M. I. Walash

Simultaneous Determination of Sitagliptin and Metformin in Pharmaceutical Preparations by Capillary Zone Electrophoresis and its Application to Human Plasma Analysis

A novel, quick, reliable and simple capillary zone electrophoresis CZE method was developed and validated for the simultaneous determination of sitagliptin (SG) and metformin (MF) in pharmaceutical preparations. Separation was carried out in fused silica capillary (50.0 cm total length and 43.0 cm effective length, 49 μm i.d.) by applying a potential of 15 KV (positive polarity) and a running buffer containing 60 mM phosphate buffer at pH 4.0 with UV detection at 203 nm. The samples were injected hydrodynamically for 3 s at 0.5 psi and the temperature of the capillary cartridge was kept at 25 °C. Phenformin was used as internal standard (IS). The method was suitably validated with respect to specificity, linearity, limit of detection and quantitation, accuracy, precision, and robustness. The method showed good linearity in the ranges of 10–100 μg/mL and 50–500 μg/mL with limits of detection of 0.49, 2.11 μg/mL and limits of quantification of 1.48, 6.39 μg/mL for SG and MF, respectively. The proposed method was successfully applied for the analysis of the studied drugs in their synthetic mixtures and co-formulated tablets without interfering peaks due to the excipients present in the pharmaceutical tablets. The method was further extended to the in-vitro determination of the two drugs in spiked human plasma. The estimated amounts of SG/MF were almost identical with the certified values, and their percentage relative standard deviation values (% R.S.D.) were found to be ≤1.50% (n = 3). The results were compared to a reference method reported in the literature and no significant difference was found statistically.

Simultaneous determination of aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide in their triple mixture dosage form by capillary zone electrophoresis

A novel, specific, reliable, and accurate capillary zone electrophoretic method was developed and validated for the simultaneous determination of aliskiren hemifumarate, amlodipine besylate, and hydrochlorothiazide in their triple mixture dosage form. Separation was carried out in a fused-silica capillary (57.0 cm total length and 50.0 cm effective length, 75.6 μm internal diameter) by applying a potential of 17 kV and a running buffer consisting of 40 mM phosphate buffer at pH 6.0 with UV detection at 245 nm. The method was suitably validated with respect to specificity, linearity, LOD, and LOQ, accuracy, precision, and robustness. The method showed good linearity in the ranges 1-10, 2.5-25, and 30-300 μg/mL with LODs of 0.11, 0.33, and 5.83 μg/mL for amlodipine besylate, hydrochlorothiazide, and aliskiren hemifumarate, respectively. The proposed method was successfully applied for the analysis of the studied drugs in their coformulated tablets. The results of the proposed method were statistically compared with those obtained by the RP-HPLC reference method revealing no significant differences in the performance of the methods regarding accuracy and precision.

Colorimetric determination of two nonsteroidal anti-inflammatory drugs using p-dimethylaminocinnamaldehyde

Abstract A colorimetric method for the quantitative determination of diclofenac sodium and mefenamic acid in pure form and in pharmaceutical preparations was developed. It was based on the inter-action of the secondary aromatic amine with p-dimethyl-aminocinnamaldhyde in acidified absolute methanol medium to form very stable red [λmax at 538 nm in case of diclofenac sodium] or blue [λmax at 665 nm in case of mefenamic acid] products. Beers law was obeyed over the ranges 10–80 μg ml−1 and 1–8 μg ml−1 for diclofenac sodium and mefenamic acid, respectively. The reactants were heated on a boiling water bath for 6 and 5 mins for each drug, respectively. Optimization of the different experimental conditions were studied. The mean percentage recoveries were found to be 100.73 ± 0.87% & 100.73 ± 0.44%, respectively. The method was applied successfully for the determination of some pharmaceutical formulations. The validity of the suggested procedure was assessed by applying the standard addition technique.

Determination of phenothiazines by charge-transfer complex formation with chloranilic acid

A rapid and sensitive spectrophotometrc method has been developed for the microdetermination of some phenothiazine derivatives as the pure substances and in different dosage forms. The method depends on the formation of stable donor-acceptor complexes between phenothiazines and chloranilic acid in an acetonitrile-2-propanol solvent mixture. The resulting intensely purple chloranilic acid radical anion possesses a characteristic absorption maximum at 515 nm. Beers law is obeyed over the concentration ranges 1-6, 1-10 and 5-30 mug ml for prochlorperazine dimaleate, trifluoperazine dihydrochloride and thiethylperazine dihydrochloride, with apparent molar absorptivities of 7.76 x 10(4), 1.95 x 10(4) and 6.64 x 10(3) 1. mole(-1).cm(-1), respectively. Statistical comparison of the results with those of an official method shows excellent agreement and indicates no significant difference in precision.

Synchronous fluorescence spectrofluorimetric method for the simultaneous determination of metoprolol and felodipine in combined pharmaceutical preparation

A rapid, simple and sensitive synchronous specrtofluorimetric method has been developed for the simultaneous analysis of binary mixture of metoprolol (MTP) and felodipine (FDP). The method is based upon measurement of the synchronous fluorescence intensity of the two drugs at Δλ of 70 nm in aqueous solution. The different experimental parameters affecting the synchronous fluorescence intensities of the two drugs were carefully studied and optimized. The fluorescence intensity-concentration plots were rectilinear over the ranges of 0.5-10 μg/mL and 0.2-2 μg/mL for MTP and FDP, respectively. The limits of detection were 0.11 and 0.02 μg/mL and quantification limits were 0.32 and 0.06 μg/mL for MTP and FDP, respectively. The proposed method was successfully applied for the determination of the two compounds in their commercial tablets and the results obtained were favorably compared to those obtained with a comparison method.

Simultaneous determination of sulpiride and mebeverine by HPLC method using fluorescence detection: application to real human plasma

A new simple, rapid and sensitive reversed-phase liquid chromatographic method was developed and validated for the simultaneous determination of sulpiride (SUL) and mebeverine Hydrochloride (MEB) in the presence of their impurities and degradation products. The separation of these compounds was achieved within 6 min on a 250 mm, 4.6 mm i.d., 5 m particle size Waters®-C18 column using isocractic mobile phase containing a mixture of acetonitrile and 0.01 M dihydrogenphosphate buffer (45:55) at pH = 4.0. The analysis was performed at a flow rate of 1.0 mL/min with fluorescence-detection at excitation 300 nm and emission at 365 nm. The concentration-response relationship was linear over a concentration range of 10- 100 ng/mL for both MEB and SUL with a limit of detection 0.73 ng/mL and 0.85 ng/mL for MEB and SUL respectively. The proposed method was successfully applied for the analysis of both MEB and SUL in bulk with average recoveries of 100.22 ± 0.757% and 99.96 ± 0.625% respectively, and in commercial tablets with average recoveries of 100.04 ± 0.93% and 100.03 ± 0.376% for MEB and SUL respectively. The proposed method was successfully applied to the determination of MEB metabolite (veratic acid) in real plasma simultaneously with SUL. The mean% recoveries (n = 3) for both MEB metabolite (veratic acid) and SUL were 100.36 ± 2.92 and 99.06 ± 2.11 for spiked human plasma respectively. For real human plasma, the mean% recoveries (n = 3) were and respectively.

Spectrophotometric Studies On Determination of Some Cephalosporins and Amoxycillin With Chlorobenzotriazole and Sodium Hypochlorite

Abstract Two simple colorimetric methods for the determination of certain cephalosporins (cefaclor and cefadroxil) and amoxycillin sodium are described. The suggested methods depend upon the oxidation of these compounds using sodium hypochlorite (SHC) and 1-chlorobenzotriazole (1-CBT) in alkaline medium and colorimetric measurment of the chromophore formed. The different experimental parameters are studied and incorporated into the procedures. The mean percentages found range from 100.0 ± 0.4 to 100.5 ± 0.9. The proposed methods have been successfully applied to the analysis of some pharmaceutical formulations and the results obtained have been statistically compared with those obtaind using the official methods. The proposed methods are convenient, rapid within the concentration range 15-123 μg. ml−1.

Microemulsion Liquid Chromatographic Determination of Nicardipine Hydrochloride in Pharmaceutical Preparations and Biological Fluids. Application to Stability Studies

Abstract A simple, stability indicating, reversed phase high performance liquid chromatographic method has been developed for the determination of nicardipine hydrochloride (NC) in the presence of its degradation products. Reversed phase chromatography was conducted using a Hibar‐C18 (150×4.6 mm i.d.) stainless steel column at ambient temperature with UV‐detection at 238 nm. Microemulsion mobile phase consisting of 0.175 M sodium dodecyl sulphate, 10% n‐propanol, 0.3% triethylamine in 0.02 M phosphoric acid of pH 6.5, has been used for the separation of nicardipine hydrochloride and its two degradation products at a flow rate of 1 mL min−1. The calibration curve was rectilinear over the concentration range 1‐40 µg mL−1 with a detection limit of 0.024 µg mL−1 (4.65×10−8 mol/L) and quantification limit of 0.08 µg mL−1 (1.55×10−7 mol/L). The proposed method was successfully applied for the analysis of nicardipine in pure form and commercial capsules, with the mean % recoveries of 100.12±0.28 and 100.87±0.41, respectively. The results obtained were favorably compared to those obtained by a reference method. The method was extended to the in‐vitro determination of NC in spiked human plasma samples with the mean % recovery of 100.33±3.06 (n=3). Moreover, the method was utilized to investigate the kinetics of both alkaline induced degradation and photo degradation of the drug. The apparent first‐order rate constant, half‐life time, and activation energy of the degradation product were calculated.

Spectrophotometric determination of loperamide hydrochloride by acid-dye and charge-transfer complexation methods in the presence of its degradation products

Two simple, sensitive and accurate spectrophotometric methods for the determination of loperamide hydrochloride (lop. HCl) are described. The first method is based on the formation of ion-pair association complex (1:1) with bromothymol blue (BTB), bromophenol blue (BPB) and naphthol blue black B (NBB). The coloured products are extracted into chloroform, and measured spectrophotometrically at 414 (BTB), 415 (BPB) and 627 nm (NBB). Beers law was obeyed in the ranges of 5-35, 5-30 and 0.8-11.2 microg ml(-1) for BTB, BPB and NBB methods, respectively. The method was found to be specific for the analysis of the drug in presence of its degradation products which can be detected by HPLC procedure. The second method is based on the reaction of the basic loperamide with iodine in chloroform to give molecular charge-transfer complex with intense bands at 295 and 363 nm. Beers law was obeyed in the ranges 2.5-17.5 and 2.5-22.5 microg ml(-1) for the method at 295 and 363 nm, respectively. Optimization of the different experimental conditions are described for both methods. The proposed methods have been applied successfully for the analysis of the drug in pure form and in its dosage forms. The methods have the advantage of being highly sensitive and simple for the determination of a small dose drug, which is also a weak UV-absorbing compound.

Spectrophotometric determination of piperazine via charge-transfer complexes

Iodine-piperazine or chloranil-piperazine charge-transfer complexes have been used for the sensitive assay of piperazine or its salts; these complexes exhibit intense absorption bands in the electronic spectrum. The molecular ratios of the reactants in the complexes have been established and the experimental conditions leading to maximum charge-transfer bands were also studied. The proposed procedures have been applied successfully to pure samples and drug formulations with good accuracy. The average recovery was 100.26–100.84% with piperazine-iodine and 99.33–100.33% with piperazine-chloranil charge-transfer complexes, with an average standard deviation for each method of 0.8–3.9%.