Samah S. Abbas

Spectrophotometric and spectrodensitometric determination of Clopidogrel Bisulfate with kinetic study of its alkaline degradation

Four sensitive, selective and precise stability-indicating methods for the determination of Clopidogrel Bisulfate (CLP) in presence of its alkaline degradate and in pharmaceutical formulations were developed and validated. Method A is a second derivative (D(2)) spectrophotometric one, which allows the determination of CLP in presence of its alkaline degradate at 219.6, 270.6, 274.2 and 278.4 nm (corresponding to zero-crossing of the degradate) over a concentration range of 4-37 microg mL(-1) with mean percentage recoveries 99.81+/-0.893, 99.72+/-0.668, 99.88+/-0.526 and 100.46+/-0.646, respectively. CLP can be determined in the presence of up to 65% of its degradate. D(2) method was used to study the kinetic of CLP alkaline degradation that was found to follow a first-order reaction. The t(1/2) was 6.42 h while K (reaction rate constant) was 0.1080 mol/h. Method B is the first derivative of the ratio spectra (DD(1)) spectrophotometric method, by measuring the peak amplitude at 217.6 and 229.4 nm using acetonitrile and CLP can be determined in the presence of up to 70% of its degradate. The linearity range was 5-38 microg mL(-1) with mean percentage recoveries 99.88+/-0.909 and 99.70+/-0.952, respectively. Method C based on the determination of CLP by the bivariate calibration depending on simple mathematic algorithm which provides simplicity and rapidity. The method depends on quantitative evaluation of the absorbance at 210 and 225 nm over a concentration range 5-38 microg mL(-1) with mean percentage recovery 99.27+/-1.115. CLP can be determined in the presence of up to 70% of its degradate. Method D is a TLC-densitometric one, where CLP was separated from its degradate on silica gel plates using hexane:methanol:ethyl acetate (8.7:1:0.3, v/v/v) as a developing system. This method depends on quantitative densitometric evaluation of thin layer chromatogram of CLP at 248 nm over a concentration range of 0.6-3 microg/band with mean percentage recovery 99.97+/-1.161. CLP can be determined in the presence of up to 90% of its alkaline degradate. The selectivity of the proposed methods was checked using laboratory prepared mixtures. The proposed methods have been successfully applied to the analysis of CLP in pharmaceutical dosage forms without interference from other dosage form additives and the results were statistically compared with the official method.

Stability indicating method for determination of nortriptyline hydrochloride using 3-methyl-2-benzothiazolinone hydrazone (MBTH).

A spectrophotometric procedure is described for determination of nortriptyline hydrochloride in pure and dosage form as well as in the presence of its degradate. 3-Methyl-2-benzothiazolinone hydrazone (MBTH) has been used as the chromogenic reagent, where aqueous solutions of the drug and reagent are treated with cerium(IV) ammonium sulphate in an acidic medium. Nortriptyline hydrochloride reacts to give a blue coloured product having two absorption maxima at 619 and 655 nm. Various parameters affecting the reaction have been studied. Beers law is obeyed in the concentration range of 24-216 microg ml(-1) of nortriptyline hydrochloride, with mean percentage recoveries of 100.22+/-0.870 and 100.66+/-0.642% for both maxima, 619 and 655 nm, respectively. Results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (1993) method.

Validated Chromatographic Methods for Determination of Perindopril and Amlodipine in Pharmaceutical Formulation in the Presence of their Degradation Products

Two specific, sensitive, and precise stability-indicating chromatographic methods have been developed, optimized and validated for determination of perindopril arginin (PER) and amlodipine besylate (AML) in their mixtures and in the presence of their degradation products. The first method was based on thin-layer chromatography (TLC) combined with densitometric determination of the separated bands. Adequate separation was achieved using silica gel 60 F254 TLC plates and ethyl acetate-methanol-toluene-ammonia solution, 33% (6.5:2:1:0.5 by volume), as a developing system. The second method was based on high-performance liquid chromatography, by which the proposed components were separated on a reversed-phase C18 analytical column using a mobile phase consisting of phosphate buffer (pH 2.5, 0.01 M)-acetonitrile-tetrahydrofuran (60:40:0.1% by volume) with ultraviolet detection at 218 nm. Different parameters affecting the suggested methods were optimized for maximum separation of the cited components. System suitability parameters of the two developed methods were also tested. The suggested methods were validated in compliance with the ICH guidelines and were successfully applied for the quantification of PER and AML in their commercial tablets. Both methods were also statistically compared to each other and to the reference methods with no significant differences in performance.

SPECTROPHOTOMETRIC AND STABILITY INDICATING HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF NORTRIPTYLINE HYDROCHLORIDE AND FLUPHENAZINE HYDROCHLORIDE

ABSTRACT Spectrophotometric and high performance liquid chromatographic procedures are described for determination of nortriptyline hydrochloride and fluphenazine hydrochloride. The first procedure is based on application of first derivative of ratio spectra (1DD) for quantitative determination of nortriptyline hydrochloride in presence of fluphenazine hydrochloride. Secondly, an accurate, sensitive and stability indicating method has been introduced for determination of nortriptyline hydrochloride and fluphenazine hydrochloride in both bulk powder and in dosage form. In the derivative ratio method, Beers law is obeyed in the concentration ranges of 8–32 µg mL−1 and 4–32 µg mL−1 of nortriptyline hydrochloride at wavelengths 271.4 and 284.2 nm, respectively. In high performance liquid chromatographic method, linear relationship in the range of 0.6–3.6 µg mL−1 and 1.2–4.2 µg mL−1 for nortriptyline hydrochloride and fluphenazine hydrochloride, respectively, was obtained. The mobile phase used was 0.05 M ammonium acetate : methanol : acetonitrile (4 : 1 : 5 v/v/v), and detection was done spectrophotometrically at 254 nm. Results were statistically analyzed and compared with those obtained by applying the British Pharmacopoeia (2000) method.

Validated stability indicating methods for determination of nitazoxanide in presence of its degradation products

Three sensitive, selective and reproducible stability-indicating methods are presented for determination of nitazoxanide (NTZ), a new anti-protozoal drug, in presence of its degradation products. Method A utilizes the first derivative of ratio spectra spectrophotometry by measurement of the amplitude at 364.4 nm using one of the degradation products as a divisor. Method B is a chemometric-assisted spectrophotometry, where principal component regression (PCR) and partial least squares (PLS) were applied. These two approaches were successfully applied to quantify NTZ in presence of degradation products using the information included in the absorption spectra in the range 260–360 nm. Method C is based on the separation of NTZ from its degradation products followed by densitometric measurement of the bands at 254 nm. The separation was carried out on silica gel 60F254, using chloroform–methanol–ammonia solution–glacial acetic acid (95:5:1:1 by volume, pH=5.80) as a developing system. These methods are suitable as stability-indicating methods for the determination of NTZ in presence of its degradation products either in bulk powder or in pharmaceutical formulations. Statistical analysis of the results has been carried out revealing high accuracy and good precision.

Spectrophotometric and spectrodensitometric determination of triamterene and xipamide in pure form and in pharmaceutical formulation.

Sensitive and validated UV-spectrophotometric, chemometric and TLC-densitometric methods were developed for determination of triamterene (TRM) and xipamide (XIP) in their binary mixture, formulated for use as a diuretic, without previous separation. Method A is the isoabsorptive point spectrophotometry, in which TRM concentration alone can be determined at its λ(max) while XIP concentration can be determined by measuring total concentration of TRM and XIP at their isoabsorptive point followed by subtraction. Method B is the ratio subtraction spectrophotometry, where XIP can be determined by dividing the spectrum of the mixture by the spectrum of TRM (as a divisor) followed by subtracting the constant absorbance value of the plateau region, then finally multiplying the produced spectrum by the spectrum of the divisor, while TRM concentration can be determined at its λ(max). Method C is a chemometric-assisted spectrophotometry where classical least squares, principal component regression, and partial least squares were applied. Method D is a TLC-densitometry; this method depends on quantitative densitometric separation of thin layer chromatogram of TRM and XIP using silica gel plates at 254 nm. The proposed methods were successfully applied for the analysis of TRM and XIP in their pharmaceutical formulation and the results were statistically compared with the established HPLC method.

Spectrophotometric determination of isopropamide Iodide and trifluoperazine hydrochloride in presence of trifluoperazine oxidative degradate

Four sensitive, selective and precise stability indicating methods for the determination of isopropamide iodide (ISO) and trifluoperazine hydrochloride (TPZ) in their binary mixture and in presence of trifluoperazine oxidative degradate (OXD). Method A is a derivative spectrophotometric one, where ISO was determined by first derivative (D(1)) at 226.4 nm while TPZ was determined by second derivative (D(2)) at 270.2 nm. Method B is the first derivative of the ratio spectra (DD(1)) spectrophotometric method, ISO can be determined by measuring the peak amplitude at 227.4 nm using 5 microg mL(-1) of OXD as a divisor, while TPZ can be determined by measuring the peak amplitude at 249.2 and 261.4 nm using 15 microg mL(-1) of ISO as a divisor. Method C is the isoabsorptive spectrophotometric method. This method allows determination of ISO and TPZ in their binary mixture by measuring total concentration of ISO and TPZ at their isoabsorptive point at lambda(229.8) nm (Aiso1) while TPZ concentration alone can be determined at lambda(max) 311.2 nm, then ISO concentration can be determined by subtraction. On the same basis TPZ can be determined in presence of ISO and OXD, where OXD concentration alone was determined by measuring the peak amplitude at lambda(281.6) and lambda(309.4) nm while total concentration of TPZ and OXD was determined at their isoabsorptive points at (Aiso2 = 270.2 nm), (Aiso3 = 310.6 nm) and (Aiso4 = 331.8 nm) then TPZ concentration was determined by subtraction. Method D is the multivariate calibration techniques [the classical least squares (CLS), principal component regression (PCR) and partial least squares (PLS)], using the information contained in the absorption spectra of ISO, TPZ and OXD mixtures. The selectivity of the proposed methods was checked using laboratory prepared mixtures. The proposed methods have been successfully applied to the analysis of ISO and TPZ in pharmaceutical dosage form without interference from other dosage form additives and the results were statistically compared with the reported method.

Spectrophotometric Determination of Triamterene Using Some Acid Dyes

Abstract Two acid dye reagents have been utilized for spectrophotometric determination of triamterene in pure form and in pharmaceutical preparations. The dyes used are bromophenol blue (B. P. B), and bromothymol blue (B. T. S. They form a chloroform-soluble, coloured ion association complex with triamterene, at pH 3.4 and 3.2 using B. P. B and B. T. B, respectively. The formed complex could be extracted and measured spectrophotometrically at 417 nm for both dyes. The molar ratio of the formed drug-dye ion association complex is found to be 1:1 for both dyes used, as deduced by applying Jobs method. Linearity was obtained using concentration ranges of 2.5–10 μg, and 2.5–15 μg. ml−1 of triamterene with B. P. B. and B. T. B. respectively. The validity of the procedure was assessed by applying the standard addition technique. Results obtained by using the proposed procedure were statistically analysed and compared with those obtained by adopting the pharmacopoeial method.

Thiopental and Phenytoin as Novel Ionophores for Potentiometric Determination of Lead (II) Ions

Two novel polymeric membrane sensors for the analysis of Pb(II) have been developed based on two therapeutic drugs, thiopental (TP) and phenytoin (PT) as two new ionophores and potassium tetrakis(p-chlorophenyl) borate (KTpClPB) as a lipophilic additive, in plasticized PVC membranes. The sensors show a Nernstian response for Pb(II) ions over the wide concentration ranges of 1×10−2 – 7×10−6 M and 1×10−2 – 8×10−6 M for the sensors based on thiopental and phenytoin, respectively. The proposed sensors have a fast response time and can be used for more than nine weeks without any considerable divergence in potentials. The sensors exhibit comparatively good selectivity with respect to alkaline, alkaline earth and some transition and heavy metal ions. They were employed for direct determination of lead in solder alloys and in galena rocks with a good agreement with the obtained results by atomic absorption spectroscopy.

Utility of p-chloranilic Acid and 2,3 Dichloro-5,6-dicyano p-Benzoquinone (DDQ) for the Spectrophotometric Determination of Triamterene

Abstract Two simple and sensitive spectrophotometric procedures are suggested for analysis of triamterene. The first procedure is based on the reaction of triamterene with p-chloranilic acid (p-CA) in methylene chloride to form a highly stable coloured product, exhibiting maximum absorbance at λ 530 nm. Beers law is obeyed in the range of 40–220 μg.ml−1 with a mean percentage accuracy of 99.98 ± 0.446. Limit of determination is 20 μg.ml−1. In the second procedure, the drug is determined via charge transfer complex formation with 2,3 dichloro-5,6-dicyano p-benzoquinone (DDQ) using methylene chloride as a solvent. Here the reaction product has two well defined maxima at 460 nm and 530 nm where each has been utilized for quantitative determination. Beers law is obeyed in concentration ranges of 25–125 μg.ml−1 and 25–150 μg.ml−1 with mean percentage accuracies of 99.92 ± 0.449 and 100.00 ± 0.511 for both maxima. 460 and 530 nm. respectively. Limit of determination is 12.5 μg.ml−1 at both maxima. Optimum con...