Mohamed Rizk

Capillary Electrophoretic Determination of Antimigraine Formulations Containing Caffeine, Ergotamine, Paracetamol and Domperidone or Metoclopramide

A novel, fast, sensitive and specific technique using capillary electrophoresis coupled to a diode array detector has been developed for the separation and simultaneous determination of two antimigraine mixtures in tablet formulation. The two combinations are ergotamine tartrate (ERG), caffeine (CAF) and paracetamol (PAR) with either domperidone (DOM), combination (I) or metoclopramide (MET), combination (II). The proposed method utilized a fused silica capillary (55 cm × 75 µm i.d.) and background electrolyte composed of phosphate buffer (25 mM, pH 9.8). The separation was achieved at 20 KV applied voltage and at 25°C. The described method was linear over the range of 1-80 and 2-100 µg/mL for CAF and MET, respectively, and 1-80 µg/mL for DOM, ERG and PAR. Intra-day and inter-day relative standard deviation (n = 5) was ≤1.10%. The limits of detection of CAF and PAR were 0.20 and 0.10 µg/mL, respectively, and 0.50 µg/mL for MET, DOM and ERG. Other aspects of analytical validation were also evaluated. The proposed method was successfully applied to the analysis of the two combinations in their tablets. Therefore, the proposed method is suitable for the routine control of these ingredients in multicomponent dosage forms.

Development and Validation of a Stability-Indicating Micellar Liquid Chromatographic Method for the Determination of Timolol Maleate in the Presence of Its Degradation Products

A stability-indicating micellar liquid chromatographic (MLC) method was developed and validated for the quantitative determination of timolol maleate (TM) in the presence of its degradation products resulting from accelerated degradation in a run time not more than 8 min. TM was subjected to stress conditions of hydrolysis (including alkaline, acidic and thermal hydrolysis) and oxidation. An isocratic, rapid and mobile phase saving the micellar LC method was developed with a BioBasic phenyl column (150 × 1.0 mm, 5 µm particle size) and a micellar mobile phase composed of 0.1 M sodium dodecyl sulfate, 10% of 1-propanol and 0.1% of triethylamine in 0.035 M ortho-phosphoric acid. The flow rate of the mobile phase was 0.1 mL/min. UV detection was adjusted at 298 nm and performed at room temperature. The method has been validated according to the International Conference on Harmonisation guidelines. The method is successfully applied for the determination of TM in bulk powder and pharmaceutical dosage form.

Simultaneous Determination of Atenolol and Nifedipine by UsingSpectrophotometric Method with Multivariate Calibration and HPLCMethod Implementing âÂÂDesign of ExperimentâÂÂ

Objectives: The aim of the present work is to develop rapid and simple methods for the simultaneous determination of atenolol and nifedipine. Multivariate calibration using preprocessing methods to enhance results in case of presence of any interference in samples and RP-HPLC method for achieving a good separation with accepted system suitability parameters with the use of design of experiment for robustness testing according to Plackett-Burman design. Methods: The spectrophotometric method is based on the measurement of the mixture in the range of 200-400 nm then applies the multivariate calibration methods for resolution of the binary mixture mainly using partial least squares (PLS) and principal component regression (PCR). The proposed RP-HPLC method utilizes an YMC-pack pro C18 column (250 mm x 4.6 mm, 5 μm). Optimum chromatographic conditions were attained by application of Design of experiment (DOE). Both spectrophotometric and chromatographic methods were applied on the determination of both drugs in marketed capsules. Also, dissolution testing of these capsules was investigated. Results: The recovery percentage for nifedipine and atenolol in capsules dosage form were found to be in PLS method (100.50 ± 0.850, 100.78 ± 1.07), PCR method (100.60 ± 0.960, 100.72 ± 1.09) and RP-HPLC method (99.77 ± 0.560, 100.90 ± 1.23); respectively. Conclusion: The methods were validated according to ICH guidelines. All the results obtained were found to be within the acceptable limits. The methods were successful to estimate nifedipine and atenolol in bulk powder and pharmaceutical preparation.

Simultaneous Determination of Timolol maleate and Brimonidine tartarate in their Pharmaceutical Dosage Form

Abstract Three new simple and selective assays were developed for the analysis of binary mixture containing timolol maleate (TM) and brimonidine tartarate (BT) in the presence of benzalkonium chloride (BZ) as a preservative in eye drops. The first derivative ultraviolet spectrophotometry was used with zero-crossing measurements at 313 nm for TM and 386 nm for BT, respectively. The second method depends on the first derivative of the ratio spectra with zero-crossing measurements at 313 nm and 391 nm for TM and BT, respectively using 0.25 µg/mL BZ as a divisor. The assays were linear over the concentration ranges 5–85 µg/ mL and 2–35 µg/mL for TM and BT, respectively. The third method was based on isocratic and mobile phase saving micellar liquid chromatographic method with a Biobasic phenyl column (150 x 1.0 mm, 5 µm particle size) and micellar mobile phase composed of 0.1M SDS, 10 % of 1-propanol and 0.1 % of TEA in 0.035M ortho phosphoric acid. UV detection was adjusted at 298 nm and 250 nm for TM and BT, respectively performed at room temperature. The linearity range for TM and BT was 2–100 µg/mL and 1–50 µg/mL, respectively. The proposed methods showed high percentage recovery, good accuracy and precision.

Validated stability-indicating HPLC method for the determination of mesna in presence of its degradation products.

A rapid and simple stability-indicating liquid chromatographic method was developed and validated for analysis of mesna in the presence of its degradation products in drug substance and drug products in a run time not >5 min. The separation was achieved on a RP amide C16 column at room temperature using methanol-phosphate buffer (10:90, v/v, pH 3.0) as mobile phase at a flow rate of 1 mL min(-1) and UV detection at 210 nm. The detector response for mesna was linear over the selected concentration range from 50 to 1000 µg mL(-1) with a correlation coefficient 0.9998. The limit of detection and the limit of quantitation were 7.5 and 22.7 µg mL(-1), respectively. The solution was stable for at least 5 days. Baseline resolution between mesna and its degradation products was achieved. Diode array detection peak purity tests showed no peak interfered with mesna peak. Moreover, the method was successfully applied for the determination of mesna in two different commercially available drug products.

Stability-Indicating Chromatographic Methods for Determination of Agomelatine in Drug Substance and Drug Product

Three sensitive and validated chromatographic methods were developed for determination of Agomelatine (AGO) in the presence of its degradation products in drug substance and drug product. The first and second methods were normal thin layer chromatographic (NP-TLC) and reversed phase thin layer chromatographic (RP-TLC) methods. Mobile phase consisting of ethyl acetate-ammonia (33%)-methanol (8.5:0.5:1, v/v/v) was used for NP-TLC while for RP-TLC using 0.1% triethylamine (TEA): acetonitrile (60:40 v/v) at pH=2. The chromatograms were scanned at 230 and 280 nm and determined in the range of 0.1-4 and 0.3-4 μg/spot with mean percentage recovery of 99.89 ± 1.141 and 100.01 ± 1.062 for NP-TLC and RP-TLC respectively. The third method was Micellar Liquid Chromatographic (MLC) method using C18 column and a mobile phase consisting of 0.1 M Sodium Dodecyl Sulphate (SDS), 15% butan-1-ol, 0.2% TEA in water adjusted to pH=3. The UV detection was achieved at 230 nm and determined in the range of 0.5-5 μg/mL with mean percentage recovery of 100.13 ± 0.970. The proposed methods were successfully applied as stability indicating methods under different stressed conditions according to the International Conference of Harmonization (ICH) guidelines. The methods showed good selectivity, repeatability, linearity and sensitivity according to the evaluation of the validation parameters.

Sensitive validated voltammetric determination of apixaban using a multi-walled carbon nanotube-modified carbon paste electrode: application to a drug product and biological sample

A sensitive, accurate and precise voltammetric method was developed and validated for the determination of a selective factor Xa inhibitor apixaban in drug substances using a multi-walled carbon nanotube-modified carbon paste electrode (MWCNT/CPE). The electrochemical behaviour of apixaban showed an irreversible diffusion-controlled oxidation process at a potential of 1.21 V in neutralized phthalate buffer (pH 5.0). Various experimental conditions were investigated and optimized including pH, different buffer type, different electrode modifier, scan rate and different surfactant type. The diffusion coefficient was calculated using the chronoamperometric technique. The peak current varied linearly over the concentration ranges from 1.99 × 10−6 mol L−1 to 1.07 × 10−4 mol L−1 with correlation coefficients of 0.9996. The detection and quantitation limits were 6.81 × 10−7 mol L−1 and 1.99 × 10−6 mol L−1, respectively. The method was successfully applied for the determination of apixaban in a drug product and spiked plasma with recoveries (%) ± RSD of 100.28 ± 1.30% and 100.64 ± 1.22% respectively. The results obtained were found to be in good agreement with those obtained with the reference method of the investigated drug. The validity of the method was assessed according to ICH guidelines.