Wafaa S. Hassan

Spectrophotometric determination of etodolac in pure form and pharmaceutical formulations

BackgroundEtodolac (ETD) is a non-steroidal anti-inflamatory antirheumatic drug. A survey of the literature reveals that there is no method available for the determination of ETD in pure form and pharmaceutical formulations by oxidation-reduction reactions.ResultsWe describe three simple, sensitive and reproducible spectrophotometric assays (A-C) for the determination of etodolac in pure form and in pharmaceutical formulations. Methods A and B are based on the oxidation of etodolac by Fe3+ in the presence of o-phenanthroline (o-phen) or bipyridyl (bipy). The formation of the tris-complex on reaction with Fe3+-o-phen and/or Fe3+-bipy mixtures in acetate buffer solution at optimum pH was demonstrated at 510 and 520 nm with o-phen and bipy. Method C is based on the oxidation of etodolac by Fe3+ in acidic medium, and the subsequent interaction of iron(II) with ferricyanide to form Prussian blue, with the product exhibiting an absorption maximum at 726 nm. The concentration ranges are 0.5–8, 1.0–10 and 2–18 μg mL-1 respectively for methods A, B and C. For more accurate analysis, Ringbom optimum concentration ranges were calculated, in addition to molar absorptivity, Sandell sensitivity, detection and quantification limits.ConclusionOur methods were successfully applied to the determination of etodolac in bulk and pharmaceutical formulations without any interference from common excipients. The relative standard deviations were ≤ 0.76 %, with recoveries of 99.87 % – 100.21 %.

Spectophotometric methods for determination of cefdinir in pharmaceutical formulations via derivatization with 1,2-naphthoquinone-4-sulfonate and 4-chloro-7-nitrobenzo-2-oxa-1, 3-diazole

Two new simple, sensitive, accurate, and precise spectrophotometric methods have been developed and validated for the determination of cefdinir (CFD) in bulk drug and in its pharmaceutical formulations. The first method was based on the reaction of CFD with 1, 2- napthaquinone-4- sulfonic acid sodium (NQS) in an alkaline medium (pH 11) to form an orange-coloured product that was measured at 490 nm. The second method depends on hydrolysis of CFD using 0.5 M NaOH at 100 °C and subsequent reaction of the formed sulfide ions with 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) to form a yellow-coloured chromogen measured at 390 nm. Different variables affecting the reactions of CFD with both NQS and NBD-Cl (e.g. NaOH concentration, hydrolysis time, NQS or NBD-Cl concentration and diluting solvent) were studied and optimized. Under optimum conditions, good linear relationships with good correlation coefficients (0.9990-0.9999) were found in the range of 10-80 and 5.0-30 µg ml(-1) for NQS and NBD-Cl, respectively. The limits of assay detection and quantitation ranged from 1.097 and 0.280 and 3.656 and 0.934 µg ml(-1) for NQS and NBD-Cl, respectively. The accuracy and precision of the proposed methods were satisfactory. The proposed method is simple, rapid, precise and convenient and was successfully applied for analysis of CFD in its pharmaceutical formulations and the recovery percentages ranged from 99.25 to 100.20%.

DEVELOPMENT AND VALIDATION OF A RAPID STABILITY INDICATING CHROMATOGRAPHIC DETERMINATION OF CEFDINIR IN BULK POWDER AND DOSAGE FORM USING MONOLITHIC STATIONARY PHASE

A simple, rapid, and accurate, routine-HPLC method is described for quantitation of Cefdinir in bulk powder and dosage form. The chromatographic separation was carried out on Chromolith Performance RP-18e column, a relatively new packing material consisting of monolithic rods of highly porous silica, using isocratic binary mobile phase of MeOH and 25 mM KH2PO4 pH 3.0 in the ratio of 10:90 at flow rate of 5 mL/min and 40°C. A diode array detector was used at 214 nm for detection. The elution time of Cefdinir was found to be 2.183 ± 0.003 minutes. The method was validated for system suitability, linearity, precision, limits of detection and quantitation, specificity, stability, and robustness. The robustness study was done for small changes in KH2PO4 concentration and pH, temperature, flow rate, wavelength of detection, % of MeOH in mobile phase, and injection volume. Stability tests were done through exposure of the analyte solution for four different stress conditions: Reflux with 1 N HCl, reflux with 1 N NaOH, reflux with 30% H2O2 and exposure to UV radiation. The limits of detection and quantification were 0.313 and 0.625 µgmL−1, respectively. The recovery value of this method was 98.00% and the reproducibility was within 2.98.

New Spectrophotometric and Conductometric Methods for Macrolide Antibiotics Determination in Pure and Pharmaceutical Dosage Forms Using Rose Bengal

Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation of erythromycin thiocyanate (I), clarithromycin (II), and azithromycin dihydrate (III) in both pure and pharmaceutical dosage forms. The spectrophotometric procedure depends on the reaction of rose bengal and copper with the cited drugs to form stable ternary complexes which are extractable with methylene chloride, and the absorbances were measured at 558, 557, and 560 nm for (I), (II), and (III), respectively. The conductometric method depends on the formation of an ion-pair complex between the studied drug and rose bengal. For the spectrophotometric method, Beers law was obeyed. The correlation coefficient () for the studied drugs was found to be 0.9999. The molar absorptivity (), Sandell’s sensitivity, limit of detection (LOD), and limit of quantification (LOQ) were also calculated. The proposed methods were successfully applied for the determination of certain pharmaceutical dosage forms containing the studied drugs

SPECTROPHOTOMETRIC AND FLUORIMETRIC METHODS FOR DETERMINATION OF NALTREXONE IN URINE, SERUM AND TABLETS BY OXIDATION WITH CERIUM (IV)

This paper proposes new methods for simple and sensitive spectrophotometric and fluorimetric determination of naltrexone (NALT) in tablet and biological fluids. The spectrophotometric method involve addition of a known excess of Ce(IV) to NALT in acid medium, followed by determination of residual Ce(IV) by reacting with a fixed amount of methyl orange, and measuring the absorbance at 510 nm. Fluorimetric method was based on the oxidation of NALT with Ce(IV) to produce Ce(III) and its fluorescence was monitored at 350 nm after excitation at 250 nm. In both methods, the amount of Ce(IV) reacted corresponds to the amount of NALT and the measured absorbance or fluorescence were found to increase linearly with the concentration of NALT, which are corroborated by the correlation coefficients of 0.9999 and 0.9996 for spectrophotometric and fluorimetric methods, respectively. Different variables affecting the reaction conditions such as the concentrations of Ce(IV), type and concentration of acid medium, reaction time, temperature, and the diluting solvents were carefully studied and optimized. 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 NALT in pharmaceutical formulation and biological samples with good recoveries.

Investigation of anti-Hepatitis C virus, sofosbuvir and daclatasvir, in pure form, human plasma and human urine using micellar monolithic HPLC-UV method and application to pharmacokinetic study

Simultaneous determination of sofosbuvir (SOF), and daclatasvir (DAC) in their dosage forms, human urine and human plasma using simple and rapid micellar high performance liquid chromatographic method coupled with UV detection (HPLC-UV) had been developed and validated. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of Hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. Separation and quantitation were carried out on anonyx™ C8 monolithic (100 × 4.6 mm (i.d.) analytical column maintained at 25 °C. The mobile phase consisted of 0.1 M sodium dodecyl sulfate (SDS) solution containing 20% (V/V) n-propanolol and 0.3% (V/V) triethylamine and pH was adjusted to 6.5 using 0.02 M phosphoric acid, respectively. The retention times of SOF and DAC were 4.8 min, and 6.5 min, respectively. Measurements were made at flow rate of 0.5 mL/min with injection volume of 20 μL and ultraviolet (UV) detection at 226 nm. Linearity of SOF and DAC was obtained over concentration ranges of 50-400, and 40-400 ng/mL, respectively in pure form, 60-300 and 50-300 ng/mL, respectively for human plasma and over 50-400, and 40-400 ng/mL, respectively for human urine with correlation coefficient >0.999. The proposed method demonstrated excellent intra- and inter-day precision and accuracy. The suggested method was applied for determination of the drugs in pure, dosage form, and in real human plasma, real human urine and drug-dissolution test of their tablets. The obtained results have been statistically compared to reported method to give a conclusion that there is no significant differences.

Comparative study of six sequential spectrophotometric methods for quantification and separation of ribavirin, sofosbuvir and daclatasvir: An application on Laboratory prepared mixture, pharmaceutical preparations, spiked human urine, spiked human plasma, and dissolution test

In accordance with International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, six novel, simple and precise sequential spectrophotometric methods were developed and validated for the simultaneous analysis of Ribavirin (RIB), Sofosbuvir (SOF), and Daclatasvir (DAC) in their mixture without prior separation steps. These drugs are described as co-administered for treatment of Hepatitis C virus (HCV). HCV is the cause of hepatitis C and some cancers such as liver cancer (hepatocellular carcinoma) and lymphomas in humans. These techniques consisted of several sequential steps using zero, ratio and/or derivative spectra. DAC was first determined through direct spectrophotometry at 313.7 nm without any interference of the other two drugs while RIB and SOF can be determined after ratio subtraction through five methods; Ratio difference spectrophotometric method, successive derivative ratio method, constant center, isoabsorptive method at 238.8 nm, and mean centering of the ratio spectra (MCR) at 224 nm and 258 nm for RIB and SOF, respectively. The calibration curve is linear over the concentration ranges of (6-42), (10-70) and (4-16) μg/mL for RIB, SOF, and DAC, respectively. This method was successfully applied to commercial pharmaceutical preparation of the drugs, spiked human urine, and spiked human plasma. The above methods are very simple methods that were developed for the simultaneous determination of binary and ternary mixtures and so enhance signal-to-noise ratio. The method has been successfully applied to the simultaneous analysis of RIB, SOF, and DAC in laboratory prepared mixtures. The obtained results are statistically compared with those obtained by the official or reported methods, showing no significant difference with respect to accuracy and precision at p = 0.05.

Validated Stability-Indicating Methods for Determination of Mometasone Furoate in Presence of its Alkaline Degradation Product

Two novel stability-indicating TLC densitometric and chemometric methods were developed for the determination of mometasone furoate (MF) in the presence of its alkaline degradation product (MF Deg). The developed TLC densitometric method (Method A) is based on the quantitative densitometric separation of MF from its alkaline degradation product on silica gel 60 F254 and measurement of the bands at 250 nm. The separation was carried out using hexane-chloroform-methanol-acetonitrile (6:6:1:0.3, by volume) as a developing system. A well-resolved and compact bands for (MF) and (MF Deg) at retention factors 0.36 and 0.66, respectively. Good resolution between (MF) and (MF Deg) assured the specificity of the proposed method. The method showed good linearity in the concentration range 0.5-5 μg/band with r2 = 0.9998. The method validation was performed according to ICH guidelines demonstrating to be accurate, precise, robust and sensitive. The LOD and LOQ were found to be 0.21 and 0.63 μg/band for MF, respectively. The developed TLC-densitometric method can be applied for identification and quantitative determination of MF in bulk drug and pharmaceutical dosage forms without any interference from excipients and degradates. Method B is a multivariate chemometric-assisted spectrophotometry, where classical least squares, principal component regression and partial least squares were applied. Statistical analysis of the results has been carried out revealing high accuracy and good precision.

Simple Spectrophotometric and Conductometric methods for Determination of Gemifloxacin in Pure, Pharmaceutical Dosage Form and Human Urine

Article history: Received on: 17/09/2015 Revised on: 09/01/2016 Accepted on: 03/03/2016 Available online: 28/12/2016 Two Simple, accurate, precise, and rapid spectrophotometric and conductometric methods were developed for the estimation ofgemifloxacin (GEM) in pharmaceutical dosage forms and biological human urine. Method A: A spectrophotometric method is based on the oxidation reaction between phosphomolybdic acid (PMA) and GEM to form molybdenum blue (Mo +5 ). Beer , s law was obeyed in the concentration range of (5-27 μg/ml). The correlation coefficient ( 2) for the studied drug was found to be 0.9999. The molar absorptivity ( ), Sandells sensitivity, limit of detection (LOD), and limit of quantitation (LOQ)were also calculated. Method B: A conductometric method is based on formation of an ion associate with PMA. It involves direct titration with PMA in the range of 1-20 mg. The precipitate obtained by ion pairing GEM with PMA has been spectroscopically characterized using IR spectroscopy. The method was successively applied to pharmaceutical formulations containing GEM. The results obtained were favorably compared with those obtained using the reported method.

Application of non-steroidal anti-inflammatory drugs for palladium determination

A highly sensitive spectrophotometric method for palladium determination using piroxicam and tenoxicam as new chromogenic reagents has been developed. In the presence of sodium lauryl sulfate (SLS), palladium reacts with piroxicam (PX) or tenoxicam (TX) to form stable yellow orange complexes in an acetate buffer solution of pH 5.0 at 424 nm and 426 nm with molar absorptivity of 7.16 × 104 L mol−1 cm−1 and 1.20 × 105 L mol−1 cm−1, respectively. Sandell sensitivity, detection, and quantitation limits were also calculated. Optimum conditions were evaluated considering pH, reagent concentration, time, temperature, and surfactant concentration. The complex system conforms to Beer’s law over the range of 0.07–1.28 μg mL−1 palladium. The stoichiometric ratio and stability constant were also evaluated. Tolerance limits of many cations and anions were determined. Finally, the proposed method was applied successfully in the determination of palladium in jewellery, anode mud, synthetic mixtures, catalysts, and alloy samples.