Tawfiq Arafat - Academia.edu (original) (raw)

Papers by Tawfiq Arafat

The aim of the study was to evaluate the bioequivalence between a newly developed generic tablet ... more The aim of the study was to evaluate the bioequivalence between a newly developed generic tablet containing fixed-dose combination of amlodipine besylate, valsartan and hydrochlorothiazide (10/160/25 mg), and the reference brand product Exforge HCT ® Methods: The brand (reference) and the test (generic) products were administered to thirty-nine healthy subjects. A fasting, laboratory blind, single-dose, two-treatment, two-period, two-sequence, randomized crossover design was conducted with 14 d washout period between dosing. Serial blood samples were withdrawn from each subject immediately before dosing (zero time), and then at 0.33

Glimepiride and sildenafil citrate are metabolized in liver by cytochrome p450, and there is a po... more Glimepiride and sildenafil citrate are metabolized in liver by cytochrome p450, and there is a possibility of drug interactions if they are taken together. Therefore, a simple and sensitive method for simultaneous determination and validation of sildenafil with glimepiride in rat plasma has been developed by using high performance liquid chromatography-mass spectrometry (HPLC-MS). A mixture of 70% methanol, 30% of 0.1% formic acid in water was used as a mobile phase, ACE 5 C18 column, the flow rate of 0.5 mL/min was used, the autosampler injection volume was 5 μL, and clarithromycin was used as an internal standard. The accuracy for glimepiride and sildenafil in all the three days of validation and all the four tested target concentration was 99.7% and 98.9% respectively. The standard curves for both drugs matched the requirements, linear relation (R2) ranged between; (0.994 to 1). The serum level of both drugs was lowered when combined together, in comparison Serum sildenafil level was affected by the combination to a greater extent than glimepiride. Sildenafil was found to decrease significantly when it is used in a combination (34.5 ng/mL) compared to solitary drug use (57.8 ng/mL).

Journal of Clinical Laboratory Analysis, 2001

Amlodipine is a calcium channel antagonist of the dihydropyridine group. It is effective for trea... more Amlodipine is a calcium channel antagonist of the dihydropyridine group. It is effective for treating hypertension, chronic stable angina, and vasospastic angina. However, it is difficult clinically to pinpoint the maximum dosage for antihypertensive activity of the drug without having parallel data on the plasma drug concentrations. The methods for assaying amlodipine are either gas chromatography with electron capture detector or liquid chromatography coupled with tandem mass spectrometry (or with an electrochemical detector), which needs tedious derivatization, and is expensive and time consuming. Therefore, in this study we developed an enzyme immunoassay for determining amlodipine in plasma. Anti-amlodipine antibodies were produced following immunization of bovine serum albumin-amlodipine conjugate. These specific antibodies were used in a competitive biotin-avidin-based enzyme-linked immunosorbent assay to measure amlodipine in plasma. Biotin was linked to the antibodies in order to enhance the sensitivity of the assay. The assay was specific for the free form of amlodipine with a detection limit of 0.1 ng/ml and the intraand interassay coefficient of variation ranged from 1.6-10.2%. This immunoassay provides a sensitive, reliable, rapid, and accurate method for determination of amlodipine in plasma, which can be used in therapeutic drug monitoring pharmacokinetic studies and pharmaceutical analysis.

Tetrahedron, Nov 1, 2006

A peptide-like self-immolative molecular clip is required for release of active drugs from prodru... more A peptide-like self-immolative molecular clip is required for release of active drugs from prodrugs by endopeptidases. Upon cleavage from the carrier, this clip must collapse and release the drug rapidly. A series of aminoacyl-5,5-dimethylthiaproline (Aaa-Dmt) N-(2-(4-nitrophenyl)ethyl)amides were designed. Boc-l-aminoacyl fluorides were coupled with R-DmtOH to give Boc-l-Aaa-R-DmtOH, which were converted to the Boc-l-Aaa-R-Dmt N-(2-(4-nitrophenyl)ethyl)amides. The l,S diastereomeric series was prepared by the reaction of Boc-Aaa PFP esters with S-DmtOH. The l-Aaa-Dmt N-(2-(4-nitrophenyl)ethyl)amides were allowed to cyclise to diketopiperazines (DKPs) in aqueous buffers, expelling 2-(4-nitrophenyl)ethylamine as a model for amine-containing drugs. Reaction rates were dependant on pH. In the l,R diastereomeric series, increasing steric bulk of the Aaa side-chain (Gly, Ala, Phe, Val) led to decrease in the reaction rate. However, in the l,S series, the greatest rate of reaction was observed for the most bulky amino-acid (Val), with t½=15min at pH 8.0. The effects of steric bulk and stereochemistry are rationalised through conformational analysis (NMR and X-ray crystallography) of the starting dipeptide amides, the product diketopiperazines and key analogues. Since the dipeptides are (almost) exclusively in the cis-amide conformation, trans–cis interconversion is not relevant. The data suggest that steric interactions in the reacting conformations of the dipeptide amides, as they form the tetrahedral intermediates, are the controlling factors. Thus, l-Aaa-S-Dmt amides are shown to be excellent candidates for incorporation into the design of novel prodrugs.

International Journal of Molecular Sciences, Sep 29, 2022

This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY

Journal of Chromatography A, 2020

Jordan Journal of Pharmaceutical Sciences, Jul 15, 2010

A simple, sensitive and precise HPLC method for the quantitation of alfuzosin in human plasma has... more A simple, sensitive and precise HPLC method for the quantitation of alfuzosin in human plasma has been developed and validated. Commercially available atenolol was used as an internal standard. After liquid-liquid extraction, alfuzosin and atenolol (IS) in human plasma were ...

Journal of analytical & pharmaceutical research, Dec 9, 2016

Background: Dried blood spot (DBS) have been applied in many application as alternate analytical ... more Background: Dried blood spot (DBS) have been applied in many application as alternate analytical solution for limitations and challenges in conventional methods, and validated methods demand by DBS technique are still required in nicotine (Nic) research area. Aim: The development and validation of a new bioanalytical method for simultaneous determination of Nic and cotinine (Cot) in human blood using DBS and LC-Orbitrap MS technique. Methods: The DBS was punched at 6.35 mm diameter and extracted by 10% w/v of trichloroacetic acid solution, containing Nic-d3 as an internal standard (IS). The extracted samples were then injected into a Kinetex-C18 column and eluted by mobile phase of methanol:water:formic acid (10:90:0.001, v/v/v). Chromatographic effect for DBS was investigated by decentralized disk punching (peripheral area). The developed method was validated according to European and American guidelines for bioanalytical method validation. Results: Nic, Cot and IS were detected accurately by Orbitrap-MS using heated-ESI source at positive ions m/z of 163.1235, 177.1028 and 166.1423, respectively. The established calibration ranges for Nic and Cot were linear between 5-250 ng/mL and 10-500 ng/mL, respectively. Within-and between-run measurements accuracy for Nic and Cot were all higher than 80 % for LLOQ and 85 % for QC levels, and the measurements precision for Nic and Cot were all within 15 %. Conclusion: The developed method for Nic and Cot determination in human blood was successfully validated using DBS LC-Orbitrap MS technique. Nic and Cot investigation was not affected by DBS's chromatographic influence.

BMC complementary medicine and therapies, Apr 25, 2023

Background Apitherapy is an emerging field in cancer research, particularly in developing communi... more Background Apitherapy is an emerging field in cancer research, particularly in developing communities. The potency of Melittin (MEL), a major constituent in bee venom is accounted for the cytotoxic capacity against cancer cells. It is postulated that the genotype of bees and the time of venom collection influences its specific activity against certain types of cancer. Method Hereby, Jordanian crude bee venom (JCBV) was collected during different seasons of the year, specifically spring, summer and autumn and investigated for in vitro antitumour effects. Venom collected during springtime comprised the highest quantity of MEL in comparison to venom collected some other time. Springtime-collected JCBV extract and MEL were tested on an immortal myelogenous leukaemia cell line, namely K562 leukemic cells. Treated cells were examined for cell modality via flow cytometry analysis and cell death mediating gene expressions. Results Springtime-collected JCBV extract and MEL showed an IC 50 of 3.7 ± 0.37 μg/ml and 1.84 ± 0.75 μg/ml, respectively. In comparison to JCBV and positive control, MEL-treated cells exhibited late apoptotic death with a moderate cellular arrest at G0/G1 and an increase of cell number at G2/M phase. Expression of NF-κB/MAPK14 axis was inhibited in MEL and JCBV-treated cells, as well as expression of c-MYC and CDK4. Moreover, marked upregulation in ABL1, JUN and TNF was observed. In conclusion, springtime-collected JCBV showed the highest content of MEL while both JCBV and pure MEL showed apoptotic, necrotic, and cell cycle arrest efficiency against K562 leukemic cells. Conclusion Integration of bee venom in chemotherapy needs more investigation and should be carefully translated into clinical use. During such translation, the correlation of bee genotype, collection time and concentration of MEL in CBV should be profiled.

Journal of Pharmacy and Bioallied Sciences, 2019

Context: Diet and beverages are thought to have notable effects on drugs. Recently, this relation... more Context: Diet and beverages are thought to have notable effects on drugs. Recently, this relationship has received significant consideration. Aims: To develop and validate a simple, rapid, and sensitive method for the determination of glimepiride in rat serum. This will be performed using high-performance liquid chromatography–mass spectrometry (HPLC-MS/MS). Potential pharmacokinetic interactions between glimepiride and the soft drink, Vimto, will also be investigated in the serum of experimental rats. Materials and Methods: HPLC-MS/MS was constructed and clarithromycin was used as an internal standard. Results: The method was validated in terms of linearity, precision, accuracy, stability, and system suitability parameters. The method was found to be satisfactory and suitable for the determination of glimepiride. The precision of glimepiride was high (coefficient of variation, CV% <15%), the accuracy over all 3 days of validation was within the accepted criteria. Glimepiride peak serum concentration (Cmax) was 126.01ng/mL and was reached within 1h (Tmax) of administration. Mean area under curve (AUC) was 964.70ng/mL and was reached within 24h of administration. The Vimto soft drink significantly (P < 0.050) reduced glimepiride peak serum concentration to 57.87ng/mL and was reached within 2h of administration. AUC was significantly reduced to 335.04 ngFNx01h/mL (P < 0.050). Conclusion: Glimepiride pharmacokinetic parameters such as Cmax and AUC were significantly affected by the Vimto soft drink. Therefore, this study developed a simple, rapid, and sensitive method for validation and determination of the effects of soft drinks on drugs using the LC-MS/MS method.

Drug Development and Industrial Pharmacy, 1988

... It was shown Page 16. 2142 ARAFAT, SALEH, AND BADWAN that polymorphic transition took place f... more ... It was shown Page 16. 2142 ARAFAT, SALEH, AND BADWAN that polymorphic transition took place from the metastable topthe ... Miss. Lina Nabulsi and Mr. M. Ashraf of the Jordanian Pharma-ceutical Manufacturing Co., is highly appreciated. REFERENCES ...

BMC Complementary Medicine and Therapies

International Journal of Food Properties

Current Research in Nutrition and Food Science Journal, 2020

Introduction: Bread is the staple food in Jordan and there are plenty of bread types advertised t... more Introduction: Bread is the staple food in Jordan and there are plenty of bread types advertised there as healthy and multi-grain breads. These breads have diverse health and nutritional effects. This research aimed at studying the glycemic and insulinemic responses of 6 types of multi-grain breads marketed in Jordan, in addition to the local white bread, and verifying the nutrient and health claims of these breads. Methods: The glycemic and insulinemic responses were obtained in 10 participants (5 males and 5 females) according to the standard method. Six types of test breads (TB1 – TB6) were tested against white bread (WB) as a reference. Results: Among all the 6 tested breads and the local white bread, the lowest GI bread (TB6) has the lowest energy density and percentages of carbohydrate and fat, while having the highest percentages of protein, ash, fiber, and moisture. On the other hand, the highest GI bread (TB5) has only the lowest moisture percentage and the highest carbohydr...

Tropical Journal of Pharmaceutical Research, 2015

To assess the influence of smoking cigarettes on the pharmacokinetics of the antiplatelet drug, c... more To assess the influence of smoking cigarettes on the pharmacokinetics of the antiplatelet drug, clopidogrel. Methods: Thirty four male patients, mean age and weight of 59.3 years and 81.1 kg, respectively, who underwent percutaneous coronary intervention (PCI), took part in the study. Each subject received an oral loading dose of 600 mg clopidogrel eight tablets, each 75 mg). Clopidogrel carboxylate plasma level was measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to achieve peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0-∞). Other parameters measured include gamma-glutamyltransferase enzyme (GGT), low density lipoprotein cholesterol (LDL-cholesterol), blood urea nitrogen (BUN) and platelet count. Results: Nineteen patients were smokers (55.9 %). Smokers had higher levels of GGT compared to

Journal of Heterocyclic Chemistry, 2007

Some ester, amide and thioether derivatives of lupinine, aminolupinine and bromolupinine were syn... more Some ester, amide and thioether derivatives of lupinine, aminolupinine and bromolupinine were synthesized and characterized in order to search biologically active compounds. The protonated molecules were studied by tandem mass spectrometry using collision induced dissociation (CID) technique in order to find out how different structural features and functional groups in different quinolizidine derivatives influence fragmentation behavior. Some theoretical calculations were also made to clarify the conformations of neutral and protonated molecules, to reveal the fragmentation routes and the product ions obtained. The functional groups clearly directed the fragmentations although the typical fragments for lupinine were still observed in all the cases. Theoretical calculations were in agreement with observed fragmentations and greatly helped interpretation of the CID spectra.

European journal of …, 1991

... Titre du document / Document title. Some formulation aspects of terfenadine solid dispersions... more ... Titre du document / Document title. Some formulation aspects of terfenadine solid dispersions Auteur(s) / Author(s). BADWAN AA (1) ; ABU-MALOOH A. ; OWAIS L. ; SHEIKH SALEM M. ; ALKAYSI HN ; ARAFAT TA ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s). ...

Biopharmaceutics & Drug Disposition, 2013

ABSTRACTAim: Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogr... more ABSTRACTAim: Clopidogrel is metabolized primarily into an inactive carboxyl metabolite (clopidogrel‐IM) or to a lesser extent an active thiol metabolite. A population pharmacokinetic (PK) model was developed using NONMEM® to describe the time course of clopidogrel‐IM in plasma and to design a sparse‐sampling strategy to predict clopidogrel‐IM exposures for use in characterizing anti‐platelet activity.Methods: Serial blood samples from 76 healthy Jordanian subjects administered a single 75 mg oral dose of clopidogrel were collected and assayed for clopidogrel‐IM using reverse phase high performance liquid chromatography. A two‐compartment (2‐CMT) PK model with first‐order absorption and elimination plus an absorption lag‐time was evaluated, as well as a variation of this model designed to mimic enterohepatic recycling (EHC). Optimal PK sampling strategies (OSS) were determined using WinPOPT based upon collection of 3–12 post‐dose samples.Results: A two‐compartment model with EHC prov...

Food Science and Technology

Chocolate is a preferred food for children and adults. Micronutrient deficiencies are still preva... more Chocolate is a preferred food for children and adults. Micronutrient deficiencies are still prevalent worldwide. This study aims to manufacture and evaluate a type of sugar-free dark chocolate fortified with vitamins and minerals. Three types of chocolate were fortified with vitamin D 3 , vitamin B 12 , and iron and zinc. The fortified chocolate was evaluated in terms of chemical composition using FTIR and DSC methods, visco-mechanical, sensory and stability. The FTIR studies indicated that the spectrum of all fortified chocolates was similar to that of the control, unfortified chocolate. The DSC studies indicated that there were no characteristics differences in crystallinity and degree of crystallization between the fortified and the control products. The addition of vitamins and minerals to chocolate strengthened the structure, increased the melting point, didn't cause significant variation in the rheological properties and had no significant effect on the overall sensation of the taste when compared with controlled chocolate. The stability results indicated that the fortified chocolate was stable for 9 months at room temperature. It was concluded that the fortified chocolate was a good vehicle for the vitamins and minerals with acceptable properties that may be used for supplementing vitamins and minerals.