otopini salbutamol sulfata dodana je otopina NBS-a u octenoj kiselini u suvišku, te je nakon potpune oksidacije SBS-a jodometrijski određena količina neizreagiranog oksidansa. U spektrofotometrijskim metodama dodaje se poznati suvišak NBS-a u kiselom mediju nakon čega se neizreagirani suvišak oksidansa određuje nakon reakcije s rodaminom-B mjereći apsorbanciju na 555 nm (metoda A) ili metilenskim modrilom mjereći apsorbanciju na 665 nm (metoda B). U svim metodama, količina NBS-a koji reagira ekvivalentna je sadržaju SBS-a. Titrimetrijska metoda je primjenjiva u rasponu koncentracija od 1,74 × 10-4 do 8,68 × 10-4 mol L-1. SBS i NBS reagiraju u stehiometrijskom omjeru 1:6. U spektrofotometrijskim metodama apsorbancija linearno raste s koncentracijom SBS-a, što je potvrđeno koeficijentima korelacije od 0,9993 za metodu A te 0,9988 za metodu B. Sustavi slijede Beer-ov zakon unutar koncentracija 0,251,75 g mL-1 (metoda A) i 0,55,0 g mL-1 (metoda B). Izračunate vrijednosti molarnog apsorpcijskog koeficijenta iznose 2,10 × 105 za metodu A i 6,16 × 104 L mol-1 cm-1 za metodu B. Granice detekcije i kvantifikacije, ispravnost i preciznost (ponovljivost i intermedijarska preciznost) procijenjene su za obje spektrofotometrijske metode. Metode su uspješno primijenjene za analizu SBS-a u tabletama i kapsulama, a rezultati su statistički uspoređeni s referentnom metodom. Uobičajene pomoćne tvari u tabletama nisu interferirale tijekom određivanja. Ispravnost metoda potvrđena je i metodom standardne adicije