Faten Farouk

Simultaneous determination of sildenafil citrate and some nitric oxide releasing drugs in human plasma using UPLC MS/MS.

OBJECTIVEnThe inadvertent combination of sildenafil (SLD) and nitric oxide releasing compounds (NRC) may cause a life threatening hypotension and conversion of coital angina into an irreversible one. The aim of this study was to develop and validate a UPLC MS/MS method for the simultaneous quantitative analysis of SLD, nicorandil (NRD), and ARG in human plasma to determine the safety margins for drug combinations.nnnDESIGN AND METHODnChromatographic elution was achieved in 4min using gradient elution and an injection volume of 10μL. Electro-spray positive ionization (ESI+ve) detection and multiple-reaction monitoring mode (MRM) were used for detection.nnnRESULTSnThe method was found to be linear (10-900ng/mL for SLD and NRD while 1-30μg/mL for ARG), accurate and precise (99.35±1.58, 99.62±1.13, and 100.04±1.22% for SLD, NRD and ARG; respectively) and met all other validation requirements.nnnCONCLUSIONnThe developed UPLC MS/MS method is suitable for fast, sensitive, accurate and simultaneous determinations of SLD, NRD, and ARG in plasma.

UPLC-MS/MS Determination of Aceclofenac and Diclofenac in Bulk, Dosage forms and in At-line Monitoring of Aceclofenac Synthesis

Aim: The derivatization product of diclofenac (DCL), aceclofenac (ACL), is a non -steroidal anti-inflammatory drug (NSAID) which causes faster and extended action with reduced gastrointestinal (GI) inflammation. The detection of DCL in ACL bulk and pharmaceutic al products indicates incomplete synthesis and hydrolysis. In this article we have developed a UPLC -MS/MS method for analysis ofACL and DCL. The method was designed as an at-line monitoring tool for process analytical technology (PAT) application to ACLsynthesis. The method was also applied for analysis of ACL and DCL in bulk and tablets. Methodology: Isocratic elution was performed on a UPLC C18 column (2.1 x 50 mm, 1.7 µm) using a mobile phase consisting of acetonitrile, water and formic acid (80:20:0.

Simultaneous UPLC-MS/MS determination of antiepileptic agents for dose adjustment

Therapeutic drug monitoring (TDM) of anti-epileptic drugs (AED) is a routine application. Carbamazepine (CRB) is monitored as the parent drug while oxcarbazepine (OXC) and eslicarbazepine acetate (ESL) are monitored as their active metabolite (eslicarbazepine; MHD). We have developed a UPLC-MS/MS method for determining CRB, OXC, ESL and MHD in plasma or serum with a simplified extraction protocol. The developed method detects sildenafil (SLD), which clinically interferes with AED and is likely to be co-administered in epileptic patients suffering from sexual insufficiency (60%). MHD was prepared in-house. AED were simultaneously determined in presence of SLD using gatifloxacin as an internal standard (IS). Separation was achieved using acetonitrile, methanol and 100u2009mm ammonium acetate in water (32:3:65, v/v/v) on an Intersil® RP-HPLC column (250u2009×u20094.6u2009mm, 5u2009μm). A one-step extraction was performed by simultaneous protein and phospholipids precipitation. Detection was done by tandem mass spectrometry. No relative matrix effect was observed. The method was linear (0.5-40u2009μg/mL for CRB, ESL and MHD and 0.05-4u2009μg/mL for OXC), accurate and selective. Recoveries were 64.41u2009±u20095.07, 45.62u2009±u20091.73, 61.41u2009±u20094.77 and 60.33u2009±u20091.36 for CRB, OXC, ESL and MHD, respectively. The method was successfully applied for TDM of AED.

Simultaneous determination of metformin, vildagliptin, and 3-amino-1-adamantanol in human plasma: Application to pharmacokinetic studies

ABSTRACT Metformin (MET) and vildagliptin (VLD) are coformulated in tablets for the management of diabetes mellitus. The aim of this study is the development of a new fast ultraperformance liquid chromatography method with tandem mass detection (UPLC–MS/MS) for their simultaneous determination with 3-amino-1-adamantanol (starting compound for vildagliptin synthesis; VLI) in human plasma. Separation of MET, VLD, and VLI was performed on a 5 cm UPLC-C18 column using a mobile phase of 0.5% acetic acid in methanol and 0.02 M aqueous ammonium acetate (10:90, v/v). The injection volume was 10 µL and electrospray positive ionization was applied. Extraction from human plasma was carried out by acid precipitation of plasma proteins using pregabalin as an internal standard. The assay was validated according to ICH guidelines. The developed method is valid, fast, and simple and was successfully applied in pharmacokinetic studies in human volunteers. GRAPHICAL ABSTRACT

Effect of Surface Charge and Hydrophobicity Modulation on the Antibacterial and Antibiofilm Potential of Magnetic Iron Nanoparticles

Unmodified magnetic nanoparticles (MNPs) lack antibacterial potential. We investigated MNPs surface modifications that can impart antibacterial activity. Six MNPs species were prepared and characterized. Their antibacterial and antibiofilm potentials, surface affinity, and cytotoxicity were evaluated. Prepared MNPs were functionalized with citric acid, amine group, amino-propyl trimethoxy silane (APTMS), arginine, or oleic acid (OA) to give hydrophilic and hydrophobic MNPs with surface charge ranging from −30 to

Optimized bio-analytical methods development and comparative pharmacokinetic studies of four antidepressants in Egyptian population based on gender difference

The pharmacokinetics (PK) and pharmacodynamics of many oral antidepressants (OADs) vary substantially among different genders and ethnicities. Likewise is their therapeutic effectiveness, time to response and the incidence of adverse drug events. The aim of this study is to compare the PK of four OADs (desvenlafaxine; DSV, venlafaxine; VLX, escitalopram; ESP, and agomelatine; AGT) among Egyptian males and females. In this study, LC-MS/MS methods were developed and validated for determining the four OADs in human plasma. Samples were prepared by liquid-liquid extraction. Chromatographic separation was performed on reversed-phase C18 columns followed by positive-ion electrospray ionization and MS/MS detection. The assays were applied for the assessment of PK parameters in human volunteers (nu202f=u202f95). The developed methods were linear, accurate, and precise for the determination of DSV, VLX, ESP and AGT with extraction recovery of 90u202f±u202f2.0, 98u202f±u202f1.0, 90u202f±u202f1.3 and 87u202f±u202f4.3%, respectively. OADs levels were successfully measured in subjects plasma and PK parameters were calculated. A prevalent inter-individual variation in PK of the studied OAD was observed. The PK profile of DSV, VLX or ESP did not vary significantly between male and female subjects (pu202f=u202f0.07-0.98; confidence level (CL)u202f=u202f95) while the PK of AGT exhibited a significant gender-based variation in both the Cmax and the AUC∞ (pu202f=u202f0.047 and 0.0015; CLu202f=u202f95). Our results highlight the significance of therapeutic drug monitoring of OADs. Further, it indicates the dose adjustment based on gender difference may not be relevant for DSV, VLX and ESP while it may be considered for AGT.

Design and synthesis of novel imidazo[4,5-b]pyridine based compounds as potent anticancer agents with CDK9 inhibitory activity

New imidazo[4,5-b]pyridine derivatives were designed, synthesized and screened for their anticancer activity against breast (MCF-7) and colon (HCT116) cancer cell lines. Nine compounds (I, II, IIIa, IIIb, IV, VI, VIIa, VIII, IX) showed significant activity against MCF-7, while six compounds (I, VIIc, VIIe, VIIf, VIII, IX) elicited a remarkable activity against HCT116. Compounds showing significant anticancer activity revealed remarkable CDK9 inhibitory potential (IC50u202f=u202f0.63-1.32u202fμM) relative to sorafenib (IC50u202f=u202f0.76u202fμM). Moreover, a molecular docking study was performed to illustrate the binding mode of the most active compounds in the active site of CDK9 where it revealed superior binding affinity relative to the natural ligand (T3C).

Bioavailability Enhancement of Aripiprazole Via Silicosan Particles: Preparation, Characterization and In vivo Evaluation

The aim of this study was to design a novel carrier for enhancing the bioavailability of the poorly water-soluble drug, aripiprazolexa0(ARP). Silicosan, the applied carrier, was obtained by chemical interaction between tetraethylxa0orthosilicate (TEOS) and chitosan HCl. Different ARP-loaded silicosan particles were successfully prepared in absence and presence of one ofxa0the followingxa0surfactants; Tween 80, Poloxamer 407 and cetyltrimethylammonium bromide (CTAB). The prepared ARP-loaded silicosan particles were thoroughly investigated for their structures using FTIR, XRD, and DSC analysis as well as their particle size, zeta potential, flowability, drug content, and in vitro drug release efficiencies. The prepared ARP-loaded silicosan particles were characterized by amorphous structure, high drug entrapment efficiency and a remarkable improvement in the release of aripiprazole in simulated gastric fluid. SEM and EDX revealed that the morphology and silica atom content in the preparedxa0ARP-loaded silicosan particles were affected by the used surfactant in their formulations. The selected ARP-loaded silicosan particles were subjected to in vivo study using rabbits. The obtained pharmacokinetic results showed that the relative bioavailability for orally administeredxa0ARP-loaded silicosan particles (SC-2-CTAB) was 66% higher relative to the oral suspension (AUC0-10h was 16.38u2009±u20093.21 and 27.23u2009±u20092.35xa0ng.h/mL for drug powder and SC-2-CTAB formulation, respectively). The obtained results suggested the unique-structured silicosan particles to be used as successful vehicle for ARP.

Dapsone-Loaded Invasomes as a Potential Treatment of Acne: Preparation, Characterization, and In Vivo Skin Deposition Assay.

Dapsone (DPS) is a unique sulfone with antibiotic and anti-inflammatory activity. Owing to its dual action, DPS has a great potential to treat acne. Topical DPS application is expected to be effective in treatment of mild to moderate acne conditions. Invasomes are novel vesicles composed of phosphatidylcholine, ethanol, and one or mixture of terpenes of enhanced percutaneous permeation. In this study, DPS-loaded invasomes were prepared using the thin film hydration technique. The effect of different terpenes (Limonene, Cineole, Fenchone, and Citral) in different concentrations on the properties of the prepared DPS-loaded invasomes was investigated using a full factorial experimental design, namely, the particle size, drug entrapment, and release efficiency. The optimized formulation was selected for morphological evaluation which showed spherical shaped vesicles. Further solid-state characterization using differential scanning calorimetry and X-ray diffractometry revealed that the drug was dispersed in an amorphous state within the prepared invasomes. Finally, the ability of the prepared DPS-loaded invasomes to deliver DPS through the skin was investigated in vivo using wistar rats. The maximum in vivo skin deposition amount of DPS was found to be 4.11xa0mcg/cm2 for invasomes versus 1.71xa0mcg/cm2 for the drug alcoholic solution, representing about 2.5-fold higher for the invasomes compared to the drug solution. The AUC0–10 calculated for DPS-loaded invasomes was nearly 2-fold greater than that of DPS solution (14.54 and 8.01xa0mcg.h/cm2 for the optimized invasomes and DPS solution, respectively). These results reveal that the skin retention of DPS can be enhanced using invasomes.