Dalia R. El-Wasseef

Synthesis and pharmacological evaluation of novel fused thiophene derivatives as 5-HT2A receptor antagonists: Molecular modeling study

Novel derivatives of cyclopentathienopyrimidinediones 6, pyridothienopyrimidinediones 7, ethyl cycloheptathiophene-3-carboxylates 10, ethyl tetrahydrothienopyridine-3-carboxylates 11, tetrahydrocycloheptathienopyrimidin-4(3H)-ones 12, tetrahydrotriazolobenzothienopyrimidin-5(4H)-ones 17 and tetrahydro-5H-cycloheptathienopyrimidin-4(3H)-ones 21 have been synthesized and tested for their 5-HT2A antagonist activity. Preliminary pharmacological studies showed that compounds 3-[2-[4-phenylpiperazin-1-yl]ethyl]-6,7-dihydro-5H-cyclopenta[b]thieno[2,3-d]pyrimidine-2,4(1H,3H)-dione 6a and ethyl 2-[[4-(2-methoxyphenyl)piperazin-1-yl]acetylamino]-4,5,6,7-tetrahydro-6-methylthieno[2,3-c]pyridine-3-carboxylate 11d were found to be the most active molecules as 5-HT2A antagonists. Molecular modeling and pharmacophore prediction methodology are used to study the structural features required for 5-HT2A antagonist properties of the active compounds compared with nonactive species by means of the molecular mechanic method. The 2-methoxy substituent in the structure of 11d seems to be necessary for its full antagonistic properties. Optimal placement of basic nitrogen relative to the plane of thiophene core was found to have a profound effect on affinity and biological activity.

Spectrofluorometric Determination of Drotaverine Hydrochloride in Pharmaceutical Preparations

Abstract A highly sensitive, spectrofluorometric method was developed for the determination of drotaverine HCl in pharmaceutical preparations. The proposed method is based on the measurement of the native fluorescence of the drug in 0.1 M H2SO4 at emission 465 nm after excitation at 295 nm. The relative fluorescence intensity-concentration plot was rectilinear over the range of 0.16–4 µg·ml−1, with good correlation (r = 0.9999) and a lower limit of detection (LOD) of 0.032 µg·ml−1. The proposed method was successfully applied for the determination of drotaverine HCl in tablets and ampoules with a recovery percentage of 100.42 ± 0.601,99.83 ± 0.82 and 99.43 ± 1.08, respectively, which were in accordance with those obtained by a compendial method.

Spectrophotometric and spectrofluorimetric determination of indacaterol maleate in pure form and pharmaceutical preparations: application to content uniformity.

Two simple, rapid, sensitive and precise spectrophotometric and spectrofluorimetric methods were developed for the determination of indacaterol maleate in bulk powder and capsules. Both methods were based on the direct measurement of the drug in methanol. In the spectrophotometric method (Method I) the absorbance was measured at 259 nm. The absorbance-concentration plot was rectilinear over the range 1.0-10.0 µg mL(-1) with a lower detection limit (LOD) of 0.078 µg mL(-1) and lower quantification limit (LOQ) of 0.238 µg mL(-1). Meanwhile in the spectrofluorimetric method (Method II) the native fluorescence was measured at 358 nm after excitation at 258 nm. The fluorescence-concentration plot was rectilinear over the range of 1.0-40.0 ng mL(-1) with an LOD of 0.075 ng mL(-1) and an LOQ of 0.226 ng mL(-1). The proposed methods were successfully applied to the determination of indacaterol maleate in capsules with average percent recoveries ± RSD% of 99.94 ± 0.96 for Method I and 99.97 ± 0.81 for Method II. In addition, the proposed methods were extended to a content uniformity test according to the United States Pharmacopoeia (USP) guidelines and were accurate, precise for the capsules studied with acceptance value 3.98 for Method I and 2.616 for Method II.

Microemulsion liquid chromatographic method for simultaneous determination of simvastatin and ezetimibe in their combined dosage forms.

A rapid HPLC procedure using a microemulsion as an eluent was developed and validated for analytical quality control of antihyperlipidemic mixture containing simvastatin (SIM) and ezetimibe (EZT) in their pharmaceutical preparations. The separation was performed on a column packed with cyano bonded stationary phase adopting UV detection at 238 nm using a flow rate of 1 mL/min. The optimized microemulsion mobile phase consisted of 0.2 M sodium dodecyl sulphate, 1% octanol, 10% n-propanol, and 0.3% triethylamine in 0.02 M phosphoric acid at pH 5.0. The developed method was validated in terms of specificity, linearity, lower limit of quantification (LOQ), lower limit of detection (LOD), precision, and accuracy. The proposed method is rapid (8.5 min), reproducible (RSD < 2.0%) and achieves satisfactory resolution between SIM and EZT (resolution factor = 2.57). The mean recoveries of the analytes in pharmaceutical preparations were in agreement with those obtained from a reference method, as revealed by statistical analysis of the obtained results using Students t-test and the variance ratio F-test.

Spectrofluorimetric determination of two β-agonist drugs in bulk and pharmaceutical dosage forms via derivatization with dansyl chloride

A sensitive, simple and rapid spectrofluorimetric method has been developed for the determination of both Fenoterol hydrobromide (FNT) and Ritodrine hydrochloride (RTH) in pure and dosage forms. The method is based on derivatization using dansyl chloride (DNS-Cl) as fluorogenic agent and measuring the fluorescence of the products at emission wavelengths of 517 and 515 nm after excitation at 348 and 343 nm for FNT and RTH, respectively. Different experimental parameters affecting the fluorescence intensities were carefully studied and optimized. The relation between fluorescence intensities and drug concentrations were rectilinear over the concentration range of 0.25–6.0 μg/mL for both drugs with a minimum detectability of 0.065 and 0.045 μg/mL for FNT and RTH, respectively. The percentage recoveries ±SD were 100.1 ± 0.9, 99.9 ± 0.6 for FNT and RTH respectively. The proposed method was successfully applied to the determination of both drugs in their commercial dosage forms. The obtained results were statistically validated and agreed well with those obtained with reference methods. A suggestion for the reaction pathway with DNS-Cl was postulated.

SIMULTANEOUS IN VITRO HPLC DETERMINATION OF ENALAPRIL MALEATE AND LERCANIDIPINE HCL

A reversed-phase liquid chromatographic (RP-HPLC) method was developed for the simultaneous determination of a binary mixture of enalapril maleate and Lercanidipine HCl in pure form, synthetic mixture, and synthetic tablets. The analysis was carried out using Hibar® C18, pre-packed column. Mobile phase, containing acetonitrile:methanol:water:orthophosphoric acid (35:35:30:0.2) adjusted to pH 3.0 with triethylamine, was pumped at a flow rate of 1.0 mL min−1 with UV-detection at 210 nm. The method showed good linearity in the range of 5.0–100.0 μg mL−1 for both drugs. The detection limit of the proposed method was 0.80 and 0.93 μg mL−1, and the quantitation limit was 2.42 and 2.80 μg mL−1 for ENM and LER, respectively.

Multiobjective optimization strategy based on desirability functions used for the microemulsion liquid chromatographic separation and quantification of norfloxacin and tinidazole in plasma and formulations

The aim of the present study was to optimize a microemulsion liquid chromatography method for the simultaneous determination of norfloxacin and tinidazole binary mixture using a chemometric protocol. Optimization experiments were conducted through a process of screening and optimization. A 2(7-4) fractional factorial design was used as screening design. While the location of optimum conditions was established by applying Derringers desirability function. The optimal mobile phase composition was predicted to be: 3.5% w/v SDS, 10.03% v/v 1-propanol, 0.5% v/v 1-octanol, and 0.3% triethylamine in 0.02 M phosphoric acid at pH 6.5. The mobile phase was delivered isocratically at a flow rate of 1 mL/min with UV detection at 290 nm. Tinidazole and norfloxacin were eluted with retention times of 1.8 and 5.8 min, respectively. The calibration plots displayed good linear relationships in the concentration ranges of 0.5-50 and 0.75-75 μg/mL for norfloxacin and tinidazole, respectively. The method was successfully applied for determination of both drugs in pharmaceutical dosage forms and real human plasma. Where the accuracy was proved by the low values of % error and high values of recovery, also the relative standard deviation for the results did not exceed 1.5%, proving the precision of the method.

Simultaneous Determination of Enalapril and Hydrochlorothiazide in Pharmaceutical Preparations Using Microemulsion Liquid Chromatography

A rapid high-performance liquid chromatography procedure for analytical quality control of mixture containing enalapril maleate (ENM) and hydrochlorothiazide (HCT) in their pharmaceutical preparations was developed using a microemulsion as an eluent. The separation was performed on a column packed with cyano-bonded stationary phase adopting UV detection at 210 nm using a flow rate of 1 mL/min. The optimized microemulsion mobile phase consisted of 0.2 M sodium dodecyl sulfate, 1% octanol, 10% n-propanol and 0.3% triethylamine in 0.02 M phosphoric acid, and pH was adjusted at 3.5. The proposed method was found to be linear over the concentration ranges 1-100 and 0.05-5 μg/mL for ENM and HCT, respectively with a correlation coefficient of 0.9999 for both drugs. The developed method was validated in terms of specificity, linearity, lower limit of quantification, lower limit of detection, precision and accuracy. The proposed method is rapid (5 min), reproducible (relative standard deviation <2.0%) and achieves a satisfactory resolution between ENM and HCT (resolution factor = 3.62). The mean recoveries of the analytes in tablets were in agreement with those obtained from a comparison method, as revealed by statistical analysis of the obtained results using Students t-test and the variance ratio F-test.

SIMULTANEOUS DETERMINATION OF RITODRINE AND ISOXSUPRINE IN PHARMACEUTICAL PREPARATIONS USING LIQUID CHROMATOGRAPHY

Simultaneous determination of two structurally related ß2 adrenergic receptor agonists namely, Ritodrine HCl (RTH) and Isoxsuprine HCl (ISP) was performed using reversed phase HPLC. The separation was performed on a C18 column adopting UV detection at 221 nm using a flow rate of 1 mL/min. The mobile phase consisted of acetonitrile: methanol: acid phosphate buffer (25:25:50) pH 4.5. The developed method was validated in terms of specificity, linearity, lower limit of quantification, lower limit of detection, precision, and accuracy. With the proposed method, satisfactory resolution between the two drugs was obtained (resolution factor = 2.76). Linear determination range of both drugs was 1–100 µg/mL. The proposed method was applied to the determination of RTH and ISP in synthetic mixtures and pharmaceutical samples. The method requires a minimum of sample handling and is rapid (within 3 min) and reproducible (RSD < 2.0%). The mean recoveries of the analytes in pharmaceutical preparations were in agreement with those obtained from reference methods, as revealed by statistical analysis of the obtained results using the Students t-test and the variance ratio F-test.

Spectrofluorometric Determination of Cephalexin in Pharmaceutical Preparations and Spiked Human Urine Using 2‐Cyanoacetamide

Abstract A simple, accurate, sensitive, and validated method was developed for the spectrofluorometric determination of cephalexin. The method involves the reaction of cephalexin with 2‐cyanoacetamide in presence of 33% ammonia solution. The formed fluorescent product exhibited maximum fluorescence intensity at λ 439 nm, after excitation at λ 339 nm. Different experimental parameters affecting the derivatization reaction were carefully studied and incorporated in the procedure. Under the described conditions, the proposed method was linear over the concentration range 0.04–0.4 µg/mL. The average percent found was 99.6±0.9%. The LOD was 7.76 ng/mL. The proposed method was applied for determination of cephalexin in pharmaceutical preparations as well as in spiked human urine. A mechanism of the reaction is postulated.