Day 2 :
Keynote Forum
Marika Kamberi
Abbott Vascular, Inc, USA
Keynote: Analytical Challenges in Method Development for Drug Eluting Stents
Time : 10:00-10:45
Biography:
Abstract:
- Kamberi M and Rapoza R (2016) Stability testing of drug-eluting stents (DES). J. Drug Deliver Sci. Technol. 35:58–68.
- Kamberi M and Tran T N (2012) UV-visible spectroscopy as an alternative to liquid chromatography for determination of everolimus in surfactant-containing dissolution media: A useful approach based on solid-phase extraction. J Pharm Biomed Anal 70:94–100.
- Kamberi M (2009) A novel accelerated in-vitro release assay for biodegradable coating of everolimus drug eluting stent: Insight to the drug release mechanisms. Eur J Pharm Sci. 37:217–22.
- Kamberi M, Fu K, Lu J, Chemali M and Feder D (2007) A high-throughput, highly sensitive, HPLC assay for the simultaneous determination of everolimus and clobetasol. J Chromatogr Sci 46:23–29.
- Kamberia M, Garcia H, Federa D P and Rapoza R J (2011) Setting acceptance criteria for validation of analytical methods of drug eluting stents: Minimum requirements for analytical variability. Eur. J Pharm Sci. 42:230–37.
Keynote Forum
Ravi Bhushan
Indian Institute of Technology Roorkee, India
Keynote: Liquid Chromatography for Enantiomeric Purity of Chiral Pharmaceuticals
Time : 10:45-11:30
Biography:
Ravi Bhushan has an expertise in “Enantiomeric resolution of compounds of pharmaceutical importance using liquid chromatography”. So far, he has guided 28 doctoral and 50 masters’ theses, published more than 230 research papers in international refereed journals and chapters in books and encyclopedia. He edited
four Special Issues of Biomedical Chromatography on chiral resolutions as Guest Editor. He received Alexander von Humboldt fellowship of Germany in 1988, and European Economic Community Fellowship in 1992. He is an elected Fellow of the Royal Society of Chemistry, London, and Fellow of National Academy of Sciences India, (FNASc). He received ‘Outstanding Teacher Award’ of the year 2007 at IIT Roorkee, and Khosla Research Prize and Silver Medal of University of Roorkee. His current research interest includes enantioseparation with both achiral phases of chromatography in the absence of any external chiral species.
Abstract:
Development of reliable analytical methods for determination of enantiomers has always been increasing in the fields of chromatography, pharmacology, medicine, asymmetric synthesis, mechanistic studies, extra-terrestrial chemistry, life sciences etc. And, still separation of enantiomers and determination of their purity is challenging and important. With the most infamous example of thalidomide as an enantiomeric drug having unwanted side eff ects in the background the regulatory agencies in the US, Japan and EC and certain other countries insist on registration of single enantiomer of a new drug and ask the pharmaceutical companies to present full information on the stereochemistry and stereoselectivity of both the enantiomers including the necessary stereoselective analytical methods because there exist potential differences between pharmacodynamics and pharmacokinetics of the enantiomers of racemic drugs. Yet, with “a few” exceptions, chiral synthetic racemic drugs are being approved for marketing and pharmaceutical applications, of course, with the appropriate demonstration and justification. Th is presentation covers some aspects of stereochemistry of the drugs that are marketed and administered as racemic mixtures with an emphasis on current status of analytical chemistry methods for enantioseparation and control of enantiomeric purity. Th ere is also a brief discussion on related historical knowledge keeping in view that today we know that the number of pharmacologically active substances produced by nature is large, and the spectrum of biological activities of natural products is extraordinarily broad. Th ere is a discussion on various methods developed primarily at our laboratory for chromatographic resolution of racemates of several pharmaceuticals (e.g., -blockers, NSAIDS, anta-acids, DL-amino acids, Bupropion, Baclofen, Etodolac, Carnitine, and Mexiletine). Included among them are, (i) a de novo approach/method of mixing the chiral selector with the silica gel while making the TLC plates, it is a less exploited area that has great potential; (ii) Separation under both achiral phases in TLC as well as HPLC but using either a simple enantiomerically pure L-amino acid or a chiral ligand exchange reagent in sample preparation; (iii) Indirect approach of enantioseparation. Th ere were synthesized and characterized several new chiral derivatizing reagents (CDRs) capable of detecting diff erent drug enantiomers at nano and pico molar level. To ensure the success of diastereomeric synthesis and the reliability of enantioseparation the configuration of diastereomers so separated was established in our recent studies particularly because most of the time diastereomer corresponding to pure enantiomer of the analyte is not available. As the first report in literature, we developed methods for establishing molecular dissymmetry and determining absolute confi guration of diastereomers, so separated, (and thus the enantiomers) of (RS)-Baclofen, (RS)-Betaxolol, (RS)-propranolol, (RS)-metoprolol and (RS)-atenolol with supplementing application of TLC, HPLC, 1H NMR, LCMS, and the soft ware based on density functional theory (using the Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6-31G* basis set). The methods are of signifi cant importance to pharmaceutical industry and analytical laboratories for determination and control of enantiomeric purity of a variety of drugs.
Keynote Forum
Ebru TÜRKÖZ ACAR
Yeditepe University, Turkey
Keynote: Development and validation of an HPLC method for determination of the eplerenone in rat plasma
Time : 0
Biography:
Ebru Türköz Acar has completed her PhD at Ondokuz Mayis University, Science and Art Faculty, Turkey. She is a Researcher and Lecturer at Yeditepe University, Faculty of Pharmacy Department of Analytical Chemistry.
Abstract:
Eplerenone (EP) is an antihypertensive agent in the pharmacological group of selective aldosterone receptor antagonists (SARAs). Th e chemical structure of EP is pregn-4-ene-7,21-dicarboxylic acid, 9,11 –epoxy-17-hydroxy-3-oxo, γ-lactone methyl ester (7α, 11α, 17α). EP is slightly soluble in water and its solubility is independent from pH. Low water soluble active agents could not off er an eff ective therapy for the patients. To overcome bioavailability problems related to this property, there are some alternative ways like chemical and polymorphic modifi cations of drugs or designing appropriate pharmaceutical dosage forms. To provide an eff ective treatment, colloidal drug carrier systems of EP were prepared in this study. Investigation of loading capacity and encapsulation effi ciency of these carriers and in vitro drug release profi les, in vivo evaluation offormulations, was highly depend on a reliable quantitative analytical method. Th ere are a few methods for the quantitative
determination of EP. Th ese methods mostly include expensive instruments such as LC–MS, but one exception using high
performance liquid chromatography (HPLC) with UV detection was found., To assess in vivo performance of EP formulations
in rats, the method was not suffi cient to provide specifi city. Th us, a new specifi c method for EP detection was needed by using
the simple extraction and detection techniques. To achieve the quantifi cation of EP in the rat plasma, an HPLC method was
developed and validated. EP spiked rat plasma samples were used for validation step. Th en, spiked plasma was extracted and
analyzed. Th e developed method was used to monitor the kinetic study results.
Keynote Forum
Kamal Matar
Kuwait University, Kuwait
Keynote: Therapeutic drug monitoring of busulfan by UPLC-tandem mass spectrometry
Time : 0
Biography:
Kamal Matar is an Associate Professor and Chairman of the Department of Pharmacology & Therapeutics at Kuwait University. He is also a Director of Therapeutic Drug Monitoring & Clinical Toxicology (TDM&CT) Unit, Faculty of Medicine, Kuwait University. He is involved in training Graduate students as well as Resident Physicians in the utilization of a wide variety of analytical techniques used for TDM. He completed his PhD at Cardiff University, UK, in 2000. He has published over 40 peer-reviewed articles and over 30 abstracts in international conferences. He is serving as a Reviewer for some international journals such as: Journal of Chromatography B, Journal of Pharmaceutical & Biomedical Analysis, Medical Principles & Practice, Chemotherapy, Drugs, Analytical Chemistry Insights and Journal of Antimicrobial Chemotherapy. He is a member of International Association of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT).
Abstract:
Background: Busulfan (Bu) is an alkylating agent commonly used in preparative regimens for patients undergoing hematopoietic stem cell transplantation (HSCT) for various types of malignancies. A rapid, selective, reliable, precise, accurate, and reproducible method for quantifi cation of Bu in human plasma using Acquity UPLC system coupled to triple quadrupole tandem mass detector (TQD) has been developed and validated to be used routinely for TDM of Bu employing Busulfan-d8 as an internal standard (IS).
Methods: Th e drug and IS were extracted by ether and analyzed on Acquity UPLC BEH C18 column (2.1x50 mm, 1.7 μm). Quantitation was achieved using positive electrospray ion source (ESI+) interface employing MRM mode.
Results: Th e method was validated over the concentration range of 25–2000 ng/ml (r>0.99). Intra- and inter-run precision of Bu assay at four concentrations (50, 500, 1250 and 1750 ng/ml) ranged from 1.2 to 6.5% with accuracy (bias) varied from –10.7 to –0.2% indicating good precision and accuracy. Stability of Bu in human plasma samples at diff erent conditions showed that the drug was stable under the studied conditions.
Conclusion: The suitability of the developed method for routine TDM was demonstrated by measuring Bu in human plasma samples of patients under preparative and conditioning regimens who will undergo hematopoietic cell transplantation (HCT) for various malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) as well as nonmalignancy conditions such as thalassemias.
Keynote Forum
Dušan Berek
Polymer Institute - SAS, Slovakia
Keynote: Progress in liquid chromatography of synthetic polymers
Time : 0
Biography:
Dusan Berek is working at Polymer Institute, Slovak Academy of Sciences in Bratislava. He served as elected member of the Presidium of the Slovak Academy of Sciences, President of the Slovak Chemical Society, Chairman of the Czecho-Slovak and Slovak National Committee of Chemistry for IUPAC. He is an author and co-author of two monographs and 250+ scientifi c papers published in refereed periodicals, proceedings and chapters of books.
Abstract:
High performance liquid chromatographic (HPLC) methods represent the most important tool for molecular characterization of synthetic polymers. Mean molar masses and molar mass distributions of linear and branched homopolymers are easily determined by size exclusion/gel permeation chromatography (SEC/GPC). As by-products, several other useful data can be assessed with SEC/GPC. Recent progress in SEC/GPC comprises improved instrumental hardware and data processing procedures. High sample throughput of the ultra-fast SEC/GPC allows acceleration of analyses, which is especially important in combinatorial material chemistry and in production control. Still, further improvements of the SEC/GPC method are needed, which include its hardware, especially columns and detectors, and also standardization of sample preparation, measurements, and data processing. SEC/GPC exhibits excellent intra-laboratory repeatability, which evokes a notion of its high reliability. Recent series of the round robin tests, however, revealed surprisingly poor inter-laboratory reproducibility of results. Evidently, accuracy of many SEC/GPC results may be rather limited. In most cases, SEC/GPC does not enable precise molecular characterization of complex polymer systems, which possess more than one distribution in their molecular characteristics. Typically, polymer mixtures, copolymers and functional polymers exhibit besides molar mass distribution also distribution in their chemical structure while e.g. stereo-regular polymer species show also molecular architecture distribution. To assess above distributions, new HPLC procedures are developed. Th ese are based on the controlled combinations of entropic (exclusion) and enthalpic (interaction) retention mechanisms within the same HPLC column or in a series of independent separation systems. Th ese approaches are denoted as “coupled polymer HPLC” and “two-, or multi-dimensional polymer
HPLC”, respectively. Enthalpic retention mechanisms in HPLC of synthetic polymers include adsorption, partition, phase separation and ionic eff ects. We shall review recent progress and also problems in SEC/GPC, as well as in coupled and twodimensional polymer HPLC procedures, and outline anticipated future developments in these fields.
Keynote Forum
Marco Ruijken
MsMetrix, Netherlands
Keynote: All ion differential analysis in product control applications using comprehensive GCxGC/MS
Time : 0
Biography:
Marco Ruijken is the Owner/ Head of Research of MsMetrix, Maarssen the Netherlands. MsMetrix develops informatics solutions for LC/MS and GC/MS Data Analysis in the area of: Metabolite Profi ling, Metabolomics, Proteomics, BioMarker Discovery, and Impurity / Degradation Profi ling. Our mission is to be the premier provider of fast, affordable, user-friendly and reliable software in the above application fi elds. His educational background is in Chemometrics/Statistics and Processing of complex data. Current research topics are advanced deconvolution in GC/MS and GCxGC/MS with the focus on Differential Analysis. Furthermore, we are specialized in implementing ideas or requirements from universities or companies into our existing software tools.
Abstract:
Many applications in comprehensive GCxGC/MS relate to fi nding diff erences between a newly measured sample and a so-called reference sample. Th ese questions may typically arise in application areas like product control or during trouble shooting. Examples are: what are the new impurities present in a new batch compared to a reference batch?; why does this product behave diff erently compared to our reference batch? And; the comparison of samples in food fraud applications to detect illegally added substances. Typically for the above examples is the limited time available to solve these problems. Furthermore, most of the time only a few samples are available, which excludes the use of statistical comparison tools as applied in the fi eld of metabolomics. Although GCxGC-MS has become an invaluable laboratory analysis tool, the procedure may produce gigabytes of data per sample in four dimensions, which makes data analysis time consuming and complicated. In the presentation, new methods and soft ware tools will be presented to quickly fi nd diff erential components from a comparison between two samples only. Certainly, comprehensive GCxGC/MS is a technique having superior separation capabilities
compared to 1-dimensional GC/MS, but co-elution or near co-elution still might occur, especially in complicated matrices.
Whereas most soft ware tools for GCxGC/MS use processing of “TIC” data only, our new methods apply data analysis using
the “all ions” approach. Th e implemented method allows for the detection and de-convolution of diff erential components
that are not or badly separated, even in two dimensions. It will be demonstrated that processing using the “all ion” approach
will substantially detect more (diff erential) components, compared to the analysis using TIC data only. Technical details of
the algorithms will be explained and examples will be given from applications like food analysis, product control in fl avor &
fragrance industry and from base chemistry industry.
Keynote Forum
Katsuhiro Maeda
Kanazawa University, Japan
Keynote: Enantioseparation on optically active poly(diphenylacetylene)s as chiral stationary phases for HPLC
Time : 0
Biography:
Katsuhiro Maeda completed his BS in 1993, MS in 1995, and PhD in 1998 at Nagoya University. In 1998, he joined the Graduate School of Molecular Design and Engineering at Nagoya University as an Assistant Professor and was promoted to Associate Professor in 2002. He moved to Kanazawa University in 2008 and was appointed as a full Professor in 2015. He has published more than 80 original papers.
Abstract:
Enantioseparation by high performance liquid chromatography (HPLC) is recognized as one of the most popular and eff ective methods for both analyzing the composition of enantiomeric mixtures and obtaining pure enantiomers, and a large number of chiral stationary phases (CSPs) have been developed to resolve various racemates. Several optically active helical poly(phenylacetylene)s bearing polar functional groups as a chiral recognition site have been reported to exhibit good chiral recognition abilities toward some racemates due to the preferred-handed helical conformation when used as CSPs for HPLC. On the other hand, the number of optically active poly(diphenylacetylene)s bearing polar functional groups reported so far is very limited and poly(diphenylacetylene)-based CSPs have not yet been reported. In this study, we synthesized optically active poly(diphenylacetylene) derivatives bearing amide groups as eff ective chiral recognition sites by the macromolecular reaction of the optically inactive precursor poly(diphenylacetylene)s bearing carboxy groups with optically active amines and investigated their chiral recognition abilities as CSPs for HPLC. Th e obtained polymers showed good chiral recognition ability towards diverse racemates when used as CSPs for HPLC. Notably, the preferred-handed helical conformation was induced on the polymer backbone by the thermal annealing process, which was applied aft er the introduction of the optically active pendants via a polymer reaction. Th e chiral recognition abilities of the polymers with a preferred-handed helicity were greater than those of the as-prepared polymers without a preferred-handed helicity. Th ese results indicated that the macromolecular
helicity induced in the polymer backbone by thermal annealing as a consequence of the eff ect of the chiral pendant groups was playing an important role in the high chiral recognition ability of these poly(diphenylacetylene) derivatives.
Keynote Forum
Dusan Berek
Polymer Institute, Slovak Academy of Sciences, Slovakia
Keynote: Progress in liquid chromatography of synthetic polymers
Time : 12:45-13:15
Biography:
Abstract:
Keynote Forum
Katsuhiro Maeda
Kanazawa University, Japan
Keynote: Enantioseparation on optically active poly(diphenylacetylene)s as chiral stationary phases for HPLC
Time : 15:15-15:45
Biography:
Abstract:
Keynote Forum
Marco Ruijken
MsMetrix, The Netherlands
Keynote: All Ion Differential Analysis in Product Control Applications using Comprehensive GCxGC/MS
Time : 14:15-14:45
Biography:
Abstract:
Keynote Forum
Hermes Licea Perez
Pennsylvania,United States
Keynote: Applications of Supercritical Fluid Chromatography (SFC) for Chiral Metabolite Separations in DMPK Environment
Time : 11:00-11:30AM
Biography:
Abstract:
Keynote Forum
Marco Ruijken
MsMetrix, The Netherlands
Keynote: All Ion Differential Analysis in Product Control Applications using Comprehensive GCxGC/MS
Time : 12:00-12:30PM
Biography:
Marco Ruijken has his experience in chemometrics and chromatography data analysis. New methods and techniques are applied to different fields in chromatography to enhance information content and speed of analysis. His special attention has the implementation of advanced methods and techniques in routine analysis without the need for being highly educated or trained.
Abstract:
Keynote Forum
Aleš Štrancar
BIA Separations, Slovenia
Keynote: Chromatographic separation of full and empty AAV8 capsids
Time : 9
Biography:
Abstract:
Keynote Forum
S. Peljhan
BIA Separations, Slovenia
Keynote: PATfixTM - At-line monitoring of impurities and critical quality attributes in biopharmaceutical up-and downstream processes using HPLC fingerprinting
Time : 0
Biography:
Abstract:
Biography:
Abstract:
Keynote Forum
Ashraf Ali
Inha University, South Korea
Keynote: Polystyrene bound silica monolith particles as HPLC stationary phase of excellent separation efficiency
Time : 0
Biography:
Abstract:
Keynote Forum
Danijela AÅ¡perger
University of Zagreb, Croatia
Keynote: Chromatographic monitoring of febantel after biodegradation and advanced oxidation processes
Time : 0
Biography:
Abstract:
Keynote Forum
Deming Song
Food and Drug Administration, USA
Keynote: Determination of Ochratoxin A in Food Samples by Liquid Chromatography/Electrospray Ionization Triple Quadrupole-MS-MS Spectrometry
Time : 0
Biography:
Abstract:
Keynote Forum
Berek D
Polymer Institute,Slovakia
Keynote: Evaluation of high-performance liquid chromatography columns retentivity with help of macromolecular probes
Time : 9
Biography:
Abstract:
Keynote Forum
MarÃa Ramos Payan
Keynote: A effective microfluidic device for the extraction of fluoroquinolones using liquid phase microextraction and its analysis by HPLC
Time : 0
Biography:
Abstract:
Keynote Forum
Felix Anyakudo
Farmaceutische Analyse, Belgium
Keynote: Analysis of chlorinated compounds, phenolic compounds, styrenes, indene, dicyclopentadiene, dihydrocyclopentadiene, cumene, benzene, toluene, ethylbenzene and xylenes in fuel oil by headspace GC-MS
Time : 0
Biography:
Abstract:
Keynote Forum
WU Gang
Zhejiang University, China
Keynote: Determination of 7 nipagin ester preservatives in leather by ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) coupled with gel permeation chromatography (GPC) clean-up
Time : 0
Biography:
Abstract:
Keynote Forum
Giacomo Russo
University of Naples Federico II, Italy
Keynote: Monitoring of bisphenol A and bisphenol S in thermal paper receipts from the Italian market and estimated transdermal human intake: A pilot study
Time : 9
Biography:
Abstract:
Keynote Forum
Han Sol Lee
Chonnam national University, South Korea
Keynote: Quantification of acetamiprid and thiacloprid residues in field-incurred butterbur samples using liquid chromatography-tandem mass spectrometry
Time : 0
Biography:
Abstract:
Keynote Forum
Md. Humayun Kabir
Chonnam National University, South Korea
Keynote: Determination kinetics and pre-harvest residue limit of pyriofenone in oriental melon (Cucumis melon var. makuwa) grown under regulated climatic conditions
Time : 0
Biography:
Abstract:
Keynote Forum
Kahtan J. Hasson
Al-Rasheed University
Keynote: Complexation of Diclofenac Sodium with Hydroxy Propyl Beta-Cyclodextrine Improves its Solublility and Stablility in Ampoule Solution which is Determined by HPLC
Time : 0
Biography:
Abstract:
Keynote Forum
Kamal M. Matar
Kuwait University, Kuwait
Keynote: Therapeutic Drug Monitoring of Busulfan by UPLC-Tandem Mass Spectrometry
Time : 12:15-12:45
Biography:
Abstract:
Keynote Forum
Koichi Tanaka
Kansai University, Japan
Keynote: Efficient HPLC enantiomer separation using novel homochiral metal- organic frameworks as chiral stationary phases
Time : 0
Biography:
Abstract:
Keynote Forum
Zhenli Liu
China Academy of Chinese Medical Sciences, China
Keynote: Application of a strategy based on metabolomics guided promoting blood circulation bioactivity compounds screening of vinegar
Time : 9
Biography:
Abstract:
Keynote Forum
MarÃa Ramos Payan
Instituto de Microelectrónica de Barcelona IMB-CNM (CSIC), Spain
Keynote: Advantages of using a microfludic-chip as sample treatment miniaturization for a subsequent analysis by HPLC
Time : 0
Biography:
Abstract:
Keynote Forum
Marika Kamberi
Santa Clara,USA
Keynote: Analytical Challenges in Method Development for Drug Eluting Stents Marika Kamberi PhD,
Time : 10:00-10:45
Biography:
Dr Kamberi holds a double major in chemical engineering & industrial chemistry. She received her PhD from Oita University in Oita, Japan and completed postdoctoral studies at Stanford University in Palo Alto, California. Dr Kamberi has over 25 years of pharmaceutical experience with increasing levels of responsibility across functional disciplines, including analytical R&D, bioanalytical, pre-clinical research, quality control and stability. She is currently the director of Analytical Chemistry, Bioanalytical, Stability at Abbott Vascular in Santa Clara, California, a worldwide premier medical device organization. Marika is author/co-author of more than 50 papers published in peer-reviewed journals, conference proceedings, and book chapters, and of 10 US patents.
Abstract:
Keynote Forum
Ebru Türköz Acar
Yeditepe University, Turkey
Keynote: Development and Validation of an HPLC Method for Determination of the Eplerenon in Rat Plasma
Time : 11:45-12:15
Biography:
Abstract:
- High Performance Liquid Chromatography | Applications of Chromatography |Advancement in Chromatography
Location: Olimpica 2
Chair
Dusan Berek
Polymer Institute - SAS, Slovakia
Co-Chair
Mellissa Graewert
EMBL Hamburg Outstation, Germany
Session Introduction
Ebru TÜRKÖZ ACAR
Yeditepe University, Turkey
Title: Development and validation of an HPLC method for determination of the eplerenone in rat plasma
Time : 11:45-12:15
Biography:
Ebru Türköz Acar has completed her PhD at Ondokuz Mayis University, Science and Art Faculty, Turkey. She is a Researcher and Lecturer at Yeditepe University, Faculty of Pharmacy Department of Analytical Chemistry.
Abstract:
Eplerenone (EP) is an antihypertensive agent in the pharmacological group of selective aldosterone receptor antagonists (SARAs). Th e chemical structure of EP is pregn-4-ene-7,21-dicarboxylic acid, 9,11 –epoxy-17-hydroxy-3-oxo, γ-lactone methyl ester (7α, 11α, 17α). EP is slightly soluble in water and its solubility is independent from pH. Low water soluble active agents could not off er an eff ective therapy for the patients. To overcome bioavailability problems related to this property, there are some alternative ways like chemical and polymorphic modifi cations of drugs or designing appropriate pharmaceutical dosage forms. To provide an eff ective treatment, colloidal drug carrier systems of EP were prepared in this study. Investigation of loading capacity and encapsulation effi ciency of these carriers and in vitro drug release profi les, in vivo evaluation offormulations, was highly depend on a reliable quantitative analytical method. Th ere are a few methods for the quantitative determination of EP. Th ese methods mostly include expensive instruments such as LC–MS, but one exception using high performance liquid chromatography (HPLC) with UV detection was found., To assess in vivo performance of EP formulations in rats, the method was not suffi cient to provide specifi city. Th us, a new specifi c method for EP detection was needed by using the simple extraction and detection techniques. To achieve the quantifi cation of EP in the rat plasma, an HPLC method was developed and validated. EP spiked rat plasma samples were used for validation step. Then, spiked plasma was extracted and analyzed. The developed method was used to monitor the kinetic study results.
Kamal Matar
Kuwait University, Kuwait
Title: Therapeutic drug monitoring of busulfan by UPLC-tandem mass spectrometry
Time : 12:15-12:45
Biography:
Kamal Matar is an Associate Professor and Chairman of the Department of Pharmacology & Therapeutics at Kuwait University. He is also a Director of Therapeutic Drug Monitoring & Clinical Toxicology (TDM&CT) Unit, Faculty of Medicine, Kuwait University. He is involved in training Graduate students as well as Resident Physicians in the utilization of a wide variety of analytical techniques used for TDM. He completed his PhD at Cardiff University, UK, in 2000. He has published over 40 peer-reviewed articles and over 30 abstracts in international conferences. He is serving as a Reviewer for some international journals such as: Journal of Chromatography B, Journal of Pharmaceutical & Biomedical Analysis, Medical Principles & Practice, Chemotherapy, Drugs, Analytical Chemistry Insights and Journal of Antimicrobial Chemotherapy. He is a member of International Association of Therapeutic Drug Monitoring & Clinical Toxicology (IATDMCT).
Abstract:
Background: Busulfan (Bu) is an alkylating agent commonly used in preparative regimens for patients undergoing hematopoietic stem cell transplantation (HSCT) for various types of malignancies. A rapid, selective, reliable, precise, accurate, and reproducible method for quantifi cation of Bu in human plasma using Acquity UPLC system coupled to triple quadrupole tandem mass detector (TQD) has been developed and validated to be used routinely for TDM of Bu employing Busulfan-d8 as an internal standard (IS).
Methods: Th e drug and IS were extracted by ether and analyzed on Acquity UPLC BEH C18 column (2.1x50 mm, 1.7 μm). Quantitation was achieved using positive electrospray ion source (ESI+) interface employing MRM mode.
Results: Th e method was validated over the concentration range of 25–2000 ng/ml (r>0.99). Intra- and inter-run precision of Bu assay at four concentrations (50, 500, 1250 and 1750 ng/ml) ranged from 1.2 to 6.5% with accuracy (bias) varied from –10.7 to –0.2% indicating good precision and accuracy. Stability of Bu in human plasma samples at diff erent conditions showed that the drug was stable under the studied conditions.
Conclusion: The suitability of the developed method for routine TDM was demonstrated by measuring Bu in human plasma samples of patients under preparative and conditioning regimens who will undergo hematopoietic cell transplantation (HCT) for various malignancies including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) as well as nonmalignancy conditions such as thalassemias.
Dušan Berek
Polymer Institute - SAS, Slovakia
Title: Progress in liquid chromatography of synthetic polymers
Time : 12:45-13:15
Biography:
Dusan Berek is working at Polymer Institute, Slovak Academy of Sciences in Bratislava. He served as elected member of the Presidium of the Slovak Academy of Sciences, President of the Slovak Chemical Society, Chairman of the Czecho-Slovak and Slovak National Committee of Chemistry for IUPAC. He is an author and co-author of two monographs and 250+ scientifi c papers published in refereed periodicals, proceedings and chapters of books.
Abstract:
High performance liquid chromatographic (HPLC) methods represent the most important tool for molecular characterization of synthetic polymers. Mean molar masses and molar mass distributions of linear and branched homopolymers are easily determined by size exclusion/gel permeation chromatography (SEC/GPC). As by-products, several other useful data can be assessed with SEC/GPC. Recent progress in SEC/GPC comprises improved instrumental hardware and data processing procedures. High sample throughput of the ultra-fast SEC/GPC allows acceleration of analyses, which is especially important in combinatorial material chemistry and in production control. Still, further improvements of the SEC/GPC method are needed, which include its hardware, especially columns and detectors, and also standardization of sample preparation, measurements, and data processing. SEC/GPC exhibits excellent intra-laboratory repeatability, which evokes a notion of its high reliability. Recent series of the round robin tests, however, revealed surprisingly poor inter-laboratory reproducibility of results. Evidently, accuracy of many SEC/GPC results may be rather limited. In most cases, SEC/GPC does not enable precise molecular characterization of complex polymer systems, which possess more than one distribution in their molecular characteristics. Typically, polymer mixtures, copolymers and functional polymers exhibit besides molar mass distribution also distribution in their chemical structure while e.g. stereo-regular polymer species show also molecular architecture distribution. To assess above distributions, new HPLC procedures are developed. Th ese are based on the controlled combinations of entropic (exclusion) and enthalpic (interaction) retention mechanisms within the same HPLC column or in a series of independent separation systems. Th ese approaches are denoted as “coupled polymer HPLC” and “two-, or multi-dimensional polymer HPLC”, respectively. Enthalpic retention mechanisms in HPLC of synthetic polymers include adsorption, partition, phase separation and ionic eff ects. We shall review recent progress and also problems in SEC/GPC, as well as in coupled and twodimensional polymer HPLC procedures, and outline anticipated future developments in these fields.
Publications
- Berek D (2016) Critical assessment of “critical” liquid chromatography of block copolymers J. Sep. Sci. 39:93–101.
- Clementi L A, Sišková A, Meira GR, Berek D and Vega J R (2016) Molar mass distributions in binary homopolymer blends by single step two- dimensional liquid chromatography: Operation and data treatment. Polym. Testing 52:33-40.
- Netopilík M, Janata M, Svitáková R, Trhlíková O, Berek D, Macova E, Limpouchová Z and Procházka K (2016) Chromatographic study of the conformational behavior of graft copolymers with a broad distribution of grafting densities in dilute solutions in selective solvents for grafts. J. Liq. Chromatogr. Rel. Technol. 39:50–58.
- Rollet M, Pelletier P B, Altounian A, Berek D, Maria S, Phan T N T and Gigmes D (2015) Separation of parent homopolymers from poly(ethylene oxide) and polystyrene-based block copolymers by liquid chromatography under limiting conditions of desorption – Determination of the suitable molar mass range and optimization of chromatographic conditions. J Chromatogr. A 1392:37-47.
Marco Ruijken
MsMetrix, Netherlands
Title: All ion differential analysis in product control applications using comprehensive GCxGC/MS
Time : 14:15-14:45
Biography:
Marco Ruijken is the Owner/ Head of Research of MsMetrix, Maarssen the Netherlands. MsMetrix develops informatics solutions for LC/MS and GC/MS Data Analysis in the area of: Metabolite Profi ling, Metabolomics, Proteomics, BioMarker Discovery, and Impurity / Degradation Profi ling. Our mission is to be the premier provider of fast, affordable, user-friendly and reliable software in the above application fi elds. His educational background is in Chemometrics/Statistics and Processing of complex data. Current research topics are advanced deconvolution in GC/MS and GCxGC/MS with the focus on Differential Analysis. Furthermore, we are specialized in implementing ideas or requirements from universities or companies into our existing software tools.
Abstract:
Many applications in comprehensive GCxGC/MS relate to fi nding diff erences between a newly measured sample and a so-called reference sample. Th ese questions may typically arise in application areas like product control or during trouble shooting. Examples are: what are the new impurities present in a new batch compared to a reference batch?; why does this product behave diff erently compared to our reference batch? And; the comparison of samples in food fraud applications to detect illegally added substances. Typically for the above examples is the limited time available to solve these problems. Furthermore, most of the time only a few samples are available, which excludes the use of statistical comparison tools as applied in the fi eld of metabolomics. Although GCxGC-MS has become an invaluable laboratory analysis tool, the procedure may produce gigabytes of data per sample in four dimensions, which makes data analysis time consuming and complicated. In the presentation, new methods and soft ware tools will be presented to quickly fi nd diff erential components from a comparison between two samples only. Certainly, comprehensive GCxGC/MS is a technique having superior separation capabilities compared to 1-dimensional GC/MS, but co-elution or near co-elution still might occur, especially in complicated matrices. Whereas most soft ware tools for GCxGC/MS use processing of “TIC” data only, our new methods apply data analysis using the “all ions” approach. The implemented method allows for the detection and de-convolution of diff erential components that are not or badly separated, even in two dimensions. It will be demonstrated that processing using the “all ion” approach will substantially detect more (diff erential) components, compared to the analysis using TIC data only. Technical details of the algorithms will be explained and examples will be given from applications like food analysis, product control in flavor & fragrance industry and from base chemistry industry.
Ravi Bhushan
Indian Institute of Technology Roorkee, India
Title: HPLC enantioseparation of (RS)-Isoprenaline and enhanced detection in human plasma and commercial sample: Establishment of configuration andelution order in the absence of pure isomer
Time : 14:45-15:15
Biography:
Ravi Bhushan has an expertise in “Enantiomeric resolution of compounds of pharmaceutical importance using liquid chromatography”. So far, he has guided 28 doctoral and 50 masters’ theses, published more than 230 research papers in international refereed journals and chapters in books and encyclopedia. He edited four Special Issues of Biomedical Chromatography on chiral resolutions as Guest Editor. He received Alexander von Humboldt fellowship of Germany in 1988, and European Economic Community Fellowship in 1992. He is an elected Fellow of the Royal Society of Chemistry, London, and Fellow of National Academy of Sciences India, (FNASc). He received ‘Outstanding Teacher Award’ of the year 2007 at IIT Roorkee, and Khosla Research Prize and Silver Medal of University of Roorkee. His current research interest includes enantioseparation with both achiral phases of chromatography in the absence of any external chiral species.
Abstract:
There has been an increasing awareness that the two enantiomers of a chiral drug have diff erent pharmaceutical responses in the human body and other living systems. Th erefore, the importance of enantioseparation remains as established and challenging. (RS)-isoprenaline (Ipn) is a non-selective β-adrenergic agonist used in the treatment of bradycardia and heart block. Th e (R)-Ipn is approximately 90 times more potent than its (S)-enantiomer, therefore, determination of enantiomeric purity of this compound is essential for diagnostic purposes and therapeutic drug monitoring. With the above background and lack of literature on the work focused herein, we developed a validated analytical method for separation of enantiomers of (RS)- isoprenaline and pharmaceutical formulations. Ipn contains a reactive amino functional group (only one in close proximity to the stereogenic centers) suitable for quantitative transformation with a functionally compatible chiral reagent. Cyanuric chloride (CC, trichloro-s-triazine) was chosen for its tri-functionality and high molar absorptivity and D-phenyl glycine (D-Phg) was introduced as chiral auxiliary by substitution of one of the Cl atoms in CC. Th e second Cl atom was replaced with piperidinyl moiety as the achiral unit resulting into a structurally new CDR because such a CDR with combination of these two moieties has not yet been reported. Th e CDR was characterized. Diastereomeric derivatives of (RS)-Ipn were synthesized under microwave irradiation when the third Cl atom of CC was substituted. Th e separation of these diastereomeric derivatives was achieved using LiChrospher C18 (IxI.D. 25 cm×4.6 mm, 5 um particle size) column with mobile phase consisting of MeCN and TFA under gradient elution at fl ow rate of 1.0 mL min-1 and UV detection at 254 nm. Th e conditions for synthesis and separation were optimized by extensive experimentation with many variations at diff erent stages. Th e method was successfully applied for detection and separation of enantiomers of (RS)-Ipn in human plasma and from the commercial sample. Limit of detection values were found to be 24.6 and 26.8 ng mL-1 for the two diastereomeric derivatives. Geometry optimized lowest energy structures of diastereomeric derivatives of (RS)-Ipn were developed using a standard Gaussian soft ware program which helped in establishing the confi guration and elution order of the diastereomeric derivatives. Th e method can be used not only for control of enantiomeric purity of Ipn in industrial/commercial samples but also for enantioseparation and determination of other structurally similar pharmaceutically important molecules for routine analysis as well.
Katsuhiro Maeda
Kanazawa University, Japan
Title: Enantioseparation on optically active poly(diphenylacetylene)s as chiral stationary phases for HPLC
Time : 15:15-15:45
Biography:
Katsuhiro Maeda completed his BS in 1993, MS in 1995, and PhD in 1998 at Nagoya University. In 1998, he joined the Graduate School of Molecular Design and Engineering at Nagoya University as an Assistant Professor and was promoted to Associate Professor in 2002. He moved to Kanazawa University in 2008 and was appointed as a full Professor in 2015. He has published more than 80 original papers.
Abstract:
Enantioseparation by high performance liquid chromatography (HPLC) is recognized as one of the most popular and eff ective methods for both analyzing the composition of enantiomeric mixtures and obtaining pure enantiomers, and a large number of chiral stationary phases (CSPs) have been developed to resolve various racemates. Several optically active helical poly(phenylacetylene)s bearing polar functional groups as a chiral recognition site have been reported to exhibit good chiral recognition abilities toward some racemates due to the preferred-handed helical conformation when used as CSPs for HPLC. On the other hand, the number of optically active poly(diphenylacetylene)s bearing polar functional groups reported so far is very limited and poly(diphenylacetylene)-based CSPs have not yet been reported. In this study, we synthesized optically active poly(diphenylacetylene) derivatives bearing amide groups as eff ective chiral recognition sites by the macromolecular reaction of the optically inactive precursor poly(diphenylacetylene)s bearing carboxy groups with optically active amines and investigated their chiral recognition abilities as CSPs for HPLC. The obtained polymers showed good chiral recognition ability towards diverse racemates when used as CSPs for HPLC. Notably, the preferred-handed helical conformation was induced on the polymer backbone by the thermal annealing process, which was applied aft er the introduction of the optically active pendants via a polymer reaction. Th e chiral recognition abilities of the polymers with a preferred-handed helicity were greater than those of the as-prepared polymers without a preferred-handed helicity. These results indicated that the macromolecular helicity induced in the polymer backbone by thermal annealing as a consequence of the eff ect of the chiral pendant groups was playing an important role in the high chiral recognition ability of these poly(diphenylacetylene) derivatives.
Publications
- Maeda K, Maruta M, Sakai Y, Ikai T and Kanoh S (2016) Synthesis of optically active poly(diphenylacetylene)s using polymer reactions and an evaluation of their chiral recognition abilities as chiral stationary phases for HPLC. Molecules 21:1487-1500.
- Maeda K, Maruta M, Shimomura K, Ikai T and Kanoh S (2016) Chiral recognition ability of an optically active poly(diphenylacetylene) as a chiral stationary phase for HPLC. Chem. Lett. 45:1063-1065.
- Yashima E, Ousaka N, Taura D, Shimomura K, Ikai T and Maeda K (2016) Supramolecular helical systems: Helical assemblies of small molecules, foldamers, and polymers with chiral amplification and their functions. Chem. Rev. 116:13752-13990.
- Maeda K, Miyagawa T, Furuko A, Onouchi H and Yashima E (2015) Dual memory of enantiomeric helices in poly(phenylacetylene)s induced by a single enantiomer through helix inversion and dual storage of the enantiomeric helicity memories. Macromolecules 48:4281-4293.
- Shimomura K, Ikai T, Kanoh S, Yashima E and Maeda K (2014) Switchable enantioseparation based on macromolecular memory of a helical poly-acetylene in the solid state. Nat. Chem. 6:429-434.