Browsing by Author "Samir, Ahmed"

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Development of simultaneous quantification method of loteprednol etabonate (LE) and its acidic metabolites, and analysis of LE metabolism in rat
(Taylor & Francis, 2019) Samir, Ahmed; Kage, Ayano; Ohura, Kayoko; Imai, Teruko
Loteprednol etabonate (LE) is a soft corticosteroid with two labile ester bonds at 17α- and 17β-positions. Its corticosteroidal activity disappears upon hydrolysis of either ester bond. Hydrolysis of both ester bonds produces the inactive metabolite, Δ1-cortienic acid (Δ1-CA). The simple high-performance liquid chromatography method using acetic acid gradient was developed for the simultaneous determination of LE and its acidic metabolites. LE was hydrolyzed in rat plasma with a half-life of 9 min. However, LE hydrolysis was undetectable in rat liver and intestine. LE hydrolysis in rat plasma was completely inhibited by paraoxon and bis(p-nitrophenyl) phosphate, thus identifying carboxylesterase as the LE hydrolase. Rat plasma carboxylesterase had a Km of 6.7 μM for LE. In contrast to the disappearance rate of LE in rat plasma, the formation rate of 17α-monoester and Δ1-CA was markedly low, and a main hydrolysate of LE was not detected in rat plasma. The metabolism of LE proceeded via different pathways in human and rat plasma. LE was slowly hydrolyzed by paraoxonase in human plasma to 17α-monoester with a half-life of 12 h, but by carboxylesterase in rat plasma to yield undetectable products, presumed to include the unstable 17β-monoester.
Green potentiometric electrode for determination of salbutamol in biological samples
(Academic Press Inc, 2022-10) Elbalkiny, Heba T; Samir, Ahmed
Clinical drug analyses and identification of pharmaceuticals in biological samples are highly crucial for thera- peutic drug monitoring, pharmacokinetic studies, and screening of illicit drugs. Various analytical tools, such as potentiometric electrodes, are used to conduct these investigations. These potentiometric electrodes are superior to other techniques in terms of greenness and cost efficacy, and thus present a good alternative for researchers. In this study, we develop an advanced electrode for the in-situ monitoring of salbutamol in plasma, this electrode was synthesized using multiwalled carbon nanotubes (MWCNT) as hydrophobic conductive substance and copper oxide nanoparticle (CuO NP) as a surface modifier, the developed electrode was compared to traditional liquid contact electrode as well as solid contact electrode and proved its superiority. The use of MWCNT improved the stability of the electrode via preventing the formation of this water layer and the CuO NP improved the sensitivity due to its high surface area and rich electronic properties. CuO NP modified electrode was used for the determination of salbutamol with a Nernstian slope of 57.4 over a linearity range of range 1.0 × 10− 7 - 1.0 × 10− 2 M, and a detection limit of 4.0 × 10− 7 M. The proposed electrode was effectively applied for the deter- mination of the cited drug in rat plasma without interference and compared with chromatographic reported method. The proposed method is economic as it has a low sample analysis cost, time saving and needs fewer manipulation steps and a simple convenient device. It also proved to be a greener method when compared with chromatographic methods using an eco-scale metric system.
A high-throughput UPLC-MS-MS Bio-analytical method for the analysis of veterinary pharmaceutical residues in Chicken Tissues, Application of efficient-valid-green (EVG) Framework as a Competence Tool
(Elsevier B.V, 2024-04) Saleh, Sarah S; Samir, Ahmed; Lotfy, Hayam M; Nessim, Christine K
Antibacterial medications are receiving the most attention due to hypersensitivity reactions and the emergence of bacterial mutants resistant to antibiotics. Treating Animals with uncontrolled amounts of antibiotics will extend beyond their lives and affect humans. This study aims to determine the concentration of the residues of sulfadimidine, sulfaquinoxaline, diaveridine, and vitamin K3 in the tissues of poultry (muscles and liver) after treatment with the combined veterinary formulation. A UPLC-MS-MS method was developed using Poroshell 120 EC[sbnd]C18 and a mobile phase composed of acetonitrile and distilled water, containing 0.1 % formic acid, in the ratio of (85:15 v/v) at a flow rate of 0.6 mL/min. Sample extraction solvent was optimized using response surface methodology (RSM) to be acetonitrile: methanol in the ratio (49.8: 50.2 v/v), and the method was validated according to the FDA bioanalytical method validation protocol over the range (50–1000 µg/Kg) for sulfaquinoxaline and (50–750 µg/Kg) for the other 3 drugs. The greenness of the sample preparation and analytical method was assessed by applying Analytical Eco-scale (AES) and AGREE coupled with AGREEprep. The Competence of the study was evaluated via the EVG framework known as Efficiency, validation, and greenness, to achieve a balance point represented by a radar chart. The method was applied to decide the time required for poultry products to be safe for human use after administration of the studied drugs. It was found that, after the administration of the last dose, minimally 7 days are required till the levels of the drugs drop to the maximum residue limit determined by the FDA/WHO in animal tissues.
Identification of esterase involved in the metabolism of two corticosteroid soft drugs
(Elsevier, 2017) Samir, Ahmed; Bodor, Nicholas; Imai, Teruko
The soft drug approach is successful in obtaining high local therapeutic efficacy without systemic adverse effects, because soft drugs are designed to be bioconverted to inactive form by hydrolytic enzymes in systemic circulation. However, there is little information about the exact nature of these metabolic enzymes. In this study, the human enzymes for biotransformation of soft drugs were investigated. Loteprednol etabonate (LE) and etiprednol dicloacetate (ED) were designed from Δ1-cortienic acid (Δ1-CA), the inactive metabolite of prednisolone, by introducing two labile ester bonds to restore the corticosteroidal activity. We found that LE and ED were mainly deactivated in human plasma rather than the liver. Inactive monoesters were produced, but the second hydrolysis to Δ1-CA was much slower. ED was hydrolyzed 10 times faster than LE in plasma (t1/2 = 1.35 ± 0.08, 12.07 ± 0.52 h respectively). Paraoxonase 1 that attached with high density lipoprotein (HDL) was found to be the major hydrolase for LE and ED in human plasma as demonstrated by enzyme inhibition and stimulation experiments and the hydrolysis in lipoproteins-rich plasma fractions. Human serum albumin (HSA) showed slight hydrolase activity against ED but not LE. LE was slowly hydrolyzed in liver (clearance: 0.21 ± 0.04 and 2.41 ± 0.13 ml/h/kg in liver and plasma, respectively) but ED wasn’t hydrolyzed at all, so LE has superior metabolism in two sites. The difficult diffusion of HDL into tissues from blood suggests the stable presence of LE at the administration site, while ED might be deactivated by its relatively rapid chemical hydrolysis and hydrolase activity of HSA, in the interstitial fluid of the administration tissue. Moreover, deactivation in plasma and strong protein binding (around 98%) minimize the adverse effects of LE and ED in the systemic circulation.
Identification of Major Esterase Involved in Hydrolysis of Soft Anticholinergic (2R3’R-SGM) Designed From Glycopyrrolate in Human and Rat Tissues
(Elsevier, 2019) Samir, Ahmed; Ohura, Kayoko; Bodor, Nicholas; Imai, Teruko
The glycopyrrolate soft analog, SGM, designed to be easily hydrolyzed into the significantly less active zwitterionic metabolite, SGa, typifies soft drug that reduces systemic side effects (a problem often seen with traditional anticholinergics) following local administration. In this study, hydrolysis of 2R3’R-SGM, the highest pharmacologically active stereoisomer of SGM, was investigated in human and rat tissues. In both species, 2R3’R-SGM was metabolized to 2R3’R-SGa in plasma but was stable in liver and intestine. The half-life of 2R3’R-SGM was found to be 16.9 min and 9.8 min in human and rat plasma, respectively. The enzyme inhibition and stimulation experiments showed that plasma paraoxonase 1 (PON1) is responsible for the hydrolysis of 2R3’R-SGM in humans and rats. The PON1-mediated hydrolysis of 2R3’R-SGM was confirmed in the lipoprotein-rich fractions of human plasma. As PON1 is naturally attached to high-density lipoprotein, it might be absent in topical tissues where 2R3’R-SGM is applied, supporting its local stability and efficacy. The metabolic behavior of 2R3’R-SGM indicates that it is an ideal soft drug to be detoxified as soon as it moves into systemic circulation. Furthermore, the similarity of 2R3’R-SGM metabolism in humans and rats showed that the rat is a suitable animal for preclinical study.
Increment of Lysosomal Biogenesis by Combined Extracts of Gum Arabic, Parsley, and Corn Silk: A Reparative Mechanism in Mice Renal Cells
(Hindawi, 07/11/2020) Helmy, Aya; El-Shazly, Mohamed; Omar, Nesreen; Rabeh, Mohamed; Abdelmohsen, Usama Ramadan; Tash, Reham; Salem, Mohammad Alaraby; Samir, Ahmed; Elshamy, Ali; Singab, Abdel Nasser B.
Gum Arabic (GA), parsley, and corn silk have been traditionally used for renal failure patients worldwide. This study aimed at probing the mechanism of the combined extracts, namely, GA (3 g/kg/day), parsley (1 g/kg/day), and corn silk (200 mg/kg/day), as nephroprotective agents in mice after amikacin (1.2 g/kg) single dose through exploration of their action on G-protein coupled receptors (GPR) 41 and 43 and the ensuing lysosomal biogenesis. Western blotting was employed for renal levels of bcl-2-associated X protein (BAX) and cytosolic cathepsin D; cell death markers, nuclear transcription factor EB (TFEB), and lysosomal associated membrane protein-1 (LAMP-1); and lysosomal biogenesis indicators. Liquid chromatography–mass spectrometry (LC-MS) and docking were also employed. After amikacin treatment, BAX and cathepsin D levels were upregulated while LAMP-1 and nuclear TFEB levels were inhibited. The combined extracts inhibited BAX and cytosolic cathepsin D but upregulated LAMP-1 and nuclear TFEB levels. Docking confirmed GPR modulatory signaling. The combined extracts showed GPR signal modulatory properties that triggered lysosome synthesis and contributed to reversing the adverse effects of amikacin on renal tissues.
New developed spectrophotometric method for simultaneous determination of salmeterol xinafoate and fluticasone propionate in bulk powder and Seritide® diskus inhalation
(Elsevier, 2012) Samir, Ahmed; Salem, Hesham; Abdelkawy, Mohammad
A new simple, accurate, precise, rapid and economical method was developed for the simultaneous determination of Salmeterol xinafoate and Fluticasone propionate in their binary mixture in bulk powder and Seritide diskus® inhalation. The new method depends on new calculations using the mixture’s absorbance at 225 and 256.5 nm where the absorptivity of Salmeterol xinafoate is double the absorptivity of Fluticasone propionate, while the content of Salmeterol xinafoate was determined by measuring the absolute value of the first derivative ultraviolet curves at 352 nm, without interference from Fluticasone propionate. The proposed method was validated and the results obtained by adopting the proposed method were statistically analyzed and compared with those obtained by reported methods.
Optimization of two charge transfer reactions for colorimetric determination of two beta 2 agonist drugs, salmeterol xinafoate and salbutamol, in pharmaceutical and biological samples
(Elsevier, 13/09/2021) Samir, Ahmed; Salem, Hesham; Abdelkawy, Mohammed
Beta 2 agonists are well known for their use in the treatment of asthma and COPD however in the last few years new indications of beta 2 agonist appeared like reduction of local fats and treatment of preterm labour which required the formulation of new dosage forms and administration strategies. The new developments require accurate, economic and feasible methods the determination of these drugs to facilitate testing the newly introduced dosage forms and to study the pharmacokinetics and pharmacodynamics regarding the modern uses. In this study two rapid, sensitive and economic colorimetric methods for the determination of salmeterol xinafoate and salbutamol in pharmaceutical dosage forms and spiked plasma were developed and validated. The developed methods depends on the optimized reaction of the studied drugs with two charge transfer reagents, 2,3-dochloro-5,6-dicyano-1,4-benzoquonone (DDQ) and chloranilic acid (CA) to produce coloured complexes measured at 460 and 529nm for DDQ and CA respectively. The developed methods showed high accuracy of 99.52±1.108, 101.03±0.389, 100.04±1.520 and 100.3±0.951 for salmetrol xinafoate and salbutamol with DDQ and CA respectively. The proposed methods were successfully used for the determination of the studied drugs in their dosage forms and spiked plasma with high accuracy and precision and the results were compared to reported methods.
Simultaneous Determination of Salmeterol Xinafoate and Fluticasone Propionate in Bulk Powder and Seritide Diskus using High Performance Liquid Chromatographic and Spectrophotometric Method
(Pharmaceutica Analytica Acta, 2012) Samir, Ahmed; Salem, Hesham; Abdelkawy, Mohammad
Five methods were developed for simultaneous determination of Salmeterol xinafoate (SAM) and Fluticasone propionate (FLU) without previous separation. In the first method (HPLC), a reversed-phase column and a mobile phase of acetonitrile: methanol (80:20 v/v) at 0.5 mLmin-1 flow rate was used to separate both drugs and UV detection at 220 nm. Linearity was obtained in concentration ranges of 50-500 µgmL-1 for Salmeterol xinafoate Fluticasone propionate. In the second method both drugs were determined using first derivative UV spectrophotometry, with zero crossing measurement at 352 and 269.5 nm for Salmeterol xinafoate and Fluticasone propionate, respectively. The third method depends on first derivative of the ratios spectra by measurements of the amplitudes at 334 and 337.5 nm for Salmeterol xinafoate and at 225 and 231.5 nm for Fluticasone propionate. Calibration graphs were established in the range of 4-28 µgmL-1 for both Salmeterol xinafoate and Fluticasone propionate. The fourth one depend on isosbestic point at 237.5 nm, while the content of Salmeterol xinafoate was determined by measuring the absolute value of the ultraviolet curves at 343 nm, without interference from Fluticasone propionate. All the proposed methods were extensively validated. They have the advantage of being economic and time saving. All the described methods can be readily utilized for the analysis of pharmaceutical formulations. The results obtained by adopting the proposed methods were statistically analyzed and compared with those obtained by official methods.