Browsing by Author "Mowaka, Shereen"

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Chlorambucil-adducts in DNA analyzed at the oligonucleotide level using HPLC-ESI MS.
(American Chemical Society, 2009) Mohamed, Dalia; Mowaka, Shereen; Jürgen, Thomale; Michael, W Linscheid
Chlorambucil (N,N-bis(2-chloroethyl)-p-aminophenylbutyric acid) is a bifunctional alkylating drug belonging to the nitrogen mustard group and is widely used as an anticancer agent. As the antitumor activity of the nitrogen mustards is based on the formation of adducts with genomic DNA, calf thymus DNA-Chlorambucil adducts were the major target in this study. Calf thymus DNA was incubated with Chlorambucil to induce the formation of a wide variety of adducts. Subsequently, enzymatic digestion of the DNA was performed using Benzonase and Nuclease S1 aiming at the production of oligonucleotides. Separation and structure elucidation of the individual DNA-Chlorambucil adducts was achieved using HPLC interfaced to electrospray ionization ion trap mass spectrometry. Both trinucleotide and tetranucleotide Chlorambucil adducts were detected. The majority of the detected trinucleotide adducts involved monofunctional alkylation with guanine being the hotspot for alkylation. Only a few bifunctional trinucleotide adducts both intra- and interstrand cross-links were found. On the contrary, cross-linked adducts were the major detected tetranucleotides in which the intrastrand cross-links predominated over the interstrand cross-links. To a lesser extent, monofunctional guanine alkylated tetranucleotides were detected as well. With MS(n) experiments, the detailed structures of Chlorambucil adducts of the tri- and tetranucleotides were determined.
Kinetic spectrophotometric determination of flavonoids using alka-line potassium permanganate
(Analytical Chemistry An Indian Journal, 2013) Mowaka, Shereen; Mohamed, Dalia
Two simple and sensitive kinetic methods were developed for the determination of diosmin and hesperidin in bulk and pharmaceutical preparations. The proposed methods are based on kinetic investigation of the oxidation reaction of the drugs with alkaline potassium permanganate at room temperature for a fixed time of 20 min and 15 min for the first and second methods, respectively. In the first method the absorbance of the green colored manganate ion produced by diosmin and hesperidin was measured at 610 nm. Alternatively in the second method, the decrease in the absorbance of permanganate ion after addition of diosmin was measured at 525 nm. Calibration graphs were linear over the concentration range 5.0- 25.0 and 1.0-20.0 ìg/mL for diosmin using the two methods, respectively and 1.10-2.77 ìg/mL for hesperidin, using the first method. The results obtained were compared statistically with those obtained by a reported method and showed no significant differences regarding accuracy and precision. In addition, the activation parameters such as Ea, ï H, ï S and ï G were also evaluated for the reaction and found to be 15.85 KJ mol-1, 40.79 KJmol-1, 25.59 JK-1mol-1 and -7.63 KJmol-1, respectively.
Simultaneous quantitative analysis of tamsulosin and finasteride in pharmaceutical dosage form by U-HPLC Tandem mass spectrometry
(European Journal of Chemistry, 2014) Mohamed, Dalia; Mowaka, Shereen; Mostafa, Ahmed
A sensitive, rapid, selective and accurate liquid chromatography coupled to quadrupole tandem mass spectrometry (LC-MS/MS) method was developed for simultaneous identification and quantification of tamsulosin and finasteride in bulk and in their combined dosage form. Chromatography was performed on a Hypersil gold 50 mm × 2 mm (1.9 μm) column, using acetonitrile:ammonium acetate (90:10, v:v) pH = 3.5 as the mobile phase. Protonated ions formed by a turbo ion-spray in positive mode were used to detect the analytes as well as the internal standard (IS). MS/MS detection was carried out by monitoring the fragmentation of 408.74 → 227.29 (m/z), 373.11 → 304.96 (m/z) and 255.75 → 166.15 (m/z) for tamsulosin, finasteride and diphenhydramine (IS), respectively, on a triple quadrupole mass spectrometer. The linearity was obtained over the concentration range of 1.6-40.0 ng/mL for tamsulosin and 20.0-500.0 ng/mL for finasteride with a lower limit of detection of 0.5 ng/mL and 5.0 ng/mL for the two drugs, respectively. The proposed method was successfully applied to tamsulosin and finasteride determination in pharmaceutical dosage form. The results obtained were statistically analyzed and compared with those of reference ones; in addition, the method was validated according to USP 34 recommendations. The simplicity and sensitivity of this method allows its use in the quality control of the cited drugs and can be extended for routine analysis of the drugs in their pharmaceutical preparations.
Square Wave Voltammetric Determination of Ropinirole HCl in Bulk, Dosage Forms and Biological Samples on Carbon Paste Electrode
(Journal of Pharmaceutical Research International, 2016) HI Habib, Ibrahim; Rizk, Mohamed; Mohamed, Dalia; Mowaka, Shereen; Th El-Eryan, Rasha
Aim: Voltammetric determination for of Ropinirole HCl. Study: We will study the behaviour of Ropinirole HCl on the carbon paste electrode. So several factors such as pH, type of pasting oil, pulse amplitude and scan rate were studied to optimize the condition for voltammetric determination of drug. Place and Duration of Study: Microanalytical Chemistry Laboratory, Applied Organic Chemistry Department, National Research Centre, Dokki, Giza, Egypt, between August 2015 and December 2015. Methodology: Square wave voltammetry (SWV) was employed in order to determine Ropinirole in bulk powder and plasma in a voltammetric cell containing 10 mL of 0.1 mole L-1 sulphuric acid as supporting electrolyte. After every aliquot addition, the solution was stirred for 30 s at 2000 rpm, rested for 10 s then SWV mode was ramped from +300 to +1600 mV with scan rate 100 mV s-1 and pulse amplitude 50 mV. The experiment was triplicated for every standard solution addition. Results: A good linearity was obtained over a range of (4.96x10-6 to 3.90x10-5 mol L-1) with mean recovery and relative standard deviation (RSD) values of 99.15% and 3.7%, respectively. The lower detection (LOD) and quantification (LOQ) limits were found to be (1.48x10-6 and 4.96x10-6 mol L-1) respectively at Square wave (SWV) mode. The accuracy and precision of the method were presented with inter and intra days determinations which were within acceptable limits. The method was applied successfully for determining the active ingredients in pharmaceutical preparations with mean percentage recoveries ± RSD of 98.38±3.1 and in spiked human plasma with the mean of recoveries ± RSD, 99.56±3.63%. Conclusion: An economic, accurate and precise electrochemical method has been developed and validated for the determination of Ropinirole HCl in bulk, dosage form and human plasma.
Structures of oxaliplatin-oligonucleotide adducts from DNA.
(John Wiley & Sons, Ltd., 2012) Mohamed, Dalia; Mowaka, Shereen; Hochkirch, Ulrike; Jürgen, Thomale; W Linscheid, Michael
Oxaliplatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA-protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin-DNA intrastrand and interstrand adducts at the oligomer level using high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) and HPLC/inductively coupled plasma-MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI-ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level. Copyright © 2012 John Wiley & Sons, Ltd.