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2. Development and UV-VIS Spectrophotometric analysis of an ease-of-use pediatric oral solution of dexamethasone for personalized therapies.

Author

ENEŞ, Duygu, FİDAN, Bilge Başak, KAPLAN, Ozan, DOGAN, Aysegul, ALTINÖZ, Sacide, ÇELEBİER, Mustafa, and KAYNAK, Mustafa Sinan

Subjects
MEDICAL personnel, INDIVIDUALIZED medicine, HOSPITAL pharmacies, QUALITY control, DEXAMETHASONE
Abstract

The usage of dexamethasone for pediatric applications is a well-known issue. In the present study, we developed an oral dexamethasone solution formulation especially aimed for dose-dependent personalized therapies and having excipients known as not harmful to be safely used in pediatrics. The aim of this study was to prepare an easy-ofuse pediatric oral solution of dexamethasone and develop an UV/VIS Spectrophotometric method for the evaluation of the stability and quality control of the developed formulation. The primary source of dexamethasone for preparation of the oral pediatric solution was the dexamethasone one-time injectable solutions. This allowed the formulation to be easily prepared in basic laboratory conditions. Dexamethasone content and stability of the formulation were ensured by quantification using the developed UV/VIS Spectrophotometric method validated based on ICH Q2 (R1) guidelines. Simple, fast, reliable, and validated spectrophotometric analysis of dexamethasone was carried out at 269 nm wavelength and the method was linear in a range of 1.00 to 50.00 µg mL-1. The developed formulation was stable at 4 °C at least for three weeks when protected from daylight. The other stability conditions (ambient temperature and -20 °C) were also evaluated for the assays. Although the methodology used in this study contains simple processes which can be easily adapted to basic laboratory conditions, the results were satisfactory to prepare an ease-of-use pediatric oral solution of dexamethasone for personalized medicine. The validated UV/VIS Spectrophotometric method was selective for the formulation and easily applied for the quality control and stability studies of the samples. Such formulations could be helpful for health professionals in managing real-life corticosteroid treatment application problems especially for pediatrics in hospital pharmacy. [ABSTRACT FROM AUTHOR]

Published
2024
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3. A Facile and Efficient Protocol for Phospholipid Enrichment in Synovial Joint Fluid: Monodisperse-Mesoporous SiO 2 Microspheres as a New Metal Oxide Affinity Sorbent.

Author

Aladağ, Serhat, Demirdiş, İlayda, Gökçal Kapucu, Burcu, Koç, Emine, Kaplan, Ozan, Aktaş, Batuhan Erhan, Çelebier, Mustafa, Tuncel, Ali, and Korkusuz, Feza

Subjects
JOINTS (Anatomy), ARTICULAR cartilage, SYNOVIAL fluid, GRADIENT elution (Chromatography), SOLID phase extraction
Abstract

Phospholipids (PLs), essential components of cell membranes, play significant roles in maintaining the structural integrity and functionality of joint tissues. One of the main components of synovial joint fluid (SJF) is PLs. Structures such as PLs that are found in low amounts in biological fluids may need to be selectively enriched to be analyzed. Monodisperse-mesoporous SiO2 microspheres were synthesized by a multi-step hydrolysis condensation method for the selective enrichment and separation of PLs in the SJF. The microspheres were characterized by SEM, XPS, XRD, and BET analyses. SiO2 microspheres had a 161.5 m2/g surface area, 1.1 cm3/g pore volume, and 6.7 nm pore diameter, which were efficient in the enrichment of PLs in the SJF. The extracted PLs with sorbents were analyzed using Q-TOF LC/MS in a gradient elution mode with a C18 column [2.1 × 100 mm, 2.5 μM, Xbridge Waters (Milford, MA, USA)]. An untargeted lipidomic approach was performed, and the phospholipid enrichment was successfully carried out using the proposed solid-phase extraction (SPE) protocol. Recovery of the SPE extraction of PLs using sorbents was compared to the classical liquid–liquid extraction (LLE) procedure for lipid extraction. The results showed that monodisperse-mesoporous SiO2 microspheres were eligible for selective enrichment of PLs in SJF samples. These microspheres can be used to identify PLs changes in articular joint cartilage (AJC) in physiological and pathological conditions including osteoarthritis (OA) research. [ABSTRACT FROM AUTHOR]

Published
2024
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6. Plasma metabolomics for diagnostic biomarkers on ectopic pregnancy.

Author

Kaplan, Ozan, Ertürk Aksakal, Sezin, Fidan, Bilge Başak, Engin-Üstün, Yaprak, and Çelebier, Mustafa

Subjects
*ECTOPIC pregnancy, *TIME-of-flight mass spectrometry, *METABOLOMICS, *PREGNANT women, *GRADIENT elution (Chromatography), *BIOMARKERS
Abstract

Metabolomics is a relatively novel omics tool to provide potential biomarkers for early diagnosis of the diseases and to insight the pathophysiology not having discussed ever before. In the present study, an ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) was employed to the plasma samples of Group T1: Patients with ectopic pregnancy diagnosed using ultrasound, and followed-up with beta-hCG level (n = 40), Group T2: Patients with ectopic pregnancy diagnosed using ultrasound, underwent surgical treatment and confirmed using histopathology (n = 40), Group P: Healthy pregnant women (n = 40) in the first prenatal visit of pregnancy, Group C: Healthy volunteers (n = 40) scheduling a routine gynecological examination. Metabolite extraction was performed using 3 kDa pores - Amicon® Ultra 0.5 mL Centrifugal Filters. A gradient elution program (mobile phase composition was water and acetonitrile consisting of 0.1% formic acid) was applied using a C18 column (Agilent Zorbax 1.8 μM, 100 x 2.1 mm). Total analysis time was 25 min when the flow rate was 0.2 mL/min. The raw data was processed through XCMS – R program language edition where the optimum parameters detected using Isotopologue Parameter Optimization (IPO). The potential metabolites were identified using MetaboAnalyst 5.0 and finally 27 metabolites were evaluated to be proposed as potential biomarkers to be used for the diagnosis of ectopic pregnancy. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Development of an RP-HPLC method to evaluate the basic characteristics of talazoparib-loaded PLGA nanoparticles.

Author

Topçu, Beril Taş, Kaplan, Ozan, Pehlivan, Sibel Bozdağ, Çelebier, Mustafa, and Öner, Levent

Subjects
*DRUG delivery systems, *LIQUID chromatography, *HIGH performance liquid chromatography, *BRAIN cancer, *POLY(ADP-ribose) polymerase, *POLY ADP ribose
Abstract

The use of poly (ADP-ribose) polymerase (PARP) inhibitors for cancer treatment has been reported previously. Talazoparib is a PARP inhibitor, and its solubility problems encouraged us to prepare talazoparib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles for use in brain cancer models. To determine the encapsulation efficiency and release profile, a reversed-phase high-pressure liquid chromatography (RP-HPLC) method was developed and validated. A Shiseido 5 µm C18 100 Å column (250 x 4.6 mm) was used with a flow rate of 1.0 mL/min. Isocratic elution was performed using an acetonitrile:phosphate buffer (100 mm, pH 6.25) (35:65 v/v) mixture. The injection volume was 5 μL and UV detection was performed at 227 nm. The method was linear within the range from 0.1 to 12.5 µg/mL. The encapsulation efficiency and release profile of the prepared formulation were analyzed using the developed RP-HPLC method, and it was found that the encapsulation efficiency was 65.17% ± 0.50 and the release of the talazoparib was around 40% within 5 h and remained stable for 25 h. The RP-HPLC method developed in the present study can be adapted for further applications to determine talazoparib in its commercial formulations and proposed encapsulated drug delivery systems. [ABSTRACT FROM AUTHOR]

Published
2024
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8. RP-HPLC method combined with ultrafiltration for simultaneous analysis of Melphalan and Topotecan in human plasma samples.

Author

Kaplan, Ozan, Yılmaz, Nergiz, Uçar, Büşra, Algedik, Merve Özge, Koç, İrem, Kıratlı, Hayyam, and Çelebier, Mustafa

Subjects
*GRADIENT elution (Chromatography), *BLOOD plasma, *BLOOD proteins, *ANTINEOPLASTIC agents, *TOPOTECAN
Abstract

Pharmaceutical analysis still attracts the attention of researchers, and pharmaceutical analysis methods specific to the purpose of the application are needed in routine applications. In this study, the RP-HPLC method was developed for the simultaneous analysis of two different cancer drugs from human blood plasma due to simultaneous use. Melphalan and topotecan are licensed drugs that have been used for a long time. In routine practice, the simultaneous use of these two drugs is limited. However, studies have found that two active substances were used together in high-dose chemotherapy applications. This situation encourages the development of methods for the simultaneous analysis of both active substances in spiked human blood plasma samples. In this study, melphalan and topotecan were analyzed by RP-HPLC in 17 minutes, including post-run, with a gradient elution program using a Superco 5 µm C18 100 Å LC Column (100 x 4.6 mm) when the flow rate was 1.0 mL min-1. The method was linear in the 1.0- 20.0 µg/mL range for both active substances. The detection wavelength was 261 nm. The accuracy and precision of the validated analytical method were demonstrated through intraday and interday studies. The analyte was freed from the remaining plasma components due to filtering the supernatant (after precipitation of the plasma proteins with methanol) with an ultrafilter (having 10 kDa pores). The simple methodology used in this study can be easily adapted to any pre-clinical or clinical application where analysis of melphalan and topotecan in plasma is required. [ABSTRACT FROM AUTHOR]

Published
2024
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11. Spectrophotometric Methodologies Applied for Determination of Pharmaceuticals

Author

Jangra Surender, Hu Jianping, Bhakri Gaurav, Luo Qing, Mazumder Rupa, Liu Jiang, Duan Huai-Chuan, Yuen Lew Sze, Wan Hua, Zhao Gang, Nie Lixing, K. Sharma Raj, Wei Lim Lee, Ağin Fatma, Gan Ya, Pothuraju Ramesh, Padhi Swarupanjali, Shi Hu-Bing, Li Shiying, Peng Lianxin, Cai Shaohui, Kaplan Ozan, Gan Xia, Sun Xin, Jiang Zhounan, Kumar Kashyap Pankaj, Lin Teoh Seong, Qian Xiuyu, Garg Varun, Celebier Mustafa, Liu Wei, Xu Jun, Cini Nejla, Ma Shuangcheng, Gölcü Ayşegül, Izat Nihan, Dai Zhong, Liu Xin-Yu, Huah Lim Siew, Liang Li, Bisth Shradha, Chen Lexing, Hu Yi-Chen, Hui Wong Kah, Sahin Selma, and Mittal Neeraj

Subjects
Analytical Chemistry
Abstract

Background: The development of innovative approaches in drug analysis is a challenging task for medicine, pharmacy, and engineering sciences. For instance, the requirement of proper dosage forms in releasing active ingredients is crucial. It is essential to analyze drugs in biological liquids for early diagnosis and treatment purposes. Drug analysis is also of great importance to control the quality of pharmaceutical products, test their efficacy, and develop novel drug formulation. The present review is aimed to highlight the most recent spectrophotometric approaches applied to analyze various classes of drugs in biological media and/or dosage forms. Methods: Direct and derivative UV/UV-Vis spectrophotometry and a combination of various techniques with spectrophotometry, such as injection analysis and chemometrics, have most widely been applied in the analysis of dosage forms. In addition, emerging technologies, such as UV imaging allows to obtain the distribution of drug concentration in time-resolved 2D images based on UV light absorption, utilization of nanotechnology, self-assembled nanomaterials, and aptamer-based nanoparticles have gained interests to investigate drug assays and to quantify the proper drug release. Results: Due to their high versatility, ease of application, low cost, and fast response, spectrophotometric methods are one of the most preferable methods providing high accuracy and precision with a wide linear range in drug analysis. Conclusion: Selected examples demonstrating the applicability of spectrophotometric methods in pharmaceutical assays in this review might contribute to the overall importance of the analytical test used in modern pharmaceutical analysis.

Published
2021

12. Bioanalytical Method Validation of an RP-HPLC Method for Determination of Rifampicin in Liver Perfusion Studies

Author

Vijakumaran Ubashini, Kouhsari Ebrahim, Mazumder Rupa, F. Al Marjania Mohammed, Azarkan Mohamed, Bisth Shradha, Kaplan Ozan, Kumar Das Sumon, Liu Jiang, Gee Jun Tye, Abdul Hamid Zariyantey, Habib Jibona Rayhan, Chen Lexing, Calvo Esposito Rafaèle, Nordin Fazlina, Marta González Mariana, Bellal Hossain, H. Authman Sawsan, Priya S. Sathya, Jiang Zhounan, Mohapatra Hitesh, Abdullah Maha, Celebier Mustafa, Li Shiying, Al-Mamun Bulbul Abdullah, Gan Xia, Roy Tonmoy, Cai Shaohui, M.K. Sandhya, Izat Nihan, Xu Jun, Eugenia Errasti María, Kumar Rath Amiya, Sahin Selma, Avijit Saha Md., S. Ali Fatima, and Padhi Swarupanjali

Subjects
Bioanalysis, Liver perfusion, Chromatography, Chemistry, Biophysics, medicine, Pharmaceutical Science, Molecular Medicine, Biochemistry, Rifampicin, medicine.drug
Abstract

Background: The number of validated quantification methods for rifampicin, a prototypical Oatp inhibitor, in biological rat samples was limited. Objective: This study was conducted to validate a modified reversed-phase liquid chromatographic method for the determination of rifampicin in rat liver tissue according to the current ICH M10 Bioanalytical Method Validation Draft Guideline (2019) for application to samples of in situ rat liver perfusion studies. Methods: Liver tissue samples were obtained from recirculatory in situ rat liver perfusion studies. The analysis was performed on a C18 column with a mobile phase composed of 0.05 M phosphate buffer (pH 4.58): acetonitrile (55:45, v/v). The assay was validated for selectivity, calibration curve and range, matrix effect, carry-over, accuracy and precision, reinjection reproducibility, and stability. Results: he method was considered selective and stable, without having carry-over and matrix effects. The calibration curve was linear (R2: 0.9983) within the calibration range (0.5-60 ppm). Accuracy and precision values fulfilled the required limits. Liver concentrations of rifampicin in liver tissue, obtained after 60 min perfusion with 10 μM and 50 μM of rifampicin, were 45.1 ± 11.2 and 313.4 ± 84.4 μM, respectively. Conclusion: The bioanalytical method validation was completed and the method was successfully applied for the determination of rifampicin in rat liver tissue.

Published
2021

13. UPLC-Q-TOF/MS based Untargeted Metabolite and Lipid Analysis on Premature Ovarian Insufficiency Plasma Samples

Author

Bedir Fındık Rahime, Kaplan Ozan, Kuru Pekcan Meryem, Celebier Mustafa, and Taşcı Yasemin

Subjects
chemistry.chemical_compound, Chromatography, Plasma samples, chemistry, Metabolite, Biophysics, Pharmaceutical Science, Molecular Medicine, Premature ovarian insufficiency, Biochemistry, Uplc q tof ms
Abstract

Background: Metabolomics is one of the main areas to understand cellular process at molecular level by analyzing metabolites. In recent years metabolomics has emerged as a key tool to understand molecular basis of diseases, to find diagnostic and prognostic biomarkers and develop new treatment opportunities and drug molecules. Objective: In this study, untargeted metabolite and lipid analysis were performed to identify potential biomarkers on premature ovarian insufficiency plasma samples. 43 POI subject plasma samples were compared with 32 healthy subject plasma samples. Methods: Plasma samples were pooled and extracted using chloroform:methanol:water (3:3:1 v/v/v) mixture. Agilent 6530 LC/MS Q-TOF instrument equipped with ESI source was used for analysis. A C18 column (Agilent Zorbax 1.8 μM, 50 x 2.1 mm) was used for separation of the metabolites and lipids. XCMS, an “R software” based freeware program, was used for peak picking, grouping and comparing the findings. Isotopologue Parameter Optimization (IPO) software was used to optimize XCMS parameters. The analytical methodology and data mining process were validated according to the literature. Results: 83 metabolite peaks and 213 lipid peaks were found to be in semi-quantitatively and statistically different (fold change >1.5, p Conclusion: According to the results, two groups were successfully separated through principal component analysis. Among the peaks, phenyl alanine, decanoyl-L-carnitine, 1-palmitoyl lysophosphatidylcholine and PC(O-16:0/2:0) were identified through auto MS/MS and matched with human metabolome database and proposed as plasma biomarker for POI and monitoring the patients in treatment period.

Published
2021

28. Discovery of Michael acceptor containing 1,4-dihydropyridines as first covalent inhibitors of L-/T-type calcium channels

Author

Aygün Cevher, Hande, primary, Schaller, David, additional, Gandini, Maria A., additional, Kaplan, Ozan, additional, Gambeta, Eder, additional, Zhang, Fang Xiong, additional, Çelebier, Mustafa, additional, Tahir, Muhammad Nawaz, additional, Zamponi, Gerald W., additional, Wolber, Gerhard, additional, and Gündüz, Miyase Gözde, additional

Published
2019
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30. Analytical method development on liquid chromatography mass spectrometry for metabolom analyze at differential diagnosis of ascites

Author

Kaplan, Ozan, Çelebier, Mustafa, Analitik Kimya, and Analitik Kimya Anabilim Dalı

Subjects
sıvı kromatografisi, Mass spectrometry, Ascitic fluid, Kimya, Chemistry, Chromatography-liquid, Metabolomik, Mass spectroscopy, Metabolism, Pharmacy and Pharmacology, Metabolomics, assit, Eczacılık ve Farmakoloji, kütle spektrometrisi
Abstract

Pathological fluid collected in the peritoneal cavity is called ascitic fluid. The concept of the differential diagnosis of ascites is process of diagnosing the disease that causes ascites formation. In this thesis, metabolomic studies were performed by liquid chromatography / mass spectrometry (LC/MS Q-TOF) between non malignant ascitic samples (group C) and malignant ascitic samples (group T). Study text consist of three main experimental parts: analytical method development, metabolite profiling and targeted metabolomics. In the method development step, two different sample preparation methods, ultrafiltration and methanol precipitation, two different chromatography columns, HILIC and C18 columns, two different MS modes, positive and negative MS modes, were tried and compared. Ultrafiltration technique, HILIC column and positive mode MS methods were determined as the method giving the maximum number of peaks and study was continued with this method. Metabolite profiling studies were carried out with the developed method and between two groups 141 peaks were found as minimum two times differentiating. Six of these peaks were identified in targeted metabolomic studies and chemical structures were characterized. ÖZET vii ABSTRACT viii SİMGELER ve KISALTMALAR xiii ŞEKİLLER xiv TABLOLAR xviii 1. GİRİŞ 1 2. GENEL BİLGİLER 5 2.1. Metabolit, Metabolom ve Metabolomik Kavramları 5 2.2. Metabolomik Çalışmaların Tarihsel Gelişimi 6 2.3. Metabolomik Çalışmalar ve Uygulamaları 8 2.4. Metabolomik Çalışmalarda Kullanılan Analitik Yöntemler 10 2.5. Kromatografi 11 2.5.1. Sıvı Kromatografisinin Tarihsel Gelişimi 12 2.5.2. Yüksek Basınçlı Sıvı Kromatografisi (HPLC) Sistemleri 13 2.5.3. Metabolomik Çalışmalarda Kullanılan HPLC Kolonları 14 2.5.4. Kromatografi Parametreleri 15 2.6. Kütle Spektroskopisi 16 2.6.1. Kütle Spektrometre Cihazlarının Genel Yapısı 16 2.6.2. Elektrosprey İyonlaştırıcı (ESI) 18 2.6.3. Uçuş Zamanlı Kütle Spektrometrisi (TOF) 19 2.7. Metabolomik Çalışmalar için Numune Hazırlama Yöntemleri 20 2.7.1. Ultrafiltrasyon Yöntemi 21 2.7.2. Metanolle Çöktürme Yöntemi 22 2.8. Metabolomik Çalışmalarda Yazılım ve Veri Bankası Desteği 22 2.8.1. XCMS 23 2.9. Metabolomik Çalışmalarda Deney Tasarımında Uygulanan Yaklaşımlar 25 2.9.1. Karışım Numuneleri Kullanımı 26 2.9.2. Kalite Kontrol Yaklaşımı 26 2.9.3. İç Standart Kullanımı 27 2.9.4. Dilüsyon Serisi Yöntemi 27 2.9.5. XCMS Parametrelerinin Optimizasyonu 28 2.9.6. Pik Şiddetlerinin Normalizasyonu 30 2.10. Assit Sıvısı ve Assit Ayırıcı Tanı 31 3. GEREÇ ve YÖNTEM 32 3.1. Tez Kapsamında Gerçekleştirilen Çalışmalar 32 3.1.1. Tez Çalışması Kapsamında Kullanılan Kimyasal ve Cihazlar 34 3.1.2. Assit Sıvısı Numunelerinin Toplanması ve Saklanması 35 3.1.3. Hasta ve Kontrol Grupları Oluşturulması 35 3.1.4. LC/MS Q-TOF Analizlerinde Uygulanan Metodoloji 36 3.2. Yöntem Geliştirme Çalışmaları 38 3.2.1. Karışım Numuneleri Hazırlanması 39 3.2.2. Metabolitlerin Ekstraksiyonu İçin Kullanılan Yöntemler 39 3.2.3. Metabolitlerin Ayrımı İçin Kullanılan Kolon Denemeleri 40 3.2.4. Pozitif ve Negatif Mod Denemeleri 41 3.3. Metabolit Profilleme Çalışmaları 42 3.3.1. Karışım Numuneleri ve İç Standart Eklenmesi 42 3.3.2. Kalite Kontrol Numuneleri 42 3.3.3. Dilüsyon Serisi Hazırlama 43 3.4. Veri Değerlendirme Çalışmaları 43 3.4.1. Ham Data Dosyalarının XCMS’e Uygun Olarak Dönüştürülmesi 43 3.4.2. XCMS Programının Kurulumu 44 3.4.3. XCMS Parametrelerinin Optimizasyonu 44 3.4.4. XCMS Analizleri 44 3.4.5. Veri Değerlendirilmesinde Kullanılan Yaklaşımlar 45 3.6. Sistem Uygunluk Testi 46 3.7. Validasyon Çalışmaları 46 3.7.1. Özgünlük 46 3.7.2. Doğruluk 46 3.7.3. Kesinlik 46 3.7.4. Doğrusallık 47 3.8. Hedeflenmiş Metabolomik Çalışmaları 47 4. BULGULAR 48 4.1. Yöntem Geliştirme Basamağına Ait Bulgulara Genel Bakış 48 4.1.1. Numune Hazırlama Basmağına Ait Bulgular 57 4.1.2. Farklı Kolon Denemelerine Ait Bulgular 57 4.1.3. Pozitif ve Negatif MS Modlarına Ait Bulgular 57 4.2. Metabolit Profilleme Basamağına Ait Bulgular 58 4.2.1. XCMS Optimizasyonuna Ait Bulgular 58 4.2.2. Regresyon Analizine Ait Bulgular 59 4.2.3. Kalite Kontrol Numunelerine Ait Bulgular 60 4.2.4. İç Standart Sonuçlarına Ait Bulgular 60 4.2.5. Metabolit Profillemede Veri Değerlendirme Sonuçlarına Ait Bulgular 61 4.3. Hedeflenmiş Metabolomik Çalışmaları 78 4.4. Sistem Uygunluk Çalışması 89 4.5. Validasyon Çalışmaları 89 4.5.1. Özgünlük 89 4.5.2. Doğruluk 90 4.5.3. Kesinlik 91 4.5.4. Doğrusallık 92 5. TARTIŞMA VE SONUÇ 97 5.1. Yöntem Geliştirme Çalışmaları 97 5.2. Metabolit Profilleme Çalışmaları 99 5.3. Hedeflenmiş Metabolomik Çalışmaları 102 5.3.1. Metabolomik Yolak İncelemeleri 102 5.3.2. Kreatinin 102 5.3.3. DL-Fenilalanin 104 5.3.4. Betain 105 5.3.5. L-Histidin 1055 5.3.6. L-Arginin 107 5.3.7. Oksindol 108 5.4. Validasyon Çalışmaları 109 5.4.1. Özgünlük 109 5.4.2. Doğruluk 109 5.4.3. Kesinlik 110 5.4.4. Doğrusallık 110 6. SONUÇ ve ÖNERİLER 111 7. KAYNAKLAR 113 8. EKLER 125 Ek 1. Etik Kurul Onay Sayfası Ek 2. XCMS kurulumu için kullanılan kod. Ek 3. IPO yazılımı için kullanılan kod. Ek 4. IPO optimizasyon kodu. Ek 5. Kullanılan XCMS kodu. ÖZGEÇMİŞ Peritoneal boşluk içinde toplanan patolojik sıvıya assit sıvısı denilmektedir. Assit ayırıcı tanı kavramı, bu sıvıdan yola çıkarak assit oluşumuna sebep olan hastalığa tanı koyma işlemidir. Bu tez çalışması kapsamında malign nedene bağlı olmadan assit oluşumu gösteren assit numuneleri (C grubu) ile, malign nedene bağlı olarak assit oluşumu gösteren assit numuneleri arasında (T grubu) sıvı kromatografisi kütle spektrometrisi (LC/MS Q-TOF) yöntemi ile metabolomik çalışmalar yapılarak metabolom düzeyinde assit ayırıcı tanı için kullanılabilecek biyobelirteçler bulunmaya çalışılmıştır. Çalışmalar, analitik yöntem geliştirme, metabolit profilleme ve hedeflenmiş metabolomik olmak üzere üç ana deneysel kısımdan oluşmaktadır. Yöntem geliştirme basamağında ultrafiltrasyon ve metanolle çöktürme olmak üzere iki farklı numune hazırlama yöntemi, HILIC ve C18 kolonlar ile ayırım olmak üzere iki farklı ayırım metodu, pozitif ve negatif MS modları olmak üzere iki farklı MS modu denenmiştir. Ultrafiltrasyon tekniği, HILIC kolon ve pozitif mod MS yöntemleri en fazla pik sayısını veren yöntem olarak belirlenmiş ve çalışma bu yöntemle devam ettirilmiştir. Geliştirilen yöntemle metabolit profilleme çalışmaları yapılmış ve iki grup arasında 141 adet miktarı en az iki kat farklılaşan pik bulunmuştur. Bu piklerden 6 tanesi hedeflenmiş metabolomik çalışmalarında tanımlanmış ve kimyasal yapıları belirlenmiştir.

Published
2017

32. Liquid-liquid extraction and ultrafiltration based sample preparation technique for Q-TOF LC/MS analysis of nonpolar metabolites in human plasma samples.

Author

KOÇAK, Engin, KAPLAN, Ozan, and ÇELEBİER, Mustafa

Subjects
*LIQUID-liquid extraction, *METABOLITES, *CHEMICAL sample preparation, *EXTRACTION techniques, *METABOLITE analysis, *SAMPLING (Process), *ULTRAFILTRATION, *GRADIENT elution (Chromatography)
Abstract

Metabolomics is one of the main areas to understand cellular process at molecular level by analyzing metabolites. In recent years, metabolomics has been emerged as key tool to understand molecular basis of disease, find diagnostic and prognostic biomarkers, and develop new treatment opportunities. One of the most important challenge for metabolomics analysis is sample complexity due to wide concentration dynamics. In untargeted metabolomics studies for human plasma samples, generally there is no pre-fractioning method for metabolites prior to LC/MS analysis. This situation causes problem for analysis of some specific metabolites belonging to different pathways in such a complex system. In this study, it was offered liquid-liquid extraction and ultrafiltration-based sample preparation technique for fractioning of non-polar metabolites. Human plasma metabolites were extracted with a well-known cosolvent system (methanol/water/chloroform) and separated according to their polarity in aqueous and organic phases. Ultrafiltration process was performed for both phases to clean-up the sample. Solvents were evaporated and the remaining parts were dissolved in an organic solvent, acetonitrile, to obtain the non-polar metabolite mixtures. Samples were analyzed using Q-TOF LC/MS system for metabolite profiling. Metabolites were separated in a C18 (Agilent Zorbax C18 1.8 μM, 50 x 2.1 mm) column at 0.200 ml min-1 flow rate. Water and acetonitrile mixture including 0.1% formic acid was used as the mobile phase in a 25 min gradient elution system. In the aqueous phase, 249 peaks were found and 60 peaks were obtained in the organic phase. 14 peaks were common in both phases. Results showed that co- solvent system could be used for pre-fractioning of metabolites and reduce complexity of human plasma for metabolite profiling. [ABSTRACT FROM AUTHOR]

Published
2020
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34. UPLC-Q-TOF/MS based Untargeted Metabolite and Lipid Analysis on Premature Ovarian Insufficiency Plasma Samples

Author

TaŦ#159;cı, Yasemin, Fındık, Rahime B., Pekcan, Meryem Kuru, Kaplan, Ozan, and Celebier, Mustafa

Abstract

Background: Metabolomics is one of the main areas to understand cellular process at molecular level by analyzing metabolites. In recent years metabolomics has emerged as a key tool to understand molecular basis of diseases, to find diagnostic and prognostic biomarkers and develop new treatment opportunities and drug molecules. Objective: In this study, untargeted metabolite and lipid analysis were performed to identify potential biomarkers on premature ovarian insufficiency plasma samples. 43 POI subject plasma samples were compared with 32 healthy subject plasma samples. Methods: Plasma samples were pooled and extracted using chloroform:methanol:water (3:3:1 v/v/v) mixture. Agilent 6530 LC/MS Q-TOF instrument equipped with ESI source was used for analysis. A C18 column (Agilent Zorbax 1.8 μM, 50 x 2.1 mm) was used for separation of the metabolites and lipids. XCMS, an “R software” based freeware program, was used for peak picking, grouping and comparing the findings. Isotopologue Parameter Optimization (IPO) software was used to optimize XCMS parameters. The analytical methodology and data mining process were validated according to the literature. Results: 83 metabolite peaks and 213 lipid peaks were found to be in semi-quantitatively and statistically different (fold change >1.5, p <0.05) between the POI plasma samples and control subjects. Conclusion: According to the results, two groups were successfully separated through principal component analysis. Among the peaks, phenyl alanine, decanoyl-L-carnitine, 1-palmitoyl lysophosphatidylcholine and PC(O-16:0/2:0) were identified through auto MS/MS and matched with human metabolome database and proposed as plasma biomarker for POI and monitoring the patients in treatment period.

Published
2021
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35. Yiv Uygulamasının Düz Levha Üzerinde Sürtünme Direncine Olan Etkisinin İncelenmesi

Author

Kaplan, Ozan, Ünal, Uğur Oral, Gemi İnşaatı ve Gemi Makinaları Mühendisliği, Naval Architecture and Marine Engineering, and Gemi İnşaatı ve Gemi Makineleri Mühendisliği Ana Bilim Dalı

Subjects
Bilim ve Teknoloji, Riblet Application, Gemi Mühendisliği, Had, Yiv Uygulaması, Science and Technology, Cfd, Marine Engineering
Abstract

Tez (Yüksek Lisans) -- İstanbul Teknik Üniversitesi, Fen Bilimleri Enstitüsü, 2016, Thesis (M.Sc.) -- İstanbul Technical University, Instıtute of Science and Technology, 2016, Direnç kuvveti, birçok alanda, özellikle de mühendislik uygulamalarında önemli bir yere sahiptir. Yüzen cisimlerdeki toplam direnci, en temel olarak, viskoz basınç direnci, yüzey sürtünme direnci ve dalga direnci bileşenleri oluştururken, batmış cisimler üzerinde dalga direnci mevcut değildir. Her iki durumda da yüzey sürtünme direncinin toplam dirence katkısı oldukça büyüktür. Bu sebeple, literatürde yüzey sürtünme direncinin azaltılması ile ilgili aktif ve pasif yöntemlere sıkça rastlanmaktadır. Yüzeye ince yivler açılması vasıtasıyla sürtünme direncinin azaltılmasının etkin pasif yöntemler arasında gösterilmesi mümkündür. Bu çalışmada, temel yiv ve geometrileri ele alınarak düz levha üzerine uygulanan farklı yiv konfigürasyonları sistematik olarak hesaplamalı yöntemlerle incelenmiştir. Bu konfigürasyonlar arasından literatürde en fazla incelenen V, U, bıçak ağzı ve ikizkenar yamuk şeklindeki yiv uygulamaları ele alınmıştır. Yapılan çalışma Hesaplamalı Akışkanlar Dinamiği (HAD) yöntemi ile gerçekleştirilmiştir. Aynı zamanda, analizlerin gerçekleştirildiği sonlu hacim metodundan, hız basınç ayrıklaştırılmasının yapıldığı SIMPLE yöntemi ve türbülans modeli olarak seçilen SST k-ω modelinden detaylı olarak bahsedilmiştir. Çalışmadaki asıl amaç yüzeye kontrollü yiv uygulaması ile sürtünme direncinin azaltılmasıdır. Bunun için yiv ile ilgili temel akış parametreleri ele alınarak sistematik bir Hesaplamalı Akışkanlar Dinamiği (HAD) çalışması yapılmış, düz levha ile yapılan karşılaştırma sonucunda en etkin yiv uygulamasının belirlenmesi amaçlanmıştır. Literatürde, Walsh (1982), Bechert ve diğ. (1997) ve Choi (1989)’nin yapmış olduğu deneysel çalışmalarda etkili yiv konfigürasyonlarında s+ değer aralığının yaklaşık 5 ile 30 arasında olduğu tespit edilmiştir. Buna göre uygun hız değerinin 5 m/s civarında olduğu belirlenmiş ve hesaplamalı çalışmalarda sırasıyla 3, 5 ve 8 m/s serbest akım hızları kullanılmıştır. Belirlenen bu hızlarda, ilk olarak h/s oran parametresi esas alınarak dört farklı yiv uygulaması ile düz levhaya ait direnç kuvveti değerleri arasında karşılaştırma yapılmıştır. İlk olarak düz levha üzerinde farklı serbest akım hızlarında (3, 5 ve 8 m/s) direnç kuvveti (RF), toplam sürtünme direnç katsayısı (CF) ve yerel sürtünme direnç katsayısı (Cf) parametrelerine ait değerler incelenmiştir. CF değeri, Karman-Schoenherr’e göre incelenmiş ve bu inceleme sonucunda yiv uygulamalarına ait CF değerleriyle yapılacak olan karşılaştırmada kullanılacak referans CF değeri belirlenmiştir. Cf değeri için ise, levha üzerinde x yönünde belirlenen üç farklı noktada (x=0.65, 0.70 ve 0.90) Clauser’e göre yer değiştirme kalınlığına bağlı olarak ve Coles’a göre momentum kalınlığına bağlı olarak incelemeler yapılmış ve bu inceleme sonucunda, hesaplamalı çalışmadan elde edilen Cf değerlerinin ele alınan Reδ1 aralığında Clauser eğrisi ile yaklaşık olarak ± % 1 duyarlılıkla uyum sağladığı, ele alınan Reϴ aralığında ise Coles eğrisi ile yaklaşık olarak ± % 3 duyarlılıkla uyum sağladığı görülmüştür. Bundan sonraki adımda, pasif direnç azaltıcı yöntemlerden yiv uygulamasına ait inceleme yapılacak parametreler belirlenmiştir (hız değeri, yiv yüksekliği (h), yiv yüksekliğinin yiv aralığına oranı (h/s) ve boyutsuz parametre olan s+). Belirlenen bu parametreler çerçevesinde ilk olarak h/s=0.5’te üç farklı serbest akım hızında gerçekleştirilen hesaplamalı çalışma sonucunda elde edilen RF değerleri ile aynı hızlarda düz levhaya ait RF değerleri incelendiğinde yaklaşık olarak en fazla direnç düşüşünün V şeklindeki yiv uygulamasında, en az ise bıçak ağzı yiv uygulamasında sağlandığı tespit edilmiştir. Aynı hesaplamalı çalışma h/s=1 için de gerçekleştirilmiş ve bu değerde de yaklaşık olarak en fazla direnç düşüşünün V şeklindeki yiv uygulamasında, en az ise bıçak ağzı yiv uygulamasında sağlandığı görülmüştür. Yapılan bu tespitlerden sonra, bundan sonraki adımlarda V şeklindeki yiv uygulaması üzerinden yapılan incelemeler detaylandırılmıştır. Çizelgeler halinde verilmiş olan V şeklindeki yiv uygulamasına ait farklı serbest akım hızlarında ve farklı h/s oranlarında gerçekleştirilen hesaplamalı çalışma sonucunda elde edilen RF değerleri ile düz levhaya ait RF değerleri karşılaştırılmıştır. Bu karşılaştırma sonucunda, aynı h/s oranında, 3, 5 ve 8 m/s’deki yiv uygulamalarına ait direnç kuvveti (RF) değerleri ile aynı hızlarda düz levha üzerindeki direnç kuvveti (RF) değerlerinin karşılaştırılması sonucunda yaklaşık olarak en fazla direnç kuvveti düşüşü V şeklindeki yiv uygulamasında, en az direnç kuvveti düşüşü ise bıçak ağzı şeklindeki yiv uygulamasında görülmüştür. Aynı h/s ve hız değerlerine ait veriler incelendiğinde ise s+ değerinin artması ile yaklaşık olarak direnç kuvveti düşüşünün de arttığı tespit edilmiştir. Farklı h ve s değerinde, fakat aynı h/s oranına sahip (Örneğin, 1- h=0.01875 ve s=0.0375, h/s=0.5 2- h=0.05 ve s=0.1, h/s=0.5) ve aynı hızlardaki verilerin incelenmesi neticesinde, s+ değerinin artması ile direnç kuvveti düşüşünün azaldığı görülmüştür. Aynı h ve s değerlerine sahip, farklı serbest akım hızlarındaki yiv uygulamalarında ise (Örneğin, 1- h=0.1 ve s=0.1, hız=3 m/s, 2- h=0.1 ve s=0.1, hız 5 m/s) hız değerinin ve buna bağlı olarak s+ değerinin artması ile direnç kuvveti düşüş değerinin arttığı gözlemlenmiştir. Düz levha ile V ve BA yiv uygulamalarına ait girdaplılık ve türbülans kinetik enerjilerine ait dağılımların incelenmesi neticesinde, düz levha ile V ve BA yiv uygulamaları arasında ciddi farklılıkların olduğu gözlemlenmiştir. Düz levhada duvar cidarındaki girdaplılık dağılımının yiv uygulaması ile duvar cidarından uzaklaştığı ve yiv tepe noktalarında yoğunlaştığı görülmüştür. V ve BA yiv uygulamalarının tepe noktalarındaki girdaplılık dağılımına ait karşılaştırmada ise, BA yivdeki dağılımın V yivdeki dağılıma göre daha fazla olduğu tespit edilmiştir. Düz levha ile V ve BA yive ait türbülans kinetik enerjileri dağılımına ait karşılaştırma neticesinde, türbülans kinetik enerjinin yiv uygulamalarında düz levhaya göre daha az seviyede olduğu tespit edilmiştir. Özellikle V yivde türbülans kinetik enerjinin en az seviyeye indirgendiği görülmüştür., Resistance force, in many areas especially in engineering applications, has an important place. The total resistance of floating bodies, the most basic, involves in the components of the viscous pressure resistance, skin friction resistance and wave resistance, but on the sinking bodies the wave resistance is not involved. In both cases, the contribution to the total resistance of the skin friction resistance is quite large. Therefore, it is common to the active and passive method for reducing the skin friction resistance in the literature. Investigating the reduction of skin friction by opening thin riblets through the effective passive methods are possible. In this study, dealing with the riblets and their geometries different riblet configurations which are applied on the flat plate are systematically studied by computational methods. Through these configurations the riblet applications which are the most studied in the literature are V, U, blade and trapezoidal riblets. Furthermore, the boundary layer thickness, the displacement thickness and the momentum thickness are explained because of the investigation of the total friction coefficient (CF) on the flat plate. After that, the explanations for the V, U, blade and trapezoidal riblet applications are given. There are a lot of experimental studies on the riblet applications: V, U, blade and trapezoidal which are the most common. In all these experimental studies the drag reduction is identified. The highest drag reduction percentage is approximately % 10 on blade riblet application and on V riblet application the drag reduction percentage is approximately % 6-8. The studies were carried out with the method of Computational Fluid Dynamics (CFD). Theoretical background on Computational Fluid Dynamics was given with its historical progress. Besides, detailed information is given about incompressible Reynolds Averaged Navier Stokes (RANS) based two equation eddy viscosity SST (Shear Stress Transport) k-ω turbulence model and pressure velocity relation algorithm for steady flow is taken SIMPLE (Semi-Implicit Method for Pressure--Linked Equations) algorithm which denotes pressure-velocity relation for steady flows that are chosen by this thesis. Moreover, Law of the Wall is briefly explained. In this study, dimensionless distance from the wall y+ values is attempted lower than 5. Since, the flow separation is investigated properly with y+, Yüksek Lisans, M.Sc.

Published
2016

36. DENİZ SEKTÖRÜNDE KULLANILAN KOMPOZİT MALZEMELERİN MEKANİK ÖZELLİKLERİNİN BELİRLENMESİ İÇİN BASİT BİR DENEY DÜZENEĞİ

Author

SEZEN, Savaş, DUMAN, Süleyman, KAPLAN, Ozan, ÜNSAN, Yalçın, and KORKUT, Emin

Subjects
Kompozit,Cam Elyaf,Çekme Deney Cihazı Tasarımı,Üretim Tekniği,Belirsizlik Analizi
Abstract

Bu çalışmada, kompozit malzeme çeşitleri ve üretim aşamalarından bahsedilerek uygun deney düzeneği tasarımları araştırılarak en uygun sistemin seçiminin yapılması anlatılmıştır. Farklı örgü ve gramajlara sahip cam elyaf malzemesinden elle yatırma tekniği ile deney numunelerinin nasıl üretildiği üzerinde durulmuştur. Ayrıca mekanik özelliklerin belirlenmesi için deneyin yapılabileceği çekme deney düzeneği imal edilerek kompozit numunelerin kopma gerilmeleri ölçülmüştür. Bu deney düzeneği çoğu işletmede ucuz ve kolay kurulabilecek bir sistem amaçlanarak geliştirilmiştir

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