Maha F. Tutunji

Experimental study and modeling of basic dye sorption by diatomaceous clay

This paper presents a study on the adsorption of basic dye, methylene blue, from an aqueous solution onto diatomaceous earth (diatomite). The effect of initial dye concentrations, adsorbent particle size and concentration, and agitation speed on adsorption was investigated. Adsorption isotherms obtained at different solutions temperatures revealed an irreversible adsorption with a capacity of 42 mmol dye/100 g diatomite reached within 10 min. This value slightly increases with increasing the solution temperature. A proposed correlation to describe the irreversible adsorption isotherm was introduced, which resulted in a better fit to the experimental data than that of Langmuirs and Freundlichs. Two simplified kinetics models, pseudo-first order and pseudo-second order, were tested to investigate the adsorption mechanisms. It was found that the kinetics of adsorption of methylene blue onto the surface of diatomite at different operating condition are best described by the pseudo-first-order model.

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies

A sensitive, specific and selective liquid chromatography/tandem mass spectrometric method has been developed and validated for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on a reverse phase C(18) column (50mmx4mm, 3microm) using water with 2.5% formic acid, methanol and acetonitrile (40:45:15, v/v/v (%)) as a mobile phase (flow rate of 0.70mL/min). Irbesartan and hydrochlorothiazide were ionized using ESI source in negative ion mode, prior to detection by multiple reaction monitoring (MRM) mode while monitoring at the following transitions: m/z 296-->269 and m/z 296-->205 for hydrochlorothiazide, 427-->175 for irbesartan. Linearity was demonstrated over the concentration range 0.06-6.00microg/mL for irbesartan and 1.00-112.00ng/mL for hydrochlorothiazide. The developed and validated method was successfully applied to a bioequivalence study of irbesartan (300mg) with hydrochlorothiazide (12.5mg) tablet in healthy volunteers (N=36).

Simultaneous determination of bisoprolol and hydrochlorothiazide in human plasma by HPLC coupled with tandem mass spectrometry

A sensitive, specific and selective method has been developed for the simultaneous determination of bisoprolol and hydrochlorothiazide in human plasma. The method employed a state of the art LC-MS/MS operated in the positive and negative ionization switching modes. A simple sample preparation step involving protein precipitation with acetonitrile has been optimized; the analytes and the internal standard moxifloxacin were separated on a Purosphere STAR C8 column (125 mm x 4 mm, 5 microm). The mobile phase was an ammonium acetate solution (1 mM) with formic acid (0.2%): methanol and acetonitrile (65:17.5:17.5, v/v/v (%)), the flow rate was set at 0.65 mL/min. Bisoprolol and hydrochlorothiazide were ionized using ESI source prior to detection by Multiple Reaction Monitoring (MRM) mode while monitoring at the following transitions: positive m/z 326-->116 for bisoprolol, negative m/z 296-->269 and m/z 296-->205 for hydrochlorothiazide. Linearity was demonstrated over the concentration range 0.10-30.0 (ng/mL) for bisoprolol and 1.00-80.00 ng/mL for hydrochlorothiazide. The limits of detection were 0.100 (ng/mL) for bisoprolol and 1.00 (ng/mL) for hydrochlorothiazide. The validated method was successfully applied to a pharmacokinetic study of 5 mg bisoprolol fumarate with 12.5 mg hydrochlorothiazide tablet in healthy volunteers.

Indirect trace determination of ethylenediaminetetraacetic acid (EDTA) in water by potentiometric stripping analysis

Abstract An analytical method for indirect trace determination of ethylenediaminetetraacetic acid (EDTA) in water, by potentiometric stripping analysis is described. Excess Bi(III) was added to form a 1:1 complex with EDTA at pH 2.3. The uncomplexed Bi(III) was then deposited on a glassy carbon electrode at a potential of −0.40 V vs. SCE and subsequently stripped potentiometrically using potassium dichromate as oxidant. The stripping time of uncomplexed Bi(III) was recorded. The Concentration of EDTA in the sample was determined from the concentration of added Bi(III) and the potentiometrically stripped Bi(III) at −0.4 V by the standard addition method. The relative standard deviation for EDTA concentration of 95 ppb and 4.5 ppb was 1.9% and 2.6%, respectively. The detection limit was about 1 ppb EDTA for a deposition time of 3 minutes.

Possible Interethnic Differences in Omeprazole Pharmacokinetics Comparison of Jordanian Arabs with Other Populations

Background and objectiveConsiderable ethnic differences have been reported in the incidence of the poor metaboliser (PM) genotype of cytochrome P450 (CYP) 2C19. The frequency of this genotype was found to be much higher in Oriental persons (13–23%) than in American or European populations (3–5%). There are, however, no valid data published for Arabic subjects. The present study was conducted to evaluate pharmacokinetic parameters of omeprazole after a single dose in healthy Jordanian Arabic subjects and to compare the results with data published for other populations.MethodsSeventy-four healthy male Jordanian Arabic volunteers contributed to the study, which was performed at A1 Essra Hospital in Amman, Jordan. After an overnight fast, omeprazole was administered as a single Losec® 20mg capsule. A total of 20 blood samples were collected over a 10-hour period after administration. Omeprazole pharmacokinetic parameters were determined from the plasma concentration-time profiles using the WinNonlin software. Kolmogorov-Smirnov’s test and probit plots of omeprazole area under the plasma concentration-time curve (AUC) data were used to analyse the frequency distribution of phenotypic data.ResultsThe mean pharmacokinetic parameters and their corresponding coefficient of variation (CV%) for peak plasma concentration (Cmax), AUC from time zero to infinity (AUC∞), time to reach Cmax (tmax), apparent oral clearance (CL/F) and elimination half-life (t1/2) were 314.96 ng/mL (56%), 923.2 ng · h/mL (108.6%), 2.1h (44%), 0.66 L/h/kg (92%) and 1.5h (56.6%), respectively. Inter-individual differences in the current study were high for all pharmacokinetic parameters, yet comparable to CVs reported in nonphenotyped subjects identified within other ethnic groups (40.3–159% for AUC and 39–48.2% for Cmax).The frequency distribution of all parameters, particularly the AUC, was shown to be trimodal. This has proposed the presence of three distinct phenotypes, designated as extensive metabolisers (EMs), slow-extensive metabolisers (SEMs), and PMs, with corresponding frequency of 36.5%, 39.2% and 24.3%, respectively. After stratification, the relative mean AUCs of omeprazole in EMs, SEMs and PMs were 1: 2.7: 9.3 (all p < 0.001). Accordingly, the CL/F of omeprazole showed a ratio of 9.8 : 3.6: 1 for three phenotype groups, respectively. For other pharmacokinetic parameters including Cmax, t1/2, AUC normalised for bodyweight (AUCN), Cmax/dose and AUC/dose, there were also significant differences between the three groups.ConclusionsThe current pharmacokinetic study revealed that the majority of the Jordanian Arabics seemed to be more properly classified within the EM phenotype. More specifically, the observed metabolic rates of heterozygous and homozygous Jordanian Arabic EMs were more comparable to those of Caucasian EMs than Oriental EMs. Consequently, higher dosage requirements can be expected among most of the Jordanian Arabics. Yet, the incidence of PMs is significant and they seemed to exhibit a similar pharmacokinetic pattern to Chinese PMs in terms of long-term exposure (clearance and AUC) as well as short-term exposure (Cmax) parameters, after adjustment for dose and bodyweight.Therefore, further clinical application of CYP2C19 polymorphism is anticipated in Jordanian Arabic mixed population, particularly if long-term use of omeprazole is intended.

Simple rapid method for the determination of dissolved oxygen by potentiometric stripping analysis

A method is described for the determination of dissolved oxygen in natural water by potentiometric stripping analysis. Oxygen standards are prepared by the reaction of permanganate with peroxide and are used to oxidise the Cd-Hg formed at the glassy carbon electrode from a standard solution of Cd2+. The quantitative reduction in the stripping time is used to measure the oxygen concentration in the water. The method is simple and rapid, with a higher correlation coefficient between added and measured oxygen levels than is obtainable using the Winkler procedure. The use of the method in acidic solutions is also an advantage for the measurement of dissolved oxygen in natural and waste waters.

Dissolved oxygen: method comparison with potentiometric stripping analysis

Abstract Three methods for determination of dissolved oxygen in samples of natural water are compared; patentiometric stripping analysis, PSA compares well with oxygen selective electrodes. Although potentiometric stripping analysis and oxygen selective electrode methods are found to be simple, rapid and of higher reproducibility than the usual Dinkier procedure, the use of oxygen selective electrodes has many disadvantages.

Reversing the adverse biochemical effects in lead-intoxicated rats by N,N`- bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine

N,N`-Bis[(1,2-didehydro-1-hydroxy-2-thioxopyrid-4-yl)-carbonyl]- L-lysine (HTPL) is a novel newly synthesized compound intended to be used for the chelation of lead in intoxicated animals. Subchronic lead intoxication experiments were carried out on Wistar male rats; these rats were intoxicated with lead and then treated with HTPL. Results were compared with those obtained with known compounds used for lead chelation therapy, such as disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA), using different routes of administration. Biological samples of whole blood and urine were collected and analyzed for urinary proporphyrins, δ-aminolevulinic acid dehydratase, and zinc protoporphyrin. Results revealed that HTPL can remarkably reverse the toxic effects of lead intoxication at biochemical levels. Additionally, results showed that this agent is as good or even more potent than calcium disodium ethylnediaminetetraacetic acid (CaNa2EDTA) and meso-2,3-dimercaptosuccininc acid (DMSA) in reversing the toxic effect of lead. More importantly, HTPL was found effective when administrated intraperitoneally and orally.

Importance of metabolite data in bioequivalence studies - Sample size and power

I air quality and biomass smoke within indigenous communites is an emerging topic of significant public health concern. Wood stove use is highly prevalent within many reservation communities and biomass smoke associated with cooking and heating has been associated with chronic health problems. Studies conducted in rural and Native American communities examining indoor levels of fine particulate matter (PM2.5) have frequently found levels that exceeded current health-based air quality standards. Native elderly populations are particularly susceptible to reduced lung function or chronic conditions such as asthma, COPD, and bronchitis. Research conducted by our team has demonstrated that improving the efficacy of household level interventions (e.g., air filtration units) can reduce indoor exposures to biomass smoke and therefore lead to improved health outcomes. The findings from these interventions and qualitative input from wood stove experts, suggests that education interventions related to demonstrated best-practices in wood stove operation and fuel efficiency can translate to low-cost and sustainable strategies for reducing indoor biomass combustion exposures. This recently funded project is guided by community-based participatory research principles in order to create more effective and culturally centered intervention methods to improve indoor air quality. The household level intervention is coupled with a community level intervention that was developed and initiated by tribal stakeholders. This presentation will provide information about environmental concerns within indigenous communities and describe the initial work to culturally adapt the approaches and initial intervention planning. The presentation will seek to advance knowledge regarding community-based efforts to increase the translational public health impact of indoor air quality educational materials and interventions.A important requirement of emergent therapeutics will be the development of pharmaceutical technologies suitable for sustained and preventive health care in remote and sub-optimal environmental conditions. Availability of sustained, stable and targeted delivery of pharmaceuticals for preventive health of major organ systems including gastrointestinal, hepatorenal, musculo-skeletal and immune function are essential for effective pharmacotherapeutics. Specifically, pharmaceutical demands may include multi-drug combinations for hormone replacement, radiation protection, immune enhancement and organ function restoration. Additionally, extended stability of pharmaceuticals dispensed must be also considered in future drug development. Emerging technologies that can deliver stable and multi-therapy pharmaceutical preparations and delivery systems include nanotechnology based drug delivery platforms, targeted-delivery systems in non-oral and non-parenteral formulation matrices. Synthetic nanomaterials designed with molecular precision offer defined structures, electronics, and chemistries to be efficient drug carriers with clear advantages over conventional materials of drug delivery matricies. Nanocarrier materials like the bottle brush polymers may be suitable for systemic delivery of drug cocktails while Superparamagnetic Iron Oxide Nanoparticles or (SPIONS) have great potential to serve as carriers for targeted drug delivery to a specific site. These and other emerging concepts of drug delivery and extended shelf-life technologies will be reviewed in light of their application to address health-care challenges of the future. Innovations in alternate treatments for sustained immune enhancement and infection control will be also discussed.In the present study, we did the non -compartmental pharmacokinetics study of amlodipine using high performance liquid chromatography with ultraviolet detector (HPLC-UV) in wistar rats. Rats were allocated to two groups; intravenous group (IV study n=6) and oral group (PO study n=6).In both groups, surgical procedures were carried out under Ketamine HCL (40 mg/kg) and Diazepam (1.5mg/kg) general anesthesia (intramuscular injection).The blood samples were collected at different time interval and were analyzed using HPLC-UV system. Results showed that Amlodipine had a short terminal half-life with relatively high distribution volumes during the steady and terminal phases, and with low plasma clearance. Furthermore, the availability ratio of amlodipine through the intravenous route was higher than that through the oral route, indicating that first pass metabolism and hepatic blood flow are important factor of drug elimination of amlodipine. Bioavailability was estimated to be 78.60 ± 21.33% based on the AUCinf ratios of oral and intravenous administration.R advances in genomics technologies exert profound impact on the biomedical sciences. The main goal of the pharmaceutical sciences is to understand individual differences in drug response and toxicity, as a foundation for developing and guiding therapy for each patient. Bioavailability and bioequivalence represent important factors in the design of optimal drug therapy. Both genetic variants and epigenetic factors, and interplay between them, determine a portion of inter-individual variability, with expression of drug metabolizing enzymes (DMEs) and transporters playing a key role. A number of genetic variants have already been incorporated into pharmacogenetic biomarker tests, but the vast majority of (epi) genetic variability remains hidden. We have implemented gene-by-gene and genome-wide methods to search for pharmacologically relevant variants and regulatory processes, using next generation sequencing of DNA and RNA (RNAseq of coding and non-coding RNAs). A survey of DME and transporter expression reveals distinct expression profiles in various tissues, and the presence of multiple RNA transcripts at each gene locus (such as splice variants). Broad understanding of the regulation of DMEs and transporters has the potential to guide drug development and clinical application.

Chemical and Structural Properties of Jordanian Diatomaceous Clay Supported Metal Oxides

Abstract Metal oxides of titanium, vanadium, manganese and iron were deposited on the native Jordanian diatomaceous clay. The chemical and structural properties of the prepared samples were investigated using SEM, XRF, ICP, XRD and FTIR techniques. The diatomaceous clay supported metal oxides were used in preliminary experiments to explore their interaction with aqueous phenol solution under thermal and photochemical conditions, in the presence and absence of hydrogen peroxide. The results showed that the metal oxides have interacted with the diatomaceous clay and caused some structural changes. These were reflected in the surface area of the samples and their activity in the phenol reactions.