Samia Mostafa

Spectrophotometric determination of ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation

A spectrophotometric method was described for the determination of the antibacterial quinolone derivatives, ciprofloxacin, enrofloxacin and pefloxacin through charge transfer complex formation with three different acceptors. Chloranilic acid (CL) was utilized for their determination, forming charge transfer complex with lambdamax 520 nm. The proposed method was applied for determination of Ciprocin tablets, Enroxil oral solution, Peflacin ampoules and Peflacin tablets, with mean percentage accuracies, 99.58+/-1.25,99.94+/-0.96,100.91+/-1.59 and 99.86+/-1.003. Also, tetracyanoethylene (TCNE) was utilized in the determination of the concerned compounds forming charge transfer complexes with maximum absorbances at lambdamax 335 nm for ciprofloxacin and at lambdamax 290 nm for both enrofloxacin and pefloxacin. The procedure was applied for determination of Ciprocin tablets, Enroxil 10% oral solution, Peflacine tablets and Peflacine ampoules with mean percentage accuracies 99.40+/-1.27,99.95+/-0.90,98.98+/-1.565 and 99.88+/-0.998, respectively. Also, 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) was utilized for determination of pefloxacin forming charge transfer complex with maximum absorbance at lambdamax 460 nm. The procedure was applied for determination of peflacine tablets and peflacine ampoules with mean percentage accuracies 100.40+/-0.76 and 99.91+/-0.623, respectively. Statistical analysis of the obtained results showed no significant difference between the proposed method and other official and reported methods as evident from the t-test and variance ratio.

Spectrophotometric determination of enrofloxacin and pefloxacin through ion-pair complex formation.

Two simple, quick and sensitive spectrophotometric methods are described for the determination of enrofloxacin and Pefloxacin. The methods are based on the reaction of these drugs with bromophenol blue (BPB) and methyl orange (MO) in buffered aqueous solution at pH 2.3-2.5 in case of bromophenol blue and at pH 3.6 with MO to give highly coloured complex species, extractable with chloroform. The coloured products are quantitated spectrophotometrically at 420 and 424 nm for BPB and MO, respectively. Optimisation of the different experimental conditions is described. Beers law is obeyed in the concentration ranges 2-12 and 2-18 microg ml(-1) with BPB and in the ranges 1-12 and 4-40 microg ml(-1)with MO for enrofloxacin and pefloxacin, respectively. The proposed methods are applied for determination of Enroxil oral solution, Peflacine tablets and Peflacine ampoules with mean percentage accuracies 99.5+/-0.99, 99.39+/-1.05 and 100.02+/-0.895, respectively, with BPB and 100.30+/-0.89, 100.25+/-0.98 and 100.20+/-0.72, respectively, with MO.

Design, synthesis, and biological evaluation of novel thiazolidinediones as PPARγ/FFAR1 dual agonists.

Diabetes mellitus is a chronic metabolic disorder that affects more than 180 million people worldwide. Peroxisome proliferator activated receptors (PPARs) are a group of nuclear receptors that have been targeted by the thiazolidinedione (TZD) class of compounds for the management of type II diabetes. PPARγ is known to regulate adipogenesis and glucose metabolism. Another emerging target for the design of antidiabetic agents is the free fatty acid receptor 1 (FFAR1), previously known as GPR40. Agonists of this receptor were found to enhance insulin secretion in diabetic patients. It has been reported that some thiazolidinediones (TZDs) activate FFAR1 with micromolar potency. In this study, based on docking studies into the crystal structure of PPARγ and a homology model of FFAR1, nineteen compounds were designed, synthesized, and biologically tested for agonistic activity on both receptors. Nine compounds showed promising dual activity, with two compounds, 11a and 5b, having affinities in the low micromolar range on both targets. These molecules represent the first antidiabetic agents that could act as insulin sensitizers as well as insulin secretagogues.

HPLC and Chemometric Methods for the Simultaneous Determination of Miconazole Nitrate and Nystatin

High-performance liquid chromatography (HPLC) and chemometric methods were applied to the simultaneous determination of the two nonsteroidal antifungal drugs, miconazole (MIC) and nystatin (NYS). The applied chemometric techniques are multivariate methods including classical least squares, principal component regression and partial least squares methods. The ultraviolet (UV) absorption spectra of the standard solutions of the training and validation sets in methanol are recorded in the range of 280-320 nm at 0.2-nm intervals. The HPLC method depends on reversed-phase separation using a C18 column. The mobile phase consists of a mixture of methanol-acetonitrile-ammonium acetate buffer (pH 6; 50 mM) (60:30:10 v/v/v). The UV detector was set at 230 nm. The developed methods were validated and successfully applied to the simultaneous determination of MIC and NYS in their tablets. The assay results obtained using the chemometric methods were statistically compared to those of the HPLC method and good agreement was observed.

RP-HPLC/Pre-Column Derivatization for Analysis of Omeprazole, Tinidazole, Doxycycline and Clarithromycin

A validated, reliable and accurate reversed-phase high performance liquid chromatographic method using pre-column derivatization was adopted for the simultaneous determination of two ternary mixtures containing omeprazole, tinidazole and doxycycline hyclate or clarithromycin. Separation was achieved on a C18 column, through a gradient elution system using acetonitrile-methanol-water adjusted to pH = 6.60. Drugs were detected at 277 nm over concentration ranges of 1-112, 5-125, 2.5-550 and 2.5-100 µg/mL for omeprazole, tinidazole, doxycycline hyclate and clarithromycin, respectively. This is the first method that has isolated and identified clarithromycin derivative by infrared and mass spectroscopy. This method is the first study for the simultaneous determination of omeprazole, tinidazole, doxycycline hyclate and clarithromycin in combined mixtures and pharmaceutical formulations.

Development and validation of a sensitive UHPLC-MS/MS method for the simultaneous analysis of tramadol, dextromethorphan chlorpheniramine and their major metabolites in human plasma in forensic context: application to pharmacokinetics

The prerequisites for forensic confirmatory analysis by LC/MS/MS with respect to European Union guidelines are chromatographic separation, a minimum number of two MS/MS transitions to obtain the required identification points and predefined thresholds for the variability of the relative intensities of the MS/MS transitions (MRM transitions) in samples and reference standards. In the present study, a fast, sensitive and robust method to quantify tramadol, chlorpheniramine, dextromethorphan and their major metabolites, O-desmethyltramadol, dsmethyl-chlorpheniramine and dextrophan, respectively, in human plasma using ibuprofen as internal standard (IS) is described. The analytes and the IS were extracted from plasma by a liquid-liquid extraction method using ethyl acetate-diethyl-ether (1:1). Extracted samples were analyzed by ultra-high-performance liquid chromatography coupled to electrospray ionization tandem mass spectrometry (UHPLC-ESI-MS/MS). Chromatographic separation was performed by pumping the mobile phase containing acetonitrile, water and formic acid (89.2:11.7:0.1) for 2.0 min at a flow rate of 0.25 μL/min into a Hypersil-Gold C18 column, 20 × 2.0 mm (1.9 µm) from Thermoscientific, New York, USA. The calibration curve was linear for the six analytes. The intraday precision (RSD) and accuracy (RE) of the method were 3-9.8 and -1.7-4.5%, respectively. The analytical procedure herein described was used to assess the pharmacokinetics of the analytes in 24 healthy volunteers after a single oral dose containing 50 mg of tramadol hydrochloride, 3 mg chlorpheniramine maleate and 15 mg of dextromethorphan hydrobromide.

Synthesis and biological evaluation of some N-arylpyrazoles and pyrazolo[3,4-d]pyridazines as anti-inflammatory agents.

A series of 3,4‐bis‐chalcone‐N‐arylpyrazoles 3a–k was prepared from diacetyl pyrazoles 2a–e. The reaction of 2d and 2e with hydrazine hydrate gave pyrazolo[3,4‐d]pyridazine derivatives 4a–b. Furthermore, the reaction of 2a–e with thiosemicarbazide afforded pyrazolo[3,4‐d]pyridazine thiocyanate salts 5a–e. The synthesized compounds were subjected to in vivo anti‐inflammatory and ulcerogenic activity measurements, in addition to determination of their in vitro COX selectivity, to give a full profile about their anti‐inflammatory activities. Compounds 3c, 3f, 3i, and 3e showed significant anti‐inflammatory activity among the synthesized compounds. Moreover, docking studies were performed to give an explanation for their anti‐inflammatory activity through COX selectivity.

STABILITY-INDICATING CHROMATOGRAPHIC METHOD FOR THE DETERMINATION OF BENZONATATE, DIPHENHYDRAMINE, GUAIFENESIN, AND PHENYLEPHRINE

A high-performance liquid chromatographic method has been developed for the simultaneous analysis of benzonatate (BNZ), diphenhydramine hydrochloride (DPH), guaifenesin (GFN), and phenylephrine hydrochloride (PEP). The separation was achieved using a Thermo C18 reversed-phase column (250 mm × 4.6 mm ID, particle size 5 µ). Dual mode gradient elution was used for the separation and UV detection was carried out at 222 nm. The method was specific and stability indicating as chromatographic conditions provided adequate separation of degradation products. The method showed good linearity in the range of 5–400, 1–120, 3–300, and 2–100 µg/mL for BNZ, DPH, GFN, and PEP, respectively. All the square of the correlation coefficients are 0.999. The degradation products were isolated and identified by NMR, IR, and mass spectroscopy. The proposed method proved to be accurate, precise, selective, and robust. The applicability of the method was evaluated in commercial dosage form analysis as well as in stability studies.

Quantitative determination of captopril, perindopril erbumine, moexipril hydrochloride, and ramipril in bulk and pharmaceutical preparations by high performance liquid chromatography

A high-performance liquid chromatographic method was developed for simultaneous determination of four ACE-inhibitors: captopril (CAP), perindopril erbumine (PER), moexipril hydrochloride (MOEX), and ramipril (RAM) in pharmaceutical formulations. The chromatographic separation was performed on Shim-pack cyanopropyl column with a mobile phase consisting of methanol-10mM ammonium acetate buffer (pH 6.0) in a ratio of (40: 60, v/v) at flow rate 1 ml min. the analysis was performed at ambient temperature using UV detector setting at 210 nm. All ACE-inhibitors were separated within seven min. The calibration curves were linear (r ≥ 0.9994) over a concentration range from 5 to 50 μg ml. the method was successfully applied to commercially available pharmaceutical preparations. The validity of the method was examined comparing the results obtained with official or published methods.

Synthesis, biological evaluation, and molecular docking investigation of benzhydrol- and indole-based dual PPAR-γ/FFAR1 agonists

Type-2 diabetes mellitus is a progressive cluster of metabolic disorders, representing a global public health burden affecting more than 366 million people worldwide. We recently reported the discovery of three series of novel agents showing balanced activity on two metabolic receptors, peroxisome proliferator activated receptor-γ (PPAR-γ) and free fatty acid receptor 1 (FFAR1), also known as GPCR40. Our designing strategy relied on linking the thiazolidinedione head with known GPCR privilege structures. To further investigate this concept, two new scaffolds, the benzhydrol- and indole-based chemotypes, were introduced here in. Our optimization campaign resulted in three compounds; 15a, 15c, and 15d, with affinities in the low micromolar range on both targets. In vivo study of selected test compounds, revealed that 15c possesses a significant anti-hyperglycemic and anti-hyperlipidemic activities superior to rosiglitazone in fat-fed animal models. Molecular docking analysis was conducted to explain the binding modes of both series. These compounds could lead to the development of the unique antidiabetic agent acting as insulin sensitizer as well as insulin secretagogue.