Rasha A. Shaalan

Spectrophotometric and spectrofluorometric methods for the assay of lisinopril in single and multicomponent pharmaceutical dosage forms

Simple and sensitive methods are described for the assay of lisinopril in tablets. The first method (A) is based on the reaction of the drug with chloranil in aqueous solution of pH 9.5 to give yellow colour measured at 346 nm. The second method (B) is based upon the interaction of lisinopril with dichlone resulting in the formation of an intense purple colour measured at 580 nm. The third method (C) depends on the reaction of the drug with acetylacetone and formaldehyde to form a coloured condensation product measured at 356 nm and also has a strong fluorescence at 475 nm (lambda(ex) 410 nm). This method is extended to determine lisinopril in binary mixtures with hydrochlorothiazide. The last method (D) depends on measuring the first and second derivative spectra of lisinopril. Moreover, the derivative method is used as stability-indicating method where lisinopril can be determined in presence of its degradation products. The proposed methods proved to be suitable for a rapid quality control of commercial dosage forms. The results obtained were precise and accurate.

Simultaneous spectrofluorimetric determination of amlodipine besylate and valsartan in their combined tablets

Amlodipine, a dihydropyridine calcium channel blocker, and valsartan, an angiotensin II receptor blocker, are co-formulated in a single-dose combination for the treatment of hypertension. The combination is used by patients whose blood pressure is not adequately controlled on either component monotherapy. This work describes a simple, sensitive, and reliable spectrofluorimetric method for the simultaneous determination of the two antihypertensive drugs; amlodipine besylate (AML) and valsartan (VAL) in their combined tablets. The method involved measurement of the native fluorescence at 455 nm (λ(Ex) 360 nm) and 378 nm (λ(Ex) 245 nm) for AML and VAL, respectively. Analytical performance of the proposed spectrofluorimetric procedure was statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness, detection, and quantification limits. Regression analysis showed good correlation between fluorescence intensity and concentration over the concentration ranges 0.2-3.6 and 0.008-0.080 µg mL⁻¹ for AML and VAL, respectively. The limits of detection were 0.025 and 0.0012 µg mL⁻¹ for AML and VAL, respectively. The proposed method was successfully applied for the assay of the two drugs in their combined pharmaceutical tablets with recoveries not less than 98.85%. No interference was observed from common pharmaceutical additives. The results were favourably compared with those obtained by a reference spectrophotometric method.

Spectrophotometric methods for the determination of benazepril hydrochloride in its single and multi-component dosage forms

Three sensitive and accurate methods are presented for the determination of benazepril in its dosage forms. The first method uses derivative spectrophotometry to resolve the interference due to formulation matrix. The second method depends on the color formed by the reaction of the drug with bromocresol green (BCG). The third one utilizes the reaction of benazepril, after alkaline hydrolysis, with 3-methylbenzothialozone (MBTH) hydrazone where the produced color is measured at 593 nm. The latter method was extended to develop a stability-indicating method for this drug. Moreover, the derivative method was applied for the determination of benazepril in its combination with hydrochlorothiazide. The proposed methods were applied for the analysis of benazepril in the pure form and in tablets. The coefficient of variation was less than 2%.

Spectrophotometric Determination of Enalapril Maleate and Ramipril in Dosage Forms

Abstract Three sensitive and accurate spectrophotometric methods have been developed for the assay of enalapril maleate and ramipril, each in its dosage forms. These methods depend on the reaction of the drugs with p-chloranilic acid, the reaction with picric acid, and the ion-pair salt formation with bromocresol green. The proposed methods have been applied to the analysis of these drugs in their commercial tablets. The results obtained were precise and accurate.

Spectrophotometric and Spectrofluorimetric Methods for the Determination of Terazosin in Dosage Forms

Abstract Five simple and accurate methods are presented for the determination of terazosin (TZ) in tablets. These methods are based on: the direct measurements of the first and second derivative spectra of samples (A), the reaction of TZ with chloranil (CH) in aqueous solution of pH 9 to give an intense yellow color measured at 340 nm (B), the reaction of the drug with mercurochrome (MER) in aqueous alkaline medium to give an intense red color measured at 543 nm (C), the formation of an ion-pair salt between the drug and bromocresol purple (BCP) with subsequent absorbance measurements at 412 nm (D), and a sensitive fluorimetric method (E). The latter method was extended to determine TZ in presence of its degradation products.

Validated Stability-Indicating HPLC-DAD Method for the Simultaneous Determination of Diclofenac Sodium and Diflunisal in Their Combined Dosage Form

A simple, rapid, and highly selective HPLC-DAD method was developed for the simultaneous determination of diclofenac sodium (DIC) and diflunisal (DIF) in pure form and in their combined formulation. Effective chromatographic separation was achieved using a Zorbax SB-C8 (4.6×250 mm, 5 μm particle size) column with a mobile phase composed of 0.05 M phosphoric acid, acetonitrile, and methanol in the ratio of 40:48:12 (by volume). The mobile phase was pumped isocratically at a flow rate of 1 mL/min, and quantification of the analytes was based on measuring their peak areas at 228 nm. The retention times for diflunisal and diclofenac were about 7.9 and 9.5 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to system suitability, linearity, ranges, precision, accuracy, specificity, robustness, detection, and quantification limits. Calibration curves were linear in the ranges of 5–100 μg/mL for both drugs with correlation coefficients >0.9998. The proposed method proved to be selective and stability-indicating by the resolution of the two analytes from four of their related substances and potential impurities as well as from forced-degradation (hydrolysis, oxidation, photolysis, and dry heat) products. The validated HPLC method was successfully applied to the analysis of DIC and DIF in their combined dosage form (suppositories). The proposed method made use of the diode array detector (DAD) as a tool for peak identity and purity confirmation.

GRADIENT HPLC-DAD DETERMINATION OF THE ANTIHYPERTENSIVE MIXTURE OF AMLODIPINE BESYLATE, VALSARTAN, AND HYDROCHLOROTHIAZIDE IN COMBINED PHARMACEUTICAL TABLETS

A triple drug combination of amlodipine besylate (AML), valsartan (VAL), and hydrochlothiazide (HCT) was recently approved by the European Medicines Agency and the FDA for the treatment of moderate and severe hypertension. In this work, a simple, rapid, and reliable HPLC-DAD method was described for the simultaneous determination of the three antihypertensives. Chromatographic separation was achieved using Zorbax SB-C8 column with gradient elution of the mobile phase composed of 0.025 M phosphoric acid and acetonitrile. The gradient elution started with 30% (by volume) acetonitrile, ramped up linearly to 70% in 3 min then kept constant for the remainder of the run. The flow rate was 1 mL/min. The multiple wavelength detector was set at 238 nm for measurement of AML and 225 nm for VAL and HCT. Quantification was based on measuring peak areas. The analytes were resolved with retention times 4.2, 4.7, and 6.5 min for HCT, AML, and VAL, respectively. Analytical performance of the proposed procedure was validated with respect to system suitability, linearity, ranges, precision, accuracy, robustness, detection, and quantification limits. The linearity ranges were 5–100, 2.5–200, and 2.5–100 µg/mL for AML, VAL, and HCT, respectively. The validated HPLC method was extended to the analysis of this combination in several laboratory-prepared mixtures of different ratios. Specificity was tested by resolution of the three analytes from several pharmaceutical compounds of various medicinal categories. Finally, Exforge HCT® tablets were assayed using the developed procedure where no interfering peaks were encountered from the tablet additives.

Spectrophotometric Determination of Ternary Mixtures by the Derivative Ratio Spectrum-Zero Crossing Method

Abstract A new spectrophotometric method is introduced for the assay of ternary mixtures with overlapping spectra. The method is based on the use of the first derivative of the ratio spectra and measurements of zero-crossing wavelengths. The ratio spectra were obtained by dividing the absorption spectrum of the mixture by that of one of the components. The concentration of the other components are then determined from their respective calibration graphs treated similarly. The method has been applied for the resolution of two ternary mixtures, namely, dipyridamole, aspirin and salicylic acid (I) and dipyridamole, oxazepam and 2-amino-5-chlorobenzophenone (II). Salicylic acid and benzo-phenone derivative are the degradation products of aspirin and oxazepam, respectively. The proposed method was applied for the assay of these combinations in synthetic mixtures and in commercial dosage forms. The results obtained were precise and accurate.

Improved spectrofluorimetric methods for determination of penicillamine in capsules

AbstractTwo simple, sensitive and specific fluorimetric methods have been developed for the determination of Penicillamine (PNC), a sulphur containing compound. Method (I) involves the reaction of PNC with 2′,7′-bis(acetoxymercuri)-fluorescein (AMF) in the presence of Kolthoff’s buffer, pH 8.2, with subsequent measurement of fluorescence spectra at 520 nm (λEx 497 nm). Method (II) is based on PNC being oxidized into penicillaminic acid using Cerium (IV) in an acidic medium. Method sensitivity has been improved using sodium triphosphate which enhances the luminescence intensity of Ce(III). Fluorescence spectra were then measured at 348 nm (λEx 293 nm). The reaction conditions and the fluorescence spectral properties have been investigated for both methods. Under the described conditions, the proposed methods were applicable over the concentration ranges 0.0048 − 0.0288 µg mL−1 and 0.096 − 0.288 µg mL−1 with mean percentage recoveries 99.95 ± 1.29 and 100.04 ± 1.10 for methods I and II, respectively. The proposed methods were validated in terms of accuracy, precision, LOD and LOQ and robustness and then were successfully applied to the determination of PNC in bulk powder and in capsules as well as in the presence of the related disulphide. The results obtained were determined to be in good agreement with those obtained using a previously reported method.