Publications

@article{pmid40327944,

title = {Development of HPLC methodology for quantification of naltrexone and 6β-naltrexol in human plasma and its potential in alcohol use disorder treatment monitoring},

author = {Ceren H Bozmaoglu and Kenan Can Tok and Mustafa Danisman and H Sinan Suzen and Mehmet Gumustas},

doi = {10.1016/j.jpba.2025.116944},

issn = {1873-264X},

year  = {2025},

date = {2025-09-01},

journal = {J Pharm Biomed Anal},

volume = {263},

pages = {116944},

abstract = {Alcohol use disorder remains a significant public health challenge, with pharmacotherapy playing a critical role in treatment. Given the low rates of compliance and persistence in alcohol use disorder pharmacotherapy, the development of robust monitoring methods is essential to improve therapeutic outcomes. This study introduces a novel, environmentally friendly, high-performance liquid chromatography method for simultaneously quantifying naltrexone and its primary metabolite, 6β-naltrexol, in plasma while also reducing sample preparation time and simplifying extraction steps. Notably, it is the first high-sensitivity method in the literature that employs a UV detector, offering a cost-effective and accessible alternative to conventional detection techniques. Chromatographic separation was performed using a Kinetex EVO C18 (150 × 4.6 mm i.d.; 5 µm) column with a mobile phase composed of methanol and 0.1 % ortho-phosphoric acid in water (containing 0.1 % TEA) (20:80, v/v) at a flow rate of 0.4 mL/min. The column oven was set to 15°C, and the detection wavelength was 204 nm. The developed method was validated for selectivity, linearity, limit of detection, limit of quantification, precision, and accuracy in accordance with the guidelines set by the U.S. Food and Drug Administration. The validated method was successfully applied for the simultaneous determination and quantification of naltrexone and 6β-naltrexol in patients diagnosed with alcohol use disorder according to Diagnostic and Statistical Manual of Mental Disorders-5, who are undergoing treatment with naltrexone. This research provides a significant contribution to analytical research and drug monitoring. It enhances efficiency and sustainability in chromatographic analysis.},

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@article{pmid40068233,

title = {Development of a sample preparation and analysis method for therapeutic monitoring of diazepam and major metabolite in alcohol withdrawal syndrome treatment},

author = {Kenan Can Tok and Selin Ozkan-Kotiloglu and Ceren H Bozmaoglu and Mustafa Danisman and Inci Ozgur-Ilhan and Dilek Kaya-Akyuzlu and H Sinan Suzen and Mehmet Gumustas},

doi = {10.1016/j.jpba.2025.116805},

issn = {1873-264X},

year  = {2025},

date = {2025-08-01},

journal = {J Pharm Biomed Anal},

volume = {260},

pages = {116805},

abstract = {Diazepam, a widely prescribed benzodiazepine, is frequently used for the management of alcohol withdrawal syndrome, anxiety, seizures, and muscle spasms. Its monitoring is critical due to its potential for abuse and the therapeutic importance of its metabolite nordiazepam. A sustainable and environmentally friendly high-performance liquid chromatography method was developed and validated for the quantification of diazepam and its active metabolite nordiazepam in human plasma samples. The chromatographic analysis was conducted on an HPLC system equipped with a UV detector. Separation was achieved using a Kinetex F5 column (150 ×4.6 mm, 5 µm). The mobile phase consisted of acetonitrile and phosphate buffer adjusted to pH 4.3 (30:70, v/v), delivered in isocratic mode at a flow rate of 1.0 mL/min, with the pH adjusted to optimize resolution. The method demonstrated excellent sensitivity, reproducibility, and linearity for both compounds, highlighting its applicability for drug monitoring and toxicological studies. Moreover, the environmentally conscious selection of materials and conditions underscores the method's compliance with green analytical chemistry principles. Both analytes were successfully detected and quantified in all fifty-three patients under the treatment of alcohol withdrawal syndrome. The measured concentrations of diazepam (0.23-1.4 µg/mL) and its metabolite nordiazepam (0.22-3.78 µg/mL) displayed considerable variability among individuals.},

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pubstate = {published},

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}

@article{pmid40660855,

title = {Emetine: Advances in Pharmacology, Toxicology, and Chromatographic Approaches},

author = {Weldejeworgis Gebrehiwot and Kenan Can Tok and Jamilah S Alkhashi and Oladapo Bakare and Mehmet Gumustas},

doi = {10.1080/10408347.2025.2529458},

issn = {1547-6510},

year  = {2025},

date = {2025-07-01},

journal = {Crit Rev Anal Chem},

pages = {1--14},

abstract = {Emetine, derived from Psychotria ipecacuanha, is a tetrahydroisoquinoline alkaloid known for its diverse pharmacological activities, making it a versatile candidate for therapeutic applications. It has demonstrated efficacy against various conditions, including cancer and other viral infections by disrupting viral protein synthesis and assembly, particularly against influenza and Ebola viruses. Despite its therapeutic potential, concerns about cardiotoxicity have limited its clinical use, prompting exploration into safer administration routes and novel formulations. Emetine's anti-cancer properties involve inhibiting the Wnt/β-catenin pathway in breast cancer cells and showing promise in treating pulmonary arterial hypertension by suppressing pulmonary artery smooth muscle cell proliferation. Liquid chromatography plays a pivotal role in characterizing and quantifying emetine and related compounds, crucial for drug development and quality control by enhancing detection sensitivity and specificity in samples. Addressing concerns over emetine's toxicity novel approaches like pH-dependent prodrugs and targeted delivery systems are under development to improve safety and efficacy profiles. This review consolidates current knowledge on emetine's pharmacology and the essential role of analytical methodologies in its study and development. It focuses on recent advancements from 1979 to 2024 in liquid chromatography analysis and applications of emetine and its derivatives in drug research, health sciences, as well as forensic purposes.},

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@article{pmid39761923,

title = {The effects of UGT1A4 and ABCB1 polymorphisms on clozapine and N- desmethyl clozapine plasma levels in Turkish schizophrenia patients},

author = {Fezile Ozdemir and Merve Demirbugen Oz and Kenan Can Tok and Emrah Dural and Yagmur Kır and Mehmet Gumustas and Bora Baskak and H Sinan Suzen},

doi = {10.1016/j.taap.2024.117219},

issn = {1096-0333},

year  = {2025},

date = {2025-02-01},

journal = {Toxicol Appl Pharmacol},

volume = {495},

pages = {117219},

abstract = {Clozapine (CLZ) is an antipsychotic which is particularly used in treatment resistant schizophrenia patients who do not respond to other agents. It is preferred because it reduces suicidal behaviours and attempts, reducing aggression and violent behaviour. The aim of the study is to evaluate the effects of ABCB1 rs1045642 and UGT1A4 rs2011425 polymorphisms on CLZ and its major metabolite N- desmethly clozapine (DCLZ) plasma concentrations in patients with schizophrenia. A total 109 of Turkish patients with schizophrenia on continually administered CLZ monotherapy were included. The plasma concentrations of CLZ and DCLZ were measured using an HPLC after liquid-liquid extraction while, transporter gene ABCB1 and phase two enzyme UGT1A4 polymorphisms were identified using PCR- RFLP method. Results showed that UGT1A4*3 polymorphism has statistically significant effects on CLZ C/D and DCLZ C/D levels in patients with sub/supra therapeutic levels while ABCB1 C3435T polymorphism has a significant effect on CLZ/DCLZ ratio among patients who have subtherapeutic levels. This study indicates the influence of genetic differences on plasma levels and highlights the importance of pharmacogenetic studies in clinic. Using the obtained results as pharmacogenetic biomarkers will help clinicians provide effective treatment in individual patients and reduce the undesirable side effects.},

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@article{pmid39258750,

title = {A Novel Bioprotective Strain of  F2-Physiological, Genetical, and Antimicrobial Characterization},

author = {Evrim Gunes Altuntas and Asena Aslihan Celık and Busra Sevım and Kenan Can Tok and Mehmet Gumustas and Hatice Mergen and Vijay K Juneja},

doi = {10.1089/fpd.2024.0005},

issn = {1556-7125},

year  = {2024},

date = {2024-09-01},

journal = {Foodborne Pathog Dis},

abstract = { is a member of lactic acid bacteria that improves the quality of fermented foods while also having a positive impact on human health. In this study,  F2 was studied for characteristics such as biochemical and genetic identification, metabolite production, antimicrobial activity, and plasmid content. This strain exerts antimicrobial activity against some Gram-positive and Gram-negative pathogens (, , , and ) with inhibition zone diameters ranging between 17.0 and 29.0 mm; it can ferment glucose, arabinose, galactose, lactose, and demonstrated the ability to grow at high temperature (50°C). Another physiological specification of the strain was the morphology of the isolate in selective medium, the de Man, Rogosa, Sharpe medium (MRS medium containing triphenyl tetrazolium chloride), which exhibits a chromogenic colony (characterized as purple colonies) on the modified-MRS (mMRS) medium. Metabolites such as lactic acid and diacetyl production of the strain F2 were also investigated using chromatography and found to be 10.07 and 0.05 µg/mL, respectively. The peptides of the isolate's cell-free supernatant were determined to be ∼80 kDa, and finally, the plasmid isolated from the strain F2 was identified as  strain KLDS1.0386 plasmid p4, which may be responsible for some characteristic properties, such as antimicrobial peptide production of the strain.},

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}

@article{pmid38521023,

title = {Highly selective and sensitive molecularly imprinted sensors for the electrochemical assay of quercetin in methanol extracts of Rubus sanctus and Fragaria vesca},

author = {M Mesud Hurkul and Ahmet Cetinkaya and Seyda Yayla and S Irem Kaya and Fatma Budak and Kenan Can Tok and Mehmet Gumustas and Lokman Uzun and Sibel A Ozkan},

doi = {10.1016/j.talanta.2024.125883},

issn = {1873-3573},

year  = {2024},

date = {2024-06-01},

journal = {Talanta},

volume = {273},

pages = {125883},

abstract = {Quercetin (QUE) is a powerful antioxidant and one of the common phenolic compounds found in plants, vegetables, and fruits, which has shown many pharmacological activities. The complex nature of the matrix in which QUE is found and its importance and potential uses in diverse applications force the researchers to develop selective and sensitive sensors. In the present work, a novel molecularly imprinted polymer (MIP)-based electrochemical sensor was fabricated for the selective and sensitive determination of the QUE in plant extracts and food supplements. Tryptophan methacrylate (TrpMA) was chosen as the functional monomer, whereas the photopolymerization (PP) method was applied using a glassy carbon electrode (GCE). Electrochemical and morphological characterizations of the developed sensor (TrpMA@QUE/MIP-GCE) were performed using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and scanning electron microscopy (SEM). The linear range of the developed sensor was determined to be in the range of 1.0-25 pM, while the limit of detection (LOD) was calculated to be 0.235 pM. In conclusion, The TrpMA@QUE/MIP-GCE sensor might be classified as a promising platform for selective and sensitive determination of QUE not only in plant extracts but also in commercial food supplements because of its reliability, reproducibility, repeatability, stability, and fast response time.},

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pubstate = {published},

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@article{pmid36828687,

title = {Electrochemical detection of lactate produced by foodborne presumptive lactic acid bacteria},

author = {Ozum Ozoglu and Aytekin Uzunoglu and Mehmet Altay Unal and Mehmet Gumustas and Sibel Aysıl Ozkan and Mihriban Korukluoglu and Evrim Gunes Altuntas},

doi = {10.1016/j.jbiosc.2022.12.014},

issn = {1347-4421},

year  = {2023},

date = {2023-04-01},

journal = {J Biosci Bioeng},

volume = {135},

number = {4},

pages = {313--320},

abstract = {The detection of lactate is an important indicator of the freshness, stability, and storage stability of products as well as the degree of fermentation in the food industry. In addition, it can be used as a diagnostic tool in patients' healthcare since it is known that the lactate level in blood increases in some pathological conditions. Thus, the determination of lactate level plays an important role in not only the food industry but also in health fields. As a result, biosensor technologies, which are quick, cheap, and easy to use, have become important for lactate detection. In the current study, amperometric lactate biosensors based on lactate oxidase immobilization (with Nafion 5% wt) were designed and the limit of detection, linear range, and sensitivity values were determined to be 31 μM, 50-350 μM, and 0.04 μA μM cm, respectively. Then, it was used for the measurement of lactic acid that produced by six different and morphologically identified presumptive lactic acid bacteria (LAB) which are isolated from different naturally fermented cheese samples. The biosensors were then used to successfully perform lactate measurements within 3 min for each sample, even though a few of them were out of the limit of detection. Thus, electrochemical biosensors should be used as an alternative and quick solutions for the measurement of lactate metabolites rather than the traditional methods which require long working hours. This is the first study to use a biosensor to measure lactate produced by foodborne LAB in a real sample.},

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@article{pmid34601980,

title = {Chiral Sensing as a Future Challenge in Electroanalytical Chemistry: Cyclodextrin-Based Chiral Sensors},

author = {Leyla Karadurmus and Mehmet Gumustas and Nurgul K Bakirhan and Sibel A Ozkan},

doi = {10.1080/10408347.2021.1967108},

issn = {1547-6510},

year  = {2023},

date = {2023-01-01},

journal = {Crit Rev Anal Chem},

volume = {53},

number = {3},

pages = {498--519},

abstract = {Chirality is an academically exciting and interesting topic, as most active ingredients have chirality. Chiral enantiomers with the same molecular shape show different effects from each other in terms of pharmacological, pharmacokinetic, and toxicology. There are many examples of these differences that have caused dramatic, even fatal damage. For these reasons, it is of great importance to developing an effective method to achieve chiral identification and separation, and chiral separation methods are becoming increasingly important in both the pharmaceutical industry and clinical studies. Electrochemical techniques, which can provide many advantages over other classical methods, have attracted great interest in chiral recognition in recent years. In this review, extensive and critical research of the trends in chiral recognition in recent studies is explained. Especially the role of cyclodextrins derivatives in chiral analysis has been investigated and the studies related to this are explained and given in the tables. In addition, some remarks and future perspectives in the field of chiral recognition are also discussed in the concluding part.},

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tppubtype = {article}

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@article{pmid37269349,

title = {The Potential Role of  and  Genetic Variations and Lifestyle Factors on Clozapine and N-DesmethylClozapine Plasma Levels in Schizophrenia Patients},

author = {Merve Demirbugen Oz and Fezile Ozdemir and Kenan Can Tok and Emrah Dural and Yagmur Kir and Muge Ulusoy and Mehmet Gumustas and Bora Baskak and H Sinan Suzen},

doi = {10.1080/17425255.2023.2221849},

issn = {1744-7607},

year  = {2023},

date = {2023-01-01},

journal = {Expert Opin Drug Metab Toxicol},

volume = {19},

number = {5},

pages = {319--327},

abstract = {BACKGROUND: Despite its advantages over other antipsychotics, for treatment-resistant schizophrenia, clinical use of Clozapine (CLZ) is challenging by its narrow therapeutic index and potentially life-threatening dose-related adverse effects.nnRESEARCH DESIGN AND METHODS: As the potential role in CLZ metabolism is assigned to CYP1A2 enzyme and consequently Cytochrome P450 oxidoreductase (POR) their genetic variations might help to determine CLZ levels in schizophrenia patients. For this purpose, 112 schizophrenia patients receiving CLZ were included in the current study. Plasma CLZ and N-desmethylclozapine (DCLZ) levels were analyzed by using HPLC and genetic variations were identified with the PCR-RFLP method.nnRESULTS: The patients'  and  genotypes seemed to not affect plasma CLZ and DCLZ levels whereas in the subgroup analysis,  genotype significantly influenced simple and adjusted plasma CLZ and DLCZ levels concerning smoking habit and caffeine consumption.nnCONCLUSIONS: The findings of the present study highlight the importance of both genetic and non-genetic factors (smoking and caffeine consumption) for the individualization of the CLZ treatment. In addition to that, it suggests that the added utility of not only the CLZ metabolizing enzymes but also POR, which is crucial for proper CYP activity, to guide CLZ dosing might be useful for clinical decision-making.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid36215920,

title = {Separation of the enantiomers of underivatized amino acids by using serially connected dual column high-performance liquid chromatography-tandem mass spectrometry},

author = {Tuğçe Öztepe and Nermin Büşra Kale and Tuba Reçber and İpek Baysal and Samiye Yabanoğlu-Çiftçi and Mehmet Gumustas and Sedef Kır and Bezhan Chankvetadze and Emirhan Nemutlu},

doi = {10.1016/j.chroma.2022.463529},

issn = {1873-3778},

year  = {2022},

date = {2022-11-01},

journal = {J Chromatogr A},

volume = {1683},

pages = {463529},

abstract = {In this article, a serially connected dual column liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is described for the simultaneous separation and enantioseparation of proteinogenic amino acids. For this purpose, different achiral and chiral stationary phases (CSP) and mobile phase compositions have been tested. As a result of the optimization studies, the best enatioseparation for amino acids were achieved with a combination of zwitterionic and crown ether stationary phases using a gradient of two mobile phases: A (water:TFA 99.5:0.5, % v/v) and B (acetonitrile:ethanol:TFA 85:15:0.5, % v/v/v). The developed method provided simultaneous enantioseparation of all proteinogenic amino acids under this study including isomeric and isobaric ones except for proline. The method was successfully applied to human lung adenocarcinoma cells (A549) and healthy human lung epithelial cells (BEAS-2B) cultivated with d-amino acid containing cocktails in order to evaluate d-amino acids transfer rate in normal and cancer lines. Thed/l amino acid ratios were different in cancer and normal cell lines cultivated as mentioned above for aspartic acid, cysteine, methionine, phenylalanine, and serine.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid35908414,

title = {Development of salting-out extraction methodology for the determination of piroxicam from polymeric based nanocarriers and biological samples},

author = {Kenan Can Tok and Mehmet Gumustas and Ceyda Tuba Sengel-Turk and Gulin Amasya and Bilge Bayram and Ebru Arioglu-Inan},

doi = {10.1016/j.jpba.2022.114966},

issn = {1873-264X},

year  = {2022},

date = {2022-09-01},

journal = {J Pharm Biomed Anal},

volume = {219},

pages = {114966},

abstract = {The aim of the present study is to develop the polymeric nanoparticulate drug delivery systems of piroxicam and to evaluate the in-vitro characteristics such as entrapment efficiency, surface morphology, in-vitro drug release performance, etc. For this reason, a novel HPLC methodology was developed for the determination of piroxicam from its bulk form, pharmaceutical preparation, and nanoparticulate delivery systems. Furthermore, the developed formulation was applied to the rats and the biological samples (plasma, liver, heart, spleen, kidney, and lung homogenates) were analyzed by the developed HPLC method following a salting-out assisted liquid-liquid extraction strategy for the first time in the literature. A Kinetex C18 analytical column (150 mm × 4.6 mm i.d., 5 µm) was used as a stationary phase with a 0.8 mL/min flow rate of acetonitrile: phosphate buffer (40:60, v/v), the column oven was adjusted to 40 °C and detection wavelength is set to 360 nm. Developed method were validated as per selectivity, linearity, LOD, LOQ, precision, and accuracy specified in the International Council for Harmonisation guidelines. As a result of the present study, it has been shown that the analysis of piroxicam from the bulk form, pharmaceutical preparation, developed polymeric-based drug delivery system, and biological samples can be successfully performed and no interferences were observed in any matrix. The developed method was also successfully utilized to study the tissue distribution of piroxicam in rats.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid35759032,

title = {Investigation of the probiotic and metabolic potential of Fructobacillus tropaeoli and Apilactobacillus kunkeei from apiaries},

author = {Duygu Simsek and Merve Eylul Kiymaci and Kenan Can Tok and Mehmet Gumustas and Nurten Altanlar},

doi = {10.1007/s00203-022-03000-x},

issn = {1432-072X},

year  = {2022},

date = {2022-06-01},

journal = {Arch Microbiol},

volume = {204},

number = {7},

pages = {432},

abstract = {Honeybee products have been among important consumer products throughout history. Microbiota has attracted attention in recent years due to both their probiotic value and industrial potential. Fructophilic lactic acid bacteria (FLAB), whose field of study has been expanding rapidly in the last 20 years, are among the groups that can be isolated from the bee gut. This study aimed to isolate FLAB from the honeybees of two different geographic regions in Turkey and investigate their probiotic, metabolic and anti-quorum sensing (anti-QS) potential. Metabolic properties were investigated based on fructose toleration and acid and diacetyl production while the probiotic properties of the isolates were determined by examining pH, pepsin, pancreatin resistance, antimicrobial susceptibility, and antimicrobial activity. Anti-QS activities were also evaluated with the Chromobacterium violaceum biosensor strain. Two FLAB members were isolated and identified by the 16S rRNA analysis as Fructobacillus tropaeoli and Apilactobacillus kunkeei, which were found to be tolerant to high fructose, low pH, pepsin, pancreatin, and bile salt environments. Both isolates showed anti-QS activity against the C. violaceum biosensor strain and no diacetyl production. The daily supernatants of the isolates inhibited the growth of Enterococcus faecalis ATCC 29212 among the selected pathogens. The isolates were found resistant to kanamycin, streptomycin, erythromycin, and clindamycin. In the evaluation of the probiotic potential of these species, the negative effect of antibiotics and other chemicals to which honeybees are directly or indirectly exposed draws attention within the scope of the "One Health" approach.},

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pubstate = {published},

tppubtype = {article}

}

@article{pmid33866380,

title = {Microbial exopolysaccharide production of Streptococcus thermophilus and its antiquorum sensing activity},

author = {Demet Genc Karadeniz and Banu Kaskatepe and Merve Eylul Kiymaci and Kenan Can Tok and Mehmet Gumustas and Cigdem Karaaslan},

doi = {10.1007/s00203-021-02313-7},

issn = {1432-072X},

year  = {2021},

date = {2021-08-01},

journal = {Arch Microbiol},

volume = {203},

number = {6},

pages = {3331--3339},

abstract = {Interest in the production of exopolysaccharides by microorganisms has increased in the recent years. Using low-cost product is the main step of microbial production to reduce cost and compete with chemical production. In this work, EPS production of Streptococcus thermophilus isolates from yogurt (S2), kefir (S3), and S. thermophilus ATCC 19258 (S1) isolate which was used as control strains were investigated by using different fruit pulps. S. thermophilus isolates were identified by morphological and 16S sequence analysis. The amount of EPS obtained was measured spectrophotometrically using glucose as standard with phenol sulfuric acid method. All three isolates produced higher amounts of EPS on M17 medium than Nutrient medium. When the fruit pulp was added to the medium, EPS production increased in all three isolates. When different nitrogen sources were added together with fruit pulp juice, EPS production increased. The highest amount of EPS produced by ATCC 19258 strain (21.570 mg/L) and S3 isolate (29.131 mg/L) is the medium where mixed fruit pulp juice and nitrogen source is tryptophan. It has been shown that EPS production is increased by adding fruit pulps to the prepared media. It is thought that apricot pulp can be a good alternative in EPS production especially in the evaluation of wastes. Also, antiquorum sensing activity of the highest amount EPS was determined by using Chromobacterium violaceum CV026 strain and found effective on violacein pigment inhibition and C6-AHL production of biosensor strain.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid33322449,

title = {The Effect of Enantiomer Elution Order on the Determination of Minor Enantiomeric Impurity in Ketoprofen and Enantiomeric Purity Evaluation of Commercially Available Dexketoprofen Formulations},

author = {Kenan Can Tok and Mehmet Gumustas and Giorgi Jibuti and Halit Sinan Suzen and Sibel A Ozkan and Bezhan Chankvetadze},

doi = {10.3390/molecules25245865},

issn = {1420-3049},

year  = {2020},

date = {2020-12-01},

journal = {Molecules},

volume = {25},

number = {24},

abstract = {In a recent study, opposite enantiomer elution order was observed for ketoprofen enantiomers on two amylose-phenylcarbamate-based chiral columns with the same chemical composition of the chiral selector but in one case with coated while in the other with an immobilized chiral selector. In the present study, the influence of this uncommon effect on method validation parameters for the determination of minor enantiomeric impurity in dexketoprofen was studied. The validated methods with two alternative elution orders for enantiomers were applied for the evaluation of enantiomeric impurity in six marketed dexketoprofen formulations from various vendors. In most of these formulations except one the content of enantiomeric impurity exceeded 0.1% (/).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid32644279,

title = {A novel stability-indicating analytical method development for simultaneous determination of carboplatin and decitabine from nanoparticles},

author = {Ozge Esim and Mehmet Gumustas and Canan Hascicek and Sibel A Ozkan},

doi = {10.1002/jssc.202000320},

issn = {1615-9314},

year  = {2020},

date = {2020-09-01},

journal = {J Sep Sci},

volume = {43},

number = {17},

pages = {3491--3498},

abstract = {Drug resistance is one of the main problems of cancer treatment. For this reason, combination therapy is commonly used for years. The combination of a chemotherapeutic, carboplatin, and the epigenetic drug decitabine is a new approach to modulate drug resistance. Nanoparticulate systems can overcome the drawbacks associated with the drug combinations. An analytical method that can detect and quantify carboplatin and decitabine which is encapsulated into the nanoparticles is necessary for nanoparticle development. In the literature, there is no analytical method in which carboplatin and decitabine are determined simultaneously. The primary purpose of this study is to develop and validate a novel, and stability-indicating high-performance liquid chromatography method for simultaneous determination of carboplatin and decitabine in pharmaceutical preparations in addition to developing the first nanoformulation for this drug combination. Therefore, various experimental parameters were optimized. The chromatographic separation was achieved using an XSelect CSH C18 (250 × 4.6 mm I.D., 5 µm) column and a mobile phase consisting of methanol:water (containing 0.1% phosphoric acid) (3:97, v/v). The mobile phase pH was adjusted to 7.0 with 5 M NaOH. The developed method was successfully applied for the simultaneous determination and quantification of carboplatin and decitabine co-encapsulated in nanoparticles and released into in vitro dissolution medium.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30900263,

title = {Separation of brombuterol enantiomers in capillary electrophoresis with cyclodextrin-type chiral selectors and investigation of structure of selector-selectand complexes using nuclear magnetic resonance spectroscopy},

author = {Ann Gogolashvili and Elene Tatunashvili and Lali Chankvetadze and Tamas Sohajda and Mehmet Gumustas and Sibel A Ozkan and Antonio Salgado and Bezhan Chankvetadze},

doi = {10.1002/elps.201900062},

issn = {1522-2683},

year  = {2019},

date = {2019-08-01},

journal = {Electrophoresis},

volume = {40},

number = {15},

pages = {1904--1912},

abstract = {The major goal of this study was to determine the affinity pattern of brombuterol (BB) enantiomers toward various cyclodextrins (CD) and to evaluate the potential of NMR spectroscopy for understanding fine mechanisms of interactions between CDs and BB enantiomers. Separation of BB enantiomers was performed in a fused-silica capillary using a phosphate buffer, pH 2.5, at the room temperature in the normal polarity mode. It was shown once again that CE in combination with NMR spectroscopy represents a very sensitive tool for studies of affinity patterns and structure of CD complexes with chiral guests. Although opposite affinity patterns of BB enantiomers were observed toward native β- and γ-CDs, no significant differences between the structures of the complexes of these two CDs with BB were detected by NMR spectroscopy. In contrary to this, the opposite affinity pattern of BB enantiomers toward β-CD and its two sulfated derivatives, heptakis (2,3-O-diacetyl-6-sulfo)-β-CD (HDAS-β-CD) and heptakis (2-O-methyl-3,6-di-O-sulfo)-β-CD (HMDS-β-CD) was associated with major differences in the structure of the complexes. In addition, it was shown again that HMDS-β-CD provides separation of enantiomers without formation of inclusion-type complex with the chiral analyte.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid30595027,

title = {Modern Assay Techniques for Cancer Drugs: Electroanalytical and Liquid Chromatography Methods},

author = {Sevinc Kurbanoglu and Nurgul K Bakirhan and Mehmet Gumustas and Sibel A Ozkan},

doi = {10.1080/10408347.2018.1527206},

issn = {1547-6510},

year  = {2019},

date = {2019-01-01},

journal = {Crit Rev Anal Chem},

volume = {49},

number = {4},

pages = {306--323},

abstract = {In the past decades, patients who have chemotherapy treatment have considerably increased number. At this point, the development of rapid precise, and reliable methods are very important to analyze cancer drugs from their dosage forms, animals or human biological samples. Among all the analytical methods, electrochemical methods hold an important position with their unique properties such as specificity in the biological recognition process, fast response, and their reliability and do not need a pretreatment process. Chromatographic methods are also used in a wide range of analytical applications for the analyses of anticancer drugs. The power of chromatography comes from its ability to separate a mixture of analytes and determination of their concentrations. Chromatographic techniques can mainly be divided into gas, liquid, and supercritical fluid chromatography. In the frame of this information, this review is aimed to provide basic principles of electroanalytical and high-performance liquid chromatography methods for the analysis of cancer drugs. In addition, some selected applications for electrochemistry-related techniques and high-performance liquid chromatography, for the determination of anti-cancer pharmaceuticals published in the last five years are also discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30093095,

title = {Separation of terbutaline enantiomers in capillary electrophoresis with cyclodextrin-type chiral selectors and investigation of structure of selector-selectand complexes},

author = {Ann Gogolashvili and Elene Tatunashvili and Lali Chankvetadze and Tamas Sohajda and Julianna Szeman and Mehmet Gumustas and Sibel A Ozkan and Antonio Salgado and Bezhan Chankvetadze},

doi = {10.1016/j.chroma.2018.08.012},

issn = {1873-3778},

year  = {2018},

date = {2018-10-01},

journal = {J Chromatogr A},

volume = {1571},

pages = {231--239},

abstract = {The affinity pattern of terbutaline enantiomers towards various cyclodextrins was studied using capillary electrophoresis. The affinity pattern of terbutaline enantiomers was the same towards all studied cyclodextrins except heptakis(2-O-methyl-3,6-di-O-sulfo)-β-CD. Nuclear magnetic resonance spectroscopy was used for understanding of fine structural mechanisms of interactions of β-cyclodextrin and its two sulfated derivatives with the enantiomers of terbutaline. The structure of terbutaline complexes with all 3 cyclodextrins studied was different from each other. In confirmation with our earlier studies it was shown again that capillary electrophoresis represents very sensitive technique for studies of affinity patterns in cyclodextrin complexes with chiral guests. Other instrumental (e.g. NMR spectroscopy and X-ray diffraction analysis) and theoretical techniques, although very useful for obtaining the information regarding the stoichiometry, binding constants and structure of intermolecular complexes, as well as about the forces involved in selector-selectand binding and chiral recognition, may sometimes fail to properly sense those fine differences in the affinity patterns. Therefore, it is recommended to use capillary electrophoresis in order to examine correctness of affinity pattern determined for intermolecular complexes of cyclodextrins with guest molecules by other instrumental or computation techniques.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid30098733,

title = {Application of cellulose 3,5-dichlorophenylcarbamate covalently immobilized on superficially porous silica for the separation of enantiomers in high-performance liquid chromatography},

author = {Lia Bezhitashvili and Anna Bardavelidze and Antonina Mskhiladze and Mehmet Gumustas and Sibel A Ozkan and Alessandro Volonterio and Tivadar Farkas and Bezhan Chankvetadze},

doi = {10.1016/j.chroma.2018.08.011},

issn = {1873-3778},

year  = {2018},

date = {2018-10-01},

journal = {J Chromatogr A},

volume = {1571},

pages = {132--139},

abstract = {Our earlier studies have demonstrated the applicability of polysaccharide-based chiral selectors in combination with superficially porous (or core-shell) silica (SPS) particles for the preparation of highly efficient chiral stationary phases (CSP). In earlier studies, CSPs were prepared by coating (adsorption) of the chiral selector onto the surface of silica. In this study we report for the first time the CSP obtained by covalent immobilization of a chiral selector onto the surface of SPS particles. The applicability of this CSP for the separation of enantiomers in pure methanol and acetonitrile, as well as in n-hexane/2-propanol mobile phases is shown. The effect of the injected sample amount, mobile phase flow rate and detection frequency on separation performance were studied, as well as high efficiency separation of enantiomers with the analysis time less than 30 s was attempted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29807134,

title = {Quorum sensing signals and related virulence inhibition of Pseudomonas aeruginosa by a potential probiotic strain's organic acid},

author = {Merve Eylul Kiymaci and Nurten Altanlar and Mehmet Gumustas and Sibel A Ozkan and Ahmet Akin},

doi = {10.1016/j.micpath.2018.05.042},

issn = {1096-1208},

year  = {2018},

date = {2018-08-01},

journal = {Microb Pathog},

volume = {121},

pages = {190--197},

abstract = {Studies conducted in recent years show that pathogen bacteria are not asocial assets and they use the cell to cell communication mechanism called quorum sensing that depends on population density to adapt changing environmental conditions. This mechanism is coordinate gene expression of various bacterial factors like bioluminescence, antibiotic biosynthesis, plasmid conjugation and virulence. Bacteria communicate with each other by producing signal molecules and regulate the production of virulence factors that have importance in the pathogenity formation. Virulence mechanisms of Pseudomonas aeruginosa, which causes various types of infections in humans, are also regulated by quorum sensing. Nowadays, biotechnological researches are focused on the development of homoserine lactone antagonists. The use of these type of molecules are considered to be a new treatment approach for blocking communication between bacteria and reducing virulence, therefore improving infection control. In this study, lactic acid of a potential probiotic Pediococcus acidilactici M7 strain isolated from newborn faeces was used to evaluate the inhibitory effect on quorum sensing signal molecules and some virulence factors of clinical Pseudomonas aeruginosa isolates. Results showed that lactic acid has an inhibitory effect on short-chain HSL production and swarming-swimming-twitching motility, elastase, protease, pyocyanin, and biofilm production of Pseudomonas aeruginosa isolates in certain quantities that are regulated by the quorum sensing system.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29637614,

title = {Development of stability indicating HPLC method for the separation and validation of enantiomers of miconazole},

author = {Nadia Bounoua and Khaled Sekkoum and Mehmet Gumustas and Nasser Belboukhari and Sibel A Ozkan},

doi = {10.1002/chir.22858},

issn = {1520-636X},

year  = {2018},

date = {2018-06-01},

journal = {Chirality},

volume = {30},

number = {6},

pages = {807--815},

abstract = {A selective and sensitive stability indicting HPLC method was developed for the analysis of enantiomers of miconazole. For this purpose, six different polysaccharide-based chiral columns were evaluated. Optimization was performed using several polar organic and alcohol-hydrocarbon mobile phases. As a result of optimization studies, the analysis was carried out using Lux Cellulose-3, methanol as a mobile phase at a flow rate of 1 mL·min , and the detection wavelength was arranged to 230 nm. Developed method has been fully validated according to International Council on Harmonization guidelines. Method was found linear in the concentration range of 1 to 200 μg·mL . Coefficient of determination (R ) was calculated as 0.9996, intraday precision of the method was found with the RSD% of 0.56, and the recovery of the method was calculated close to 100%. Furthermore, some other validation parameters like specificity, selectivity, LOD, and LOQ were also investigated. Stability indicating capability of this method was shown by forced degradation studies, and the run time for each analysis was less than 6 minutes. As a result, simple, fast, reliable HPLC method was developed for the separation and determination of the enantiomers of miconazole. Applicability of the developed method was shown with the application of marketed pharmaceutical preparations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29567571,

title = {Development of a HILIC method for the determination of 5-fluorouracil from nano drug delivery systems and rat skin extracts},

author = {Gulin Amasya and Mehmet Gumustas and Ulya Badilli and Sibel A Ozkan and Nilufer Tarimci},

doi = {10.1016/j.jpba.2018.03.021},

issn = {1873-264X},

year  = {2018},

date = {2018-05-01},

journal = {J Pharm Biomed Anal},

volume = {154},

pages = {285--293},

abstract = {This is the first report in literature using hydrophilic interaction liquid chromatography (HILIC) in combination with diode array detector (DAD) for stability indicating determination of 5-Fluorouracil (5-FU) from its bulk form, pharmaceutical preparations, developed solid lipid nanoparticle (SLN) and nano structured lipid carrier (NLC) drug delivery systems as well as the rat skin extracts. The separation was performed at 45 °C, on Sequant Zic HILIC (250 mm × 4.60 mm ID, 5 μm, 200 A), peek HPLC column. Mobile phase is consisting of a mixture of acetonitrile: buffer containing 5 mM ammonium acetate (95:5; v/v). The pH of the mobile phase was adjusted to 7.0 using 1 M NaOH. The analysis was carried out at 0.75 mL min flow rate with a detection wavelength of 265 nm and the injection volume was arranged as 10 μL. The developed method was fully validated in accordance with the International Council on Harmonization (ICH) Guidelines. Specificity of this method was demonstrated by forced degradation studies. As a result of calibration studies, the calibration curve was found linear in the concentration range of 1-250 μg mL (R = 0.999). The precision of this technique calculated within the frame of intra-day and inter-day based on a percentage of relative standard deviation (RSD%) values (<2%). The limits of detection and quantification were 11 and 37 ng mL respectively. On the other hand, 5-FU loaded SLN and NLC formulations with average particle size of 370 nm were also developed and compared in order to increase the permeation of drug into the rat skin. Ex-vivo Penetration/Permeation Studies indicated that higher dermal accumulation of 5-FU was obtained with NLC formulation. As a conclusion, the present work expressed the optimization and the validation of a selective, simple, precise and accurate fully validated HILIC method with sufficient sensitivity for the estimation of 5-FU in raw materials, marketed formulation and rat skin extract after applying both of the commercial product and newly developed nanoparticulate drug delivery systems on to the rat skins with high percentage recoveries.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29216682,

title = {Simultaneous determination and validation of emtricitabine, rilpivirine and tenofovir from biological samples using LC and CE methods},

author = {Mehmet Gumustas and Mehmet Gokhan Caglayan and Feyyaz Onur and Sibel A Ozkan},

doi = {10.1002/bmc.4158},

issn = {1099-0801},

year  = {2018},

date = {2018-04-01},

journal = {Biomed Chromatogr},

volume = {32},

number = {4},

abstract = {A combination of antiretroviral agents is frequently used in effective treatment of the human immunodeficiency virus infection. In this study, two different separation methods are presented for the simultaneous determination of emtricitabine, rilpivirine and tenofovir from raw materials and urine samples. Developed liquid chromatography and capillary electrophoresis methods were thoroughly optimized for high analytical performances. Optimization of multiple variables at the same time by performing a minimum number of experiments was achieved by the Box-Behnken design, which is an experimental design in response surface methodology, in capillary electrophoresis. The results of the experimental design ensure minimum analysis time with well-separated analytes. Separation conditions, such as different stationary phases, pH level, organic modifiers and temperatures in liquid chromatography method, were also optimized. In particular, among stationary phases, the core-shell column especially enhanced the effectiveness of separation in liquid chromatography. Both methods were fully validated and applied to real samples. The main advantage of the developed methods is the separation of the drug combination in a short time with high efficiency and without any time-consuming steps.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid29376488,

title = {Analytical and Preparative Scale Separation of Enantiomers of Chiral Drugs by Chromatography and Related Methods},

author = {Mehmet Gumustas and Sibel A Ozkan and Bezhan Chankvetadze},

doi = {10.2174/0929867325666180129094955},

issn = {1875-533X},

year  = {2018},

date = {2018-01-01},

journal = {Curr Med Chem},

volume = {25},

number = {33},

pages = {4152--4188},

abstract = {While the amino acids, enzymes and hormones are chiral, chirality plays significant role in the life of plants, animals, as well as the human being. Chirality of molecules is important in various industries, such as pharmaceutical, agricultural, food, electronics, etc. Chiral drugs may have different bioavailability, distribution, biotransformation and excretion, as well as quantitatively and/or qualitatively different pharmacological or toxic properties. Enantiomerically pure chiral drugs have been increasingly developed for the pharmaceutical market due to their superiority from the viewpoints of potency and safety. This is supported by the development of new methods for enantioselective production of the chiral compounds, as well as by the capability of the enantioselective analytical methods to allow a detection and quantification of minor enantiomeric impurity in the presence of another enantiomer in a large excess. The aim of the present review is to provide a short summary of the basic principles of chiral separations on an analytical and preparative scale. In addition, some selected applications for analytical techniques, such as gas chromatography, supercritical fluid chromatography, high performance liquid chromatography, capillary electrophoresis and capillary electrochromatography for the separation of enantiomers of chiral pharmaceuticals published in the last two years are also discussed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27522152,

title = {Separation and elution order of the enantiomers of some β-agonists using polysaccharide-based chiral columns and normal phase eluents by high-performance liquid chromatography},

author = {Mehmet Gumustas and Sibel Aysil Ozkan and Bezhan Chankvetadze},

doi = {10.1016/j.chroma.2016.08.011},

issn = {1873-3778},

year  = {2016},

date = {2016-10-01},

journal = {J Chromatogr A},

volume = {1467},

pages = {297--305},

abstract = {In this study separation of enantiomers of 8 chiral β-agonists were studied on 6 polysaccharide-based chiral columns in polar-organic and alcohol-hydrocarbon mobile phases. No separation of enantiomers was observed on any column with polar-organic mobile phase eluents such as pure methanol, ethanol or acetonitrile. Most of the chiral analytes were resolved into enantiomers when alcohol-hydrocarbon type mobile phases were used. The most successful column was Lux Cellulose-2 on which all 8 chiral analytes were baseline resolved into enantiomers at least with one mobile phase used. The reversal of enantiomer elution order was observed dependent on the chemistry of the chiral selector and the composition of the mobile phase.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26952922,

title = {Determination of antazoline and tetrahydrozoline in ophthalmic solutions by capillary electrophoresis and stability-indicating HPLC methods},

author = {Mehmet Gumustas and Usama Alshana and Nusret Ertas and Nilgun Gunden Goger and Sibel A Ozkan and Bengi Uslu},

doi = {10.1016/j.jpba.2016.02.032},

issn = {1873-264X},

year  = {2016},

date = {2016-05-01},

journal = {J Pharm Biomed Anal},

volume = {124},

pages = {390--398},

abstract = {Capillary electrophoretic (CE) and high performance liquid chromatographic (HPLC) methods were developed and optimized for the determination of antazoline (ANT) and tetrahydrozoline (TET) in ophthalmic formulations. Optimum electrophoretic conditions were achieved using a background electrolyte of 20mM phosphate buffer at pH 7.0, a capillary temperature of 25°C, a separation voltage of 22 kV and a pressure injection of the sample at 50 mbar for 17s. HPLC analysis was performed with Kinetex (150 × 4.6mm ID × 5 μm) (Phenomenex, USA) analytical column with 1 mL min(-1) flow rate of mobile phase which consisted of 0.05% TFA in bidistilled water (pH adjusted to 3.0 with 5M NaOH) and acetonitrile/buffer in the ratio of 63:37 (v/v) at room temperature. Injection volume of the samples was 10 μL and the wavelength of the detector was set at 215 nm for monitoring both analytes. Calibration graphs showed a good linearity with a coefficient of determination (R(2)) of at least 0.998 for both methods. Intraday and interday precision (expressed as RSD%) were lower than 2.8% for CE and 0.92% for HPLC. The developed methods were demonstrated to be simple and rapid for the determination of ANT and TET in ophthalmic solutions providing recoveries in the range between 97.9 and 102.70% for CE and HPLC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26971031,

title = {A selective and sensitive stability-indicating HPLC method for the validated assay of etoposide from commercial dosage form and polymeric tubular nanocarriers},

author = {Aslihan Hilal Algan and Mehmet Gumustas and Aysegul Karatas and Sibel A Ozkan},

doi = {10.1016/j.jpba.2016.03.007},

issn = {1873-264X},

year  = {2016},

date = {2016-05-01},

journal = {J Pharm Biomed Anal},

volume = {124},

pages = {382--389},

abstract = {Etoposide is a topoisomerase II enzyme inhibitor type chemotherapeutic agent which is widely used in the therapy of various cancers. Its short half-life and toxicity to normal tissues are the major drawbacks in its clinical applications. Polymeric nanoparticulate drug delivery systems are rational carriers to deliver etoposide with higher efficiency and fewer side effects. In addition tubular shaped drug carriers are found to show a great potential for drug delivery on the basis of promising results regarding particle shape and cellular uptake. In this study, etoposide loaded polymeric tubular nanocarriers have been developed by template wetting method using porous anodic aluminum oxide membranes as templates. The developed poly(methyl methacrylate) nanocarriers were evaluated for structural analysis, in vitro drug release studies and drug release kinetics. Accurate and reliable determination of the drug release from newly developed nanocarriers, is of great importance. For this reason a selective and sensitive reversed phase liquid chromatography method was developed and fully validated from the point of system suitability, specificity, linearity and range, limit of detection (LOD), limit of quantification (LOQ), precision, accuracy and robustness for the reliable determination of etoposide. Stability indicating capability was shown with forced degradation studies and the chromatographic conditions were optimized on ACE 5C18 (150 mm × 4.6mm I.D., 5 μm) analytical column. Related to the calibration results ETP was found linear in the range between 0.2 from 100 μg mL(-1) with the LOD as 0.015 μg.mL(-1). The resultant conditions were applied for the selective and sensitive determination of etoposide from its commercial dosage form with the high accuracy values (99.82-100.65%). The method was successfully detected assay of etoposide release from newly developed polymeric tubular nanocarriers, which was found as 72.2% at the end of 24h.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27169190,

title = {Comparison of Seeds of Colchicum speciosum and Gloriosa superba in respect to Colchicine and Colchicoside Contents by RP-LC},

author = {Mehmet Gumustas and Derya Çiçek Polat and Ceyda S Kiliç and Kemalettin Akalin and Sibel A Ozkan and Maksut Coşkun},

issn = {1934-578X},

year  = {2016},

date = {2016-03-01},

journal = {Nat Prod Commun},

volume = {11},

number = {3},

pages = {397--400},

abstract = {In this study, colchicine (CLN) and colchicoside (CLS) contents of the methanolic extracts of the seeds of Colchicum speciosum Steven that were collected from Uzungöl, Trabzon and also the seeds belonging to two different samples of Gloriosa superba Linn. imported from India were compared by using RP-LC (Reversed Phase High Pressure Liquid Chromatography). This proposed method is advantageous in terms of sample preparation and selective separation of the compounds. Also the method was successfully validated in accordance with the International Conference on Harmonization (ICH) guideline acceptance criteria for system suitability, linearity and range, precision, specificity and accuracy. As a conclusion of this analysis, the colchicoside and colchicine contents of G. superba (GSI), G. superba (GSII) and C. speciosum (CS) were found to be 312.9 mg/100 g and 333.1 mg/100 g; 434.0 mg/100 g and 471.1 mg/100 g, and 51.9 mg/100 g and 75.9 mg/100 g, respectively.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26413070,

title = {Biosurfactant production by Pseudomonas aeruginosain kefir and fish meal},

author = {Banu Kaskatepe and Sulhiye Yildiz and Mehmet Gumustas and Sibel A Ozkan},

doi = {10.1590/S1517-838246320140727},

issn = {1678-4405},

year  = {2015},

date = {2015-01-01},

journal = {Braz J Microbiol},

volume = {46},

number = {3},

pages = {855--859},

abstract = {The aim of this study was to increase rhamnolipid production by formulating media using kefir and fish meal for Pseudomonas aeruginosa strains isolated from different environmental resources. The strains, named as H1, SY1, and ST1, capable of rhamnolipid production were isolated from soil contaminated with wastes originating from olive and fish oil factories. Additionally, P. aeruginosa ATCC 9027 strain, which is known as rhamnolipid producer, was included in the study. Initially, rhamnolipid production by the strains was determined in Mineral Salt Medium (MSM) and then in media prepared by using kefir and fish meal. The obtained rhamnolipids were purified and quantified according to Dubois et al. (1956). The quantity of rhamnolipids of ATCC, H1 and SY1 strains in kefir media were determined as 11.7 g/L, 10.8 g/L and 3.2 g/L, respectively, and in fish meal media as 12.3 g/L, 9.3 g/L and 10.3 g/L, respectively. In addition, effect of UV light exposure on rhamnolipid production was also investigated but contrary a decrease was observed. The results indicate that P. aeruginosa strains isolated from various environmental resources used in this study can be important due to their rhamnolipid yield, and fish meal, which is obtained from waste of fish, can be an alternative source in low cost rhamnolipid production.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24861889,

title = {Optimization of a validated stability-indicating RP-LC method for the determination of fulvestrant from polymeric based nanoparticle systems, drugs and biological samples},

author = {Mehmet Gumustas and Ceyda Tuba Sengel-Turk and Canan Hascicek and Sibel A Ozkan},

doi = {10.1002/bmc.3183},

issn = {1099-0801},

year  = {2014},

date = {2014-10-01},

journal = {Biomed Chromatogr},

volume = {28},

number = {10},

pages = {1409--1417},

abstract = {Fulvestrant is used for the treatment of hormone receptor-positive metastatic breast cancer in postmenopausal women with disease progression following anti-estrogen therapy. Several reversed-phase columns with variable silica materials, diameters, lengths, etc., were tested for the optimization study. A good chromatographic separation was achieved using a Waters X-Terra RP(18) column (250 × 4.6 mm i.d. × 5 µm) and a mobile phase, consisting of a mixture of acetonitrile-water (65:35; v/v) containing phosphoric acid (0.1%). The separation was carried out 40 °C with detection at 215 nm.The calibration curves were linear over the concentration range between 1.0-300 and 1.0-200 µg/mL for standard solutions and biological media, respectively. The proposed method is accurate and reproducible. Forced degradation studies were also realized. This fully validated method allows the direct determination of fulvestrant in dosage form and biological samples. The average recovery of the added fulvestrant amount in the samples was between 98.22 and 104.03%. The proposed method was also applied for the determination of fulvestrant from the polymeric-based nanoparticle systems. No interference from using polymers and other excipients was observed in in vitro drug release studies. Therefore an incorporation efficiency of fulvestrant-loaded nanoparticle could be determined accurately and specifically.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24810231,

title = {Dynamic computer simulation of electrophoretic enantiomer migration order and separation in presence of a neutral cyclodextrin},

author = {Wolfgang Thormann and Lali Chankvetadze and Mehmet Gumustas and Bezhan Chankvetadze},

doi = {10.1002/elps.201400193},

issn = {1522-2683},

year  = {2014},

date = {2014-10-01},

journal = {Electrophoresis},

volume = {35},

number = {19},

pages = {2833--2841},

abstract = {One-dimensional dynamic computer simulation was employed to investigate the separation and migration order change of ketoconazole enantiomers at low pH in presence of increasing amounts of (2-hydroxypropyl)-β-cyclodextrin (OHP-β-CD). The 1:1 interaction of ketoconazole with the neutral cyclodextrin was simulated under real experimental conditions and by varying input parameters for complex mobilities and complexation constants. Simulation results obtained with experimentally determined apparent ionic mobilities, complex mobilities, and complexation constants were found to compare well with the calculated separation selectivity and experimental data. Simulation data revealed that the migration order of the ketoconazole enantiomers at low (OHP-β-CD) concentrations (i.e. below migration order inversion) is essentially determined by the difference in complexation constants and at high (OHP-β-CD) concentrations (i.e. above migration order inversion) by the difference in complex mobilities. Furthermore, simulations with complex mobilities set to zero provided data that mimic migration order and separation with the chiral selector being immobilized. For the studied CEC configuration, no migration order inversion is predicted and separations are shown to be quicker and electrophoretic transport reduced in comparison to migration in free solution. The presented data illustrate that dynamic computer simulation is a valuable tool to study electrokinetic migration and separations of enantiomers in presence of a complexing agent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23947602,

title = {Preparation and characterization of chitosan-based spray-dried microparticles for the delivery of clindamycin phosphate to periodontal pockets},

author = {Muge Kilicarslan and Mehmet Gumustas and Sulhiye Yildiz and Tamer Baykara},

doi = {10.2174/15672018113109990055},

issn = {1875-5704},

year  = {2014},

date = {2014-01-01},

journal = {Curr Drug Deliv},

volume = {11},

number = {1},

pages = {98--111},

abstract = {Biodegradable spray-dried chitosan microparticles loaded with clindamycin phosphate (CDP) were formulated to deliver drugs locally into the periodontal pocket. The effects of spray dryer conditions, drug/polymer ratio, and added amounts of glutaraldehyde (GA) solution on the characterization of microparticles were investigated by determining process yield, encapsulation efficiency, particle size and size distribution, surface morphology, drug release, release kinetics, thermal analysis, and antimicrobial efficacy of formulations. Burst release was obtained for all formulations due to the water solubility of the drug, but the increased amount of chitosan decreased the drug release rates. Microparticles with a more wrinkled surface were obtained by increasing the amount of the drug. Incorporation efficiencies higher than 80% were obtained for all preparation conditions. The addition of GA caused higher viscosity of the chitosan solution, leading to larger particles with more spherical and smooth surface characteristics. However, the increased GA amount did not significantly influence the drug release. The data obtained from in vitro release experiments were best fitted to the Weibull and Higuchi models. The amorphous nature of the drug-loaded microparticles was detected by differential scanning calorimetric (DSC) thermographs. A delayed drug release of more than one week could be obtained by loading the drug into the chitosan microparticles. Antimicrobial efficacy studies reflected a positive drug release profile. These results indicate that spray-dried clindamycin-loaded microparticles with sustained antimicrobial efficacy appear to be a promising periodontal therapy for drug delivery into the periodontal pocket.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22994658,

title = {Antioxidant activity of indole-based melatonin analogues in erythrocytes and their voltammetric characterization},

author = {Sibel Suzen and Betul Tekiner-Gulbas and Hanif Shirinzadeh and Duysal Uslu and Hande Gurer-Orhan and Mehmet Gumustas and Sibel Aysil Ozkan},

doi = {10.3109/14756366.2012.717223},

issn = {1475-6374},

year  = {2013},

date = {2013-12-01},

journal = {J Enzyme Inhib Med Chem},

volume = {28},

number = {6},

pages = {1143--1155},

abstract = {Melatonin (MLT) is a strong free-radical scavenger, which protects the body from the effects of oxidants. In recent years, MLT have been described resulting in much attention in the development of synthetic compounds possessing. As a part of our ongoing study a series of indole-based MLT analogue hydrazide/hydrazone derivatives were synthesized, characterized and in vitro antioxidant activity was investigated by evaluating their reducing effect against oxidation of a redox sensitive fluorescent probe. Membrane stabilizing effect of all compounds was also investigated by lactate dehydrogenase leakage assay. Furthermore voltammetric methods have been applied to the synthesized compounds to characterize oxidation potentials to get insight into their metabolism owing to the oxidation mechanisms taking place at the electrode and in the body share similar principles.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23513956,

title = {Fully validated simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in their dosage forms using different voltammetric, chromatographic, and spectrophotometric analytical methods},

author = {Burcin Bozal and Mehmet Gumustas and Burcu Dogan-Topal and Bengi Uslu and Sibel A Ozkan},

doi = {10.5740/jaoacint.11-364},

issn = {1060-3271},

year  = {2013},

date = {2013-01-01},

journal = {J AOAC Int},

volume = {96},

number = {1},

pages = {42--51},

abstract = {Voltammetric, chromatographic, and spectrophotometric methods were developed for the simultaneous determination of bisoprolol fumarate (BIS) and hydrochlorothiazide (HCZ). Differential pulse and square wave voltammetry techniques were used to analyze BIS and HCZ simultaneously by measuring at about 1400 and 1100 mV, respectively. RP-HPLC was the second method for simultaneous analysis of the compounds. The mixture of BIS, HCZ, and moxifloxacin as an internal standard was separated on an RP Zorbax Eclipse XDB-C18 column (150 x 4.6 mm, id, 5 microm particle size) using acetonitrile-15 mM phosphate (25+75, v/v) mobile phase at a 1.0 mL/min flow rate. The third method was based on first derivative of the ratio-spectra method obtained from the measurements of the amplitudes at 246 and 257 nm for BIS and HCZ, respectively. All the proposed methods were effectively applied for the simultaneous determination of BIS and HCZ in tablet dosage forms without any time-consuming extraction, sample preparation, or derivatization procedures.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid23088923,

title = {Simultaneous estimation and validation of some binary mixtures of antihypertensive drugs by RP-LC methods using two new generation silica columns},

author = {Sevinc Kurbanoglu and Mehmet Gumustas and Sibel A Ozkan},

doi = {10.1016/j.jpba.2012.08.018},

issn = {1873-264X},

year  = {2013},

date = {2013-01-01},

journal = {J Pharm Biomed Anal},

volume = {72},

pages = {198--201},

abstract = {Two reversed phase liquid chromatographic (RP-LC) techniques are presented for the rapid, accurate, precise, simultaneous determination of olmesartan-hydrochlorothiazide and zofenopril-hydrochlorothiazide binary mixtures in their dosage forms. The separation of these binary mixtures was carried out by using two new stationary phases that have different surface chemistries which were used for the first time in the determination of these binary mixtures. The analyte peaks were detected at 216 nm. Linearity was obtained in different concentration ranges between 0.5 and 20 μg mL(-1) for all compounds. The proposed methods have been extensively validated and sample preparation, flow rate, run time of the analytical systems were at low levels. The proposed methods would decrease the consumption of organic solvents and reagents further safeguarding to our environment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24000747,

title = {A validated stability-indicating RP-LC method for the simultaneous determination of amlodipine and perindopril in tablet dosage form and their stress degradation behavior under ICH-recommended stress conditions},

author = {Mehmet Gumustas and Sibel A Ozkan},

doi = {10.5740/jaoacint.11-010},

issn = {1060-3271},

year  = {2013},

date = {2013-01-01},

journal = {J AOAC Int},

volume = {96},

number = {4},

pages = {751--757},

abstract = {A stability-indicating RP-LC assay method was developed for the simultaneous determination of the cardiovascular drugs amlodipine and perindopril in the presence of degradation products generated from forced decomposition studies. The developed method is applicable for the determination of related substances in bulk drugs and simultaneous assay in a tablet pharmaceutical dosage form. Separation of the drugs and their degradation products was obtained using an RP Waters Spherisorb ODS1 column (250 x 4.6 mm id, 5 pm particle size) with the mobile phase acetonitrile-water (30 + 70, v/v) containing 15 mM phosphoric acid. The pH of the mobile phase was adjusted to 5.0. A flow rate of 1.2 mL/min was used for the separations, with detection at 215 nm. The chromatographic separation was performed at a column temperature of 45 degrees C. Atenolol was chosen as the internal standard. Amlodipine and perindopril were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Degradation studies showed that both compounds were degraded under these stress conditions. The method was found to be stability-indicating and can be used for the routine analysis of amlodipine and perindopril in the studied combined tablet dosage form.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid22483669,

title = {Voltammetric and RP-LC assay for determination of benidipine HCl},

author = {Nurgul Karadas and Senem Sanli and Mehmet Gumustas and Sibel A Ozkan},

doi = {10.1016/j.jpba.2012.03.025},

issn = {1873-264X},

year  = {2012},

date = {2012-07-01},

journal = {J Pharm Biomed Anal},

volume = {66},

pages = {116--125},

abstract = {The detailed electrooxidative behavior of benidipine (BEN) has been studied by using glassy carbon (GC) and boron-doped diamond (BDD) electrodes. Using cyclic voltammetry, depending on the pH values and the working electrodes, BEN showed one or two sharp and irreversible oxidation responses. The voltammetric experiments on some model compounds allowed elucidation of the oxidation mechanism of BEN. Highly sensitive, selective, rapid, and fully validated voltammetric methods for the determination of BEN in tablet dosage form were also presented. Under optimized conditions, the peak current showed a linear dependence with concentration in the range between 3.25 μg mL(-1) and 54.20 μg mL(-1) for GC and 1.08 μg mL(-1) and 54.20 μg mL(-1) for BDD electrodes by using differential pulse (DPV) and square wave (SWV) voltammetric techniques. In this study, acid dissociation constant (pK(a)) value of BEN was determined by using the dependence of the retention factor on the pH of the mobile phase using reverse phase-liquid chromatographic (RP-LC) method. The effect of the composition of the mobile phase on the ionization constant was studied by measuring the pK(a) at different acetonitrile-water mixtures, ranging between 50 and 65% (v/v). Also simple, accurate, precise and fully validated RP-LC method for the assay of BEN in dosage form has been developed. XTerra RP-18 column at 25 °C with the mobile phase of acetonitrile:water 55:45 (v/v) adjusted to pH 3.0 with 15 mM o-phosphoric acid was used. Isocratic elution was performed in less than 5.0 min with a flow rate of 1.0 mL min(-1). The RP-LC method allowed quantitation over the 0.25-15.00 μg mL(-1) range for BEN. The proposed voltammetric and RP-LC methods allow a number of cost and time saving benefits. BEN was also exposed to thermal, photolytic, oxidative stress, acid-base catalyzed hydrolyses, and the stressed samples were detected by the proposed RP-LC method.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20801368,

title = {Determination of pK(a) values of some antihypertensive drugs by liquid chromatography and simultaneous assay of lercanidipine and enalapril in their binary mixtures},

author = {Mehmet Gumustas and Senem Sanlı and Nurullah Sanli and Sibel A Ozkan},

doi = {10.1016/j.talanta.2010.07.037},

issn = {1873-3573},

year  = {2010},

date = {2010-09-01},

journal = {Talanta},

volume = {82},

number = {4},

pages = {1528--1537},

abstract = {In this study, pK(a) values were determined using the dependence of the retention factor on the pH of the mobile phase for three ionizable substances, namely, enalapril, lercanidipine and ramipril (IS). The effect of the mobile phase composition on the ionization constant was studied by measuring the pK(a) at different methanol-water mixtures, ranging between 50 and 65% (v/v), using LC-DAD method. Two simple, accurate, precise and fully validated analytical methods for the simultaneous determination of enalapril and lercanidipine in combined dosage forms have been developed. Separation was performed on an X-Terra RP-18 column (250 mm x 4.60mm ID x 5 microm) at 40 degrees C with the mobile phase of methanol-water 55:45 (v/v) adjusted to pH 2.7 with 15 mM orthophosphoric acid. Isocratic elution was performed in less than 12 min with a flow rate of 1.2 mL min(-1). Good sensitivity for the analytes was observed with DAD detection. The LC method allowed quantitation over the 0.50-20.00 microg mL(-1) range for enalapril and lercanidipine. The second method depends on first derivative of the ratio-spectra by measurements of the amplitudes at 219.7 nm for enalapril and 233.0 nm for lercanidipine. Calibration graphs were established for 1-20 microg mL(-1) for enalapril and 1-16 microg mL(-1) lercanidipine, using first derivative of the ratio spectrophotometric method. Both methods have been extensively validated. These methods allow a number of cost and time saving benefits. The described methods can be readily utilized for analysis of pharmaceutical formulations. The methods have been applied, without any interference from excipients, for the simultaneous determination of these compounds in tablets. There was no significant difference between the performance of the proposed methods regarding the mean values and standard deviations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20685469,

title = {Electroanalytical characteristics of antipsychotic drug ziprasidone and its determination in pharmaceuticals and serum samples on solid electrodes},

author = {Dilek Kul and Mehmet Gumustas and Bengi Uslu and Sibel A Ozkan},

doi = {10.1016/j.talanta.2010.04.036},

issn = {1873-3573},

year  = {2010},

date = {2010-06-01},

journal = {Talanta},

volume = {82},

number = {1},

pages = {286--295},

abstract = {Ziprasidone is a psychotropic agent used for the treatment of schizophrenia. Its oxidation was investigated electrochemically at boron-doped diamond and glassy carbon electrodes using cyclic, differential pulse, and square wave voltammetry. The dependence of the peak current and peak potentials on pH, concentration, nature of the buffer, and scan rate were examined. The process was diffusion and adsorption controlled for boron-doped diamond and glassy carbon electrodes, respectively. The possible mechanism of oxidation was discussed with some model compounds that have indole and piperazine oxidations. A linear response was obtained between 8 x 10(-7) and 8 x 10(-5) M for the first peak in acetate buffer (pH 5.5) and between 2 x 10(-6) and 2 x 10(-4) M for the second peak in 0.1 M H(2)SO(4) with boron-doped diamond electrode for differential pulse and square wave voltammetric techniques. The reproducibility and accuracy of the proposed methods were found between 0.31 and 1.20, 99.27 and 100.22, respectively. The recovery studies were also achieved to check selectivity and accuracy of the methods. The proposed methods were applied for the determination of ziprasidone from pharmaceutical dosage forms and human serum samples without any time-consuming extraction, separation, evaporation or adsorption steps prior to drug assay except precipitation of the proteins using acetonitrile. The results were statistically compared with those obtained through an established LC-UV technique, no significant differences were been found between the voltammetric and LC methods.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19998025,

title = {Electrochemical evaluation and determination of antiretroviral drug fosamprenavir using boron-doped diamond and glassy carbon electrodes},

author = {Mehmet Gumustas and Sibel A Ozkan},

doi = {10.1007/s00216-009-3334-3},

issn = {1618-2650},

year  = {2010},

date = {2010-05-01},

journal = {Anal Bioanal Chem},

volume = {397},

number = {1},

pages = {189--203},

abstract = {Fosamprenavir is a pro-drug of the antiretroviral protease inhibitor amprenavir and is oxidizable at solid electrodes. The anodic oxidation behavior of fosamprenavir was investigated using cyclic and linear sweep voltammetry at boron-doped diamond and glassy carbon electrodes. In cyclic voltammetry, depending on pH values, fosamprenavir showed one sharp irreversible oxidation peak or wave depending on the working electrode. The mechanism of the oxidation process was discussed. The voltammetric study of some model compounds allowed elucidation of the possible oxidation mechanism of fosamprenavir. The aim of this study was to determine fosamprenavir levels in pharmaceutical formulations and biological samples by means of electrochemical methods. Using the sharp oxidation response, two voltammetric methods were described for the determination of fosamprenavir by differential pulse and square-wave voltammetry at the boron-doped diamond and glassy carbon electrodes. These two voltammetric techniques are 0.1 M H(2)SO(4) and phosphate buffer at pH 2.0 which allow quantitation over a 4 x 10(-6) to 8 x 10(-5) M range using boron-doped diamond and a 1 x 10(-5) to 1 x 10(-4) M range using glassy carbon electrodes, respectively, in supporting electrolyte. All necessary validation parameters were investigated and calculated. These methods were successfully applied for the analysis of fosamprenavir pharmaceutical dosage forms, human serum and urine samples. The standard addition method was used in biological media using boron-doped diamond electrode. No electroactive interferences from the tablet excipients or endogenous substances from biological material were found. The results were statistically compared with those obtained through an established HPLC-UV technique; no significant differences were found between the voltammetric and HPLC methods.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}