Durisehvar Unal - Academia.edu (original) (raw)

Papers by Durisehvar Unal

MARMARA PHARMACEUTCAL JOURNAL, 2011

Journal of Child Neurology, Jun 1, 2007

Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease... more Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.

Optics and Spectroscopy, Aug 1, 2015

A sensitive spectrofluorimetric method was developed for the determination of famciclovir in pure... more A sensitive spectrofluorimetric method was developed for the determination of famciclovir in pure and pharmaceutical preparations. The method is based on the derivatization reaction of famciclovir with fluorescamine. The different experimental parameters that affect the fluorescence intensity were carefully studied, at once. The method was validated for linearity, limit of detection, limit of quantification, precision, accuracy, recovery, robustness. The assay was linear over the concentration range of 100 and 1000 ng/mL. The limits of detection and limit of quantification were calculated to be 51.13 and 153.39 ng/mL. The proposed method was applied to study of famciclovir in pure and in pharmaceutical preparations.

Journal of Faculty Pharmacy of Istanbul University, 2012

SUMMARY Sensitive spectrophotometric method was developed for the determination of mirtazapine fr... more SUMMARY Sensitive spectrophotometric method was developed for the determination of mirtazapine from pharmaceutical preparats. The proposed method was based on the formation of a yellow colored ion-pair complex by the reaction of methyl orange with mirtazapine. The ion pair complex was extracted with dichloromethane. Under the optimum condition, the ion pair complex showed an absorption maximum at 427 nm. The linearity range for concentrations of mirtazapine was found to be 2.5-12.5 I¼g/mL. The proposed method is successfully applied to the determination of mirtazapine tablet formulations. OZET Mirtazapinin farmasotik preparatlarda tayini icin duyarli spektrofotometrik bir yontem gelistirilmistir. Gelistirilen yontem, mirtazapin ile metil oranj arasinda sari renkli iyon cifti kompleksi olusturmasi esasina dayanmaktadir. Iyon cifti kompleksi diklormetan ile ekstre edilmistir. Optimize edilmis kosullarda iyon cifti kompleksinin maksimum absorbsiyon degeri 427 nm olarak tespit edilmisti...

European Journal of Drug Metabolism and Pharmacokinetics, Aug 29, 2020

İstanbul Journal of Pharmacy

Background and Aims: A sensitive, accurate and precise method has been developed for the determin... more Background and Aims: A sensitive, accurate and precise method has been developed for the determination of Capsaicin from pain patches by Gas chromatography Mass Spectrometry (GC-MS). Capsaicin has irritant effects in high concentrations, so these effects can be minimized by knowing the amount present in pain patches for the efficacy and safety of patches. Methods: Capsaicin was extracted by using liquid-liquid extraction from patches. The Gas Chromatographic separation was performed by using 5% diphenyl 95% dimethylpolysiloxane column with high a purity 2 mL/min flow rate helium gas. The separation was made with a gradient oven temperature program. The oven temperature started at 250°C and was increased to 275°C at 10°C.min-1 ramp rate and held at 275°C for 2.5 min. The injection port was adjusted at 300°C and a split injection mode was used. The analysis was carried out in a split mode of 5:1. MS ionization potential was determined at 70 eV. Results: The calibration curve was found to be linear in the range 5-50 μg/mL. The limits of detection and quantification for capsaicin was found to be 3.46 μg/mL and 5 μg/mL, respectively. The method developed was validated and successfully applied to the patch analysis. Conclusion: This method is simple, reproducible, and can be used safely for the routine analysis of Capsaicin without derivatization. This study has the potential how to calculate the Scoville Heat Units (SHU) of pain patches that contain Capsaicin. The amount of Capsaicin in the pain patch, its irritant effects, and its efficacy and safety appear to be low when evaluated by the SHU.

Chemistry and Materials Research, 2020

Personalized therapy (PM) has the potential to adapt treatment with the best response and highest... more Personalized therapy (PM) has the potential to adapt treatment with the best response and highest safety to provide better patient care. Key data is drug concentration of biological materials such as plasma and serum.Individual drug therapy means, choice of a drug and its dose regime should fit every individual specifically. Thus efficacy of a drug treatment would improve significantly. When developing an analytical method for (Therapeutic drug monitoring) TDM, it is important to choose a clinically relevant calibration range. This quantitation range should be built around the proposed target concentration, covering majority of samples as seen in the clinic (Ciocan-Cartita et al. 2019).Inter-individual variability in Pharmacokinetic variables may affect the blood concentration of drug so TDM approaches could solve the dosing problem.To achieve individual drug therapy with a reasonably predictive outcome, one must further account for different patterns of drug response among geographically and ethnically distinct populations.

Scientific reports, Jan 2, 2017

Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon exten... more Administration of first-in-class anti-EGFR monoclonal antibody cetuximab is contingent upon extensive pharmacogenomic testing. However in addition to tumor genomics, drug exposure levels could play a critical, yet largely underestimated role, because several reports have demonstrated that cetuximab pharmacokinetic parameters, in particular clearance values, were associated with survival in patients. Here, we have developed an original bioanalytical method based upon the use of LC-MS/MS technology and a simplified sample preparation procedure to assay cetuximab in plasma samples from patients, thus meeting the requirements of standard Therapeutic Drug Monitoring in routine clinical practice. When tested prospectively in a pilot study in 25 head-and-neck cancer patients, this method showed that patients with clinical benefit had cetixumab residual concentrations higher than non-responding patients (i.e., 49 ± 16.3 µg/ml VS. 25.8 ± 17 µg/ml, p < 0.01 t test). Further ROC analysis sh...

Journal of the Turkish Chemical Society Section A: Chemistry

Cytarabine (Cyt) (also known as cytosine arabinoside (ara-C)) used in the treatment of acute myel... more Cytarabine (Cyt) (also known as cytosine arabinoside (ara-C)) used in the treatment of acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL). CYT applied in high doses for treatment can cause renal failure. Monitoring excreted urine drug levels can help kidney failure. For this reason, a method was developed and validated by HPLC-MSMS for urine CYT analysis, which is not included in the literature. In this study, a liquid chromatography (HPLC) with triple quadrupole Mass Spectrometric (MS/MS) method developed for the determination of Cyt from urine for toxicokinetic evaluation. Positive MRM mode selected for the quantification of Cyt. The product and major fragment ion for Cyt 244.0 > 112.0 m/z, for IS 198.0 > 152.0 m/z. The optimal MS parameters for Cyt and IS are as follows Fragmentor 80 V, 70 V, Collision energy, 6, 9 respectively. A novel simple, high-throughput and highly sensitive HPLC-MS/MS method was successfully developed and validated for the determination o...

Background and Aims: The combination of troxerutin and carbazochrome has been found efficacious f... more Background and Aims: The combination of troxerutin and carbazochrome has been found efficacious for non-surgical patients with acute uncomplicated hemorrhoids. Therefore it is essential to develop a simultaneous analysis method of those drug substances. This study explains a simple and selective HPLC method to analyze troxerutin and carbazohrome in tablets. Methods: The analysis was carried out using a core-shell pentafluorophenyl propyl polar column with a mobile phase consisting of (MeOH; % 5 HAc), (99.5:0.5 - V/V) at a flow rate of 0.25 mL/min. UV detection was set to 350 nm. Results: The standard calibration curve was established between 1.00-20.00 μg/mL for troxerutin; 0.05-1.00 μg/mL for carbazochrome. LOD and LOQ were found to be 0.65 μg/mL and 1.00 μg/mL for troxerutin and 0.01 μg/mL and 0.05 μg/mL for carbazochrome, respectively. Conclusion: The proposed method was validated for specificity, linearity, accuracy, precision, LOQ and LOD and then successfully applied for the a...

Hoje e uma tarde de sabado, 11.07.2020, mais um dia que estou em quarentena, como todos nos, agua... more Hoje e uma tarde de sabado, 11.07.2020, mais um dia que estou em quarentena, como todos nos, aguardando uma solucao para o COVID. Vejo na Academia os Confrades apresentando lives, discutindo problemas dos mais relevantes na area trabalhista e com enfoque no social, na defesa dos mais sofridos com essa pandemia, e evidentemente me orgulho desse trabalho tao relevante que presta a Academia ao Direito do Trabalho e ao pais.Verificamos nesse tempo, desde marco, que certamente existiram milhares de demissoes, empregados sem trabalho e sem dinheiro para sustentacao deles e da familia, empresas fechando as portas e a economia despencando. Tudo fruto de algo que pegou o mundo de surpresa

TURKISH JOURNAL OF CHEMISTRY, 2019

Curcuminoids, reported to have important biological properties, such as antioxidant, anti-Alzheim... more Curcuminoids, reported to have important biological properties, such as antioxidant, anti-Alzheimer, and antidiabetic properties, comprise curcumin (CRM; 1,7-bis [4-hydroxy-3-methoxyphenyl]-1,6-heptadiene-3,5-dione) and its derivatives demethoxycurcumin (DMC; (E,6E)-1-(3,4-dimethoxy-cyclohexyl)-7-(3,4-dimethoxyphenyl)hepta-1,6-diene-3,5dione) and bisdemethoxycurcumin (BDMC; 1,7-bis[4-hydroxyphenyl]-1,6-heptadiene-3,5-dione). Their electrochemical oxidations are thoroughly explored by applying cyclic and differential pulse voltammetric techniques. The dependence of current intensities and potentials on pH, concentration, scan rate, and nature of the buffer was investigated. The outcome is supported by density functional theory computations indicating the transfer of 4-e − /H + , 6-e − /H + , and 8e − /H + couples involved in the oxidation mechanisms of CRM, DMC, and BDMC, respectively, leading to the formation of the same oxidized product.

International Journal of Pharmaceutics, 2018

The Journal of Clinical Pharmacology, 2012

European Journal of Drug Metabolism and Pharmacokinetics, 2009

Flurbiprofen (CAS 5104-49-4) is a member of phenylalkanoic acid derivative group of nonsteroid an... more Flurbiprofen (CAS 5104-49-4) is a member of phenylalkanoic acid derivative group of nonsteroid anti-inflammatory drugs. It exhibits anti-inflammatory, analgesic and antipyretic activities. Two different tablets containing flurbiprofen (FLU) were investigated in 24 healthy volunteers to prove the bioequivalence between both treatments after single oral dose administrations. Fluroben 100 mg tablet and 100 mg tablet of the originator product were used as test and reference preparation respectively. The study was performed open label, randomized, two period cross-over design with 15 days wash out period. Blood samples were taken up to 24 hours for pharmacokinetic profiling. The plasma concentrations of flurbiprofen were determined with validated HPLC-UV method. Maximum plasma concentration (Cmax) of FLU 19,143.65 ng/ml and 19,164.22 ng/ml were found for test and reference formulation respectively. Areas under the plasma concentration time curve AUC(0-infinity), of 118 501.4 ng.h/ml and 111,339.8 ng.h/ml were calculated test and reference formulation respectively. Primary target parameters AUC (0-infinity) and Cmax, both of them were tested parametrically by analysis of variance (ANOVA); 90% confidence intervals were between 100.5%-111.18% for AUC(0-infinity), and 87.6%-115.0% for Cmax. All these values were within the acceptance range (80%-125%) for bioequivalence studies.

Cellular Signalling, 2010

The Wnt signaling pathway is involved in many differentiation events during embryonic development... more The Wnt signaling pathway is involved in many differentiation events during embryonic development and Received 8 March 2010 can lead to tumor formation after aberrant activation of its components. β-catenin, a cytoplasmic

Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is no... more Cryptochromes are negative transcriptional regulators of the circadian clock in mammals. It is not clear how reducing the level of endogenous level of the CRY1 in mammals will affect circadian rhythm and the relation of such a decrease with apoptosis is unknown. Here, we discovered a molecule that destabilizes Cryptochrome 1 (CRY1) both in vitro and in vivo. The small molecule, called M47, selectively enhanced the degradation rate of CRY1 by increasing its ubiquitination and the period of U2OS Bmal1-dLuc cells. In addition, subcellular fractionation studies from mice liver indicated that M47 enhanced degradation rate of the CRY1 level in the nucleus. Furthermore, M47-mediated CRY1 reduction enhanced cisplatin-induced apoptosis in Ras-transformed p53 null fibroblast cells. Finally, systemic repetitive administration of M47 increased the median lifespan of p53−/− mice by ~25%. Collectively our data suggest that M47 is a very promising molecule to treat forms of cancer depending on the...

International Journal of Scientific and Technological Research, 2018

An isocratic HPLC method has been developed for simultaneous determination of paracetamol-acetami... more An isocratic HPLC method has been developed for simultaneous determination of paracetamol-acetaminophen (PAR) and flurbiprofen (FLU) in pharmaceutical preparations. The method was based on separation by using a mobile plase acetonitrile– 0.1M sodium acetate solution (pH:5.00) (60:40,v/v) and reversed-phase C18 column. The mobil plase flow rate was 0.8mL/min with UV detection at 247nm. The linearity ranges were 0.1-1.5 μg/mL for PAR and FLU. The limits of detection and quantification were found to be 16.33 ng/mL and 54.45 ng/mL for PAR and 15.25 ng/mL and 50.82 ng/mL for FLU, respectively. The combination of these two drugs has not commercially avaible but patented as combined preparation. The proposed method was successfully validated and applied to the determination in pharmaceutical preparations. The developed and validated method is simple, sensitive and reproducible and can be used safely routine simultaneous analysis of PAR and FLU in pharmaceutical preparations in the future. ...