M. A. Al-Omar

Rapid and sensitive simultaneous determination of ezetimibe and simvastatin from their combination drug products by monolithic silica high-performance liquid chromatographic column

A simple, precise and rapid high-performance liquid chromatography (HPLC) method has been developed and validated for the simultaneous determination of ezetimibe (EZE) and simvastatin (SIM) from their combination drug products. The applicability of monolithic LC phases in the field of quantitative analysis has been evaluated. The existing method with UV detection set at 240 nm was successfully transferred from a conventional silica column to a 10 cm x 4.6 mm i.d. monolithic silica column. By simply increasing the mobile phase flow rate, run time was about five-fold reduced and the consumption of mobile phase was about two-fold decreased, while the chromatographic resolution of the analytes remain unaffected. Ranitidine (RAN) was used as internal standard to guarantee a high level of quantitative performance. The method used a mobile phase consisted of acetonitrile-ammonium acetate (50 mM pH 5.0) (65:35, v/v). It was validated with respect to system suitability, specificity, limit of quantitation (LOQ) and detection (LOD), linearity, precision, accuracy, and recovery, respectively. The described method was linear over the range of 40-1200 ng ml(-1) (r=0.999) for both drugs. The LOD for EZE and SIM were 13.2+/-0.4029 and 13.3+/-0.4772 ng ml(-1), respectively. The LOQ were found to be 39.9+/-1.221 and 39.5+/-1.446 ng ml(-1) for EZE and SIM, respectively. The method is fast (less than 2.0 min) and is suitable for high-throughput analysis of the drug and ones can analyze 700 samples per working day, facilitating the processing of large-number batch samples.

Novel, selective sample stacking microemulsion electrokinetic capillary chromatography induced by reverse migrating pseudostationary phase for the determination of the new ultra-short acting hypnotic "HIE-124" in mice serum

Microemulsion electrokinetic capillary chromatography (MEEKC) with sample stacking induced by reverse migrating pseudostationary phase (SRMP) technique in a suppressed electro-osmotic flow (EOF) strategy was investigated for analysing the new ultra-short hypnotic HIE-124 in mice serum. The proposed method utilized fused-silica capillary with a total length of 50 cm (effective length 40 cm), applied voltages for stacking and separation were 5.0 kV for 4.30 min and subsequently 25 kV, respectively, with a sample injection of 0.5 psi for 90 s. All the runs were carried out at 25 degrees C and detected at 213 nm. The optimum microemulsion background electrolyte (BGE) solution consisted of 0.8% (v/v) ethyl acetate, 6.6% (v/v) butan-2-ol, 1.0% (v/v) acetonitrile, 2.0% (w/v) sodium dodecyl sulfate (SDS), and 89.6 mL with 25 mM phosphate buffer pH 8. When this preconcentration technique was used, the sample stacking and the separation processes took place successively with changing the voltage with an intermediate polarity switching step. The proposed method was validated carefully with respect to high specificity of the method, good linearity (r=0.9994), fair wide linear concentration range (66-1500 ng mL(-1)), limit of detection and quantitation were 21.6 and 65.5 ng mL(-1), respectively. The mean relative standard deviation (RSD) of the results of intra- and inter-day precision and accuracy were less than 6.0%, and overall recovery higher than 95% of HIE-124 in mice serum. The developed method could be used for the trace analyses of HIE-124 in serum and was finally used for the pharmacokinetic study investigation of HIE-124 in mice serum.

Electrochemical Studies and Square‐Wave Adsorptive Stripping Voltammetry of Spironolactone Drug

Abstract A sensitive and reliable stripping voltammetric method was developed to determine Spironolactone drug. This method is based on the adsorptive accumulation of the drug at a hanging mercury drop electrode and then a negative sweep was initiated, which yield a well defined cathodic peak at −1000 mV versus Ag/AgCl reference electrode. To achieve high sensitivity, various experimental and instrumental variables were investigated such as supporting electrolyte, pH, accumulation time and potential, drug concentration, scan rate, frequency, pulse amplitude, convection rate and working electrode area. The monitored adsorptive current was directly proportional to the concentration of Spironolactone and it shows a linear response in the range from 1×10−8 to 2.5×10−7 mol l−1 (correlation coefficient=0.999) and the detection limit (S/N=3) is 1.72×10−10 mol l−1 at an accumulation time of 90 sec. The developed AdSV procedure shows a good reproducibility, the relative standard deviation RSD% (n=8) at a concentration level of 1.5×10−7 mol l−1 was 1.4%, whereas the method accuracy was indicated via the mean recovery of 97.5%±2.04. Possible interferences by several substances usually present in the pharmaceutical formulations have been also evaluated. The applicability of this approach was illustrated by the determination of Spironolactone in pharmaceutical preparation and biological fluids such as serum and urine.

Synthesis, reactions, and antimicrobial activity of some novel fused thiazolo[3,2-a]pyrimidine-5H-indeno[1,2-d]pyrimidine derivatives

Series of novel substituted thioxopyrimidine and thiazolo[3,2-a]pyrimidine compounds that combine various heteroaryl rings have been synthesized via Biginelli one-pot three-component reaction and elucidated with chemical and spectral analysis. Several products were tested for their antimicrobial properties.

A Spectrophotometric Method for Diosmin Determination

A rapid and sensitive spectrophotometric method for the determination of diosmin (D) has been developed. The method is based on the reaction of D with 4-aminoantipyrine (AAP) in the presence of hexacyanoferrate (III) (HCF) in an alkaline medium and subsequent formation of a purple coloured product havingmax at 524.5 nm. The conditions affecting the reaction (reagents concentration, pH, order of addition of reagents, stability in time) were optimized. Under the optimum conditions, Beers law was obeyed in the range of 0.3 - 35 μg mL -1 D with a correlation coefficient of 0.9993. The assay limits of detection and quantitation were 0.1 and 0.3 μg mL -1 , respectively. The proposed method was successfully applied to the analysis of the drug tablets formulation. The results were compared favorably with those obtained by other reported methods.

Synthesis of chiral linear and macrocyclic candidates: VI. Synthesis and antibacterial activity of some macrocyclic tripeptides and linear dipeptide Schiff bases

A series of macrocyclic tripeptides and linear dipeptide Schiff base derivatives has been synthesized using pyridine-3,5-dicarboxylic acid and L-phenyalanine methyl ester as starting materials. Treatment of pyridine-3,5-dicarbonyl dichloride with L-phenylalanine methyl ester gave N,N′-(pyridine-3,5-diyldicarbonyl)bis(L-phenyalanine methyl ester) which was hydrolyzed with 1N sodium hydroxide to the corresponding bis-acid, and the latter was cyclized with diamino acids to afford macrocyclic tripeptide derivatives. The reaction of the bis ester with hydrazine hydrate gave bis-hydrazide, which was condensed with aldehydes to obtain the corresponding Schiff base derivatives. The structures of the newly synthesized compounds were confirmed by IR, 1H and 13C NMR, and MS spectral data and elemental analyses. The antimicrobial activities of some of the newly synthesized compounds were comparable with that of Streptomycin used as control.

Valproic Acid and Sodium Valproate: Comprehensive Profile

Publisher Summary This chapter focuses on valproic acid and sodium valproate. Valproic acid is a colorless to pale yellow, slightly viscous, clear liquid having a characteristic odor and slightly soluble in water. It is freely soluble in acetone, alcohol, chloroform, ether, benzene, n‐heptane, methyl alcohol, and 0.1 N sodium hydroxide that is slightly soluble in 0.1 N hydrochloric acid. Sodium valproate is a white or almost white, hygroscopic, crystalline, and deliquescent powder. Thermal methods of analysis and compendial methods of analysis are also described in the chapter. Valproic acid is found to be stable at room temperature. The refrigeration or freezing of a supernatant from blood samples containing the drug for 7 days does not alter the total concentration of valproic acid. Most of the reported methods of analysis of valproic acid and its sodium salt in biological fluids rely on the use of chromatography, especially gas chromatography, although high performance liquid chromatography (HPLC) is also reported. Other methods, as the flow injection analysis, enzyme‐immunoassay, fluorescence polarization capillary electrophoresis, and potentiometry are also used.

Ciprofloxacin: Drug Metabolism and Pharmacokinetic Profile

Publisher Summary Ciprofloxacin is commercially available as the monohydrate phase of its hydrochloride salt, and has been formulated for oral and ophthalmic administration. The compound has also been developed as the lactate salt for the use in intravenous administration. This chapter discusses the four active metabolites of ciprofloxacin— namely, desethyleneciprofloxacin, sulfo-ciprofloxacin, oxo-ciprofloxacin, and N-acetylciprofloxacin. Oxo-ciprofloxacin appears to be the major urinary metabolite, and sulfo-ciprofloxacin the primary fecal metabolite. The drug is partially metabolized in the liver by modification of the piperazinyl group. Oxo-ciprofloxacin and N-acetyl-ciprofloxacin microbial activities are comparable to norfloxacin, and desethylene-ciprofloxacin is comparable to nalidixic acid for certain organisms. Ciprofloxacin and its metabolite desethylene-ciprofloxacin are determined in human plasma using capillary electrophoresis in the presence of N-(1-naphthyl) ethylenediamine dihydrochloride as an internal standard. Ciprofloxacin is eliminated by renal and non-renal mechanisms. The drug is partially metabolized in the liver by modification of the piperazinyl group to at least four metabolites. Ciprofloxacin and its metabolites are excreted in urine by both glomerular filtration and by tubular secretion.

Ciprofloxacin: Physical Profile

Publisher Summary This chapter explores the physical profile of ciprofloxacin. The empirical formula of ciprofloxacin is C 17 H 18 FN 3 O 3 . The molecular weight, CAS number, and structural formula of ciprofloxacin are also discussed. The physical characteristics include solution pH, solubility characteristics, optical activity, X-ray powder diffraction, thermal methods of analysis and spectroscopy are discussed. Ciprofloxacin is practically insoluble in water, very slightly soluble in dehydrated alcohol and in dichloromethane, and soluble in dilute acetic acid. Since ciprofloxacin has no centers of dissymmetry, it does not exhibit optical activity. The solutions of ciprofloxacin are light sensitive and should be protected from light and freezing. The infrared absorption spectrum of ciprofloxacin is obtained in a KBr pellet using a Perkin Elmer infrared spectrophotometer and the principal peaks are noted at 3490, 3320, 2930, 2840, 1696, 1605, 1480, 1435 cm _1 . The electron impact (EI) spectrum of ciprofloxacin is recorded using a Shimadzu PQ-5000 GC-MS spectrometer and the spectrum shows a mass peak at m/z 332, and a base peak at m/z 288, resulting from the loss of the group.

Synthesis, spectral, antimicrobial, and thermal properties of Ce(III), Gd(III), Nd(III), Tb(III), and Er(III) gliclazide complexes

The complexation between the lanthanide metal ions Ce(III), Gd(III), Nd(III), Tb(III), and Er(III) and gliclazide produced 1 : 1 molar ratio metal: gliclazide (Glz) complexes coordinated in a monodentate fashion via the OH group and having the general formulas [M(Glz)Cl3(H2O)]·xH2O (M = Ce, Gd, Nd and x = 1, 3, 4, respectively) and [M(Glz)(H2O)4]Cl3·yH2O (M = Tb, Er and y = 1, 2, respectively). The structure of the synthesized lanthanide gliclazide complexes was assigned by IR, 1HNMR, and UV-Vis spectroscopy. Thermal analysis and kinetic and thermodynamic parameters gave evidence for the thermal stability of the Glz complexes. The latter showed a significant antimicrobial effect against some bacteria and fungi.