Day 1 :
Keynote Forum
Imeda Rubashvili
Ivane Javakhishvili Tbilisi State University, Georgia
Keynote: Development and Validation of Sampling Procedures and Quantitative Determination HPLC Methods of Active Pharmaceutical Ingredient - Alprazolam Residues on Pharmaceutical Technological Equipment
Biography:
Imeda Rubashvili, PhD, senior scientific researcher at Ivane Javakhishvili Tbilisi State University and the head of validation department of pharmaceutical company “Aversi-Rational” Ltd. He has published more than 30 scientific papers. He is the member of the council of young scientists of the Georgian National Academy of Sciences.
Abstract:
Cleaning validation is a critical process of quality assurance system which must be confirmed documentary and clearly the effectiveness of cleaning procedure after pharmaceutical product manufacturing. Cross-contamination causes a risk to impact patient safety, reduces drug effectiveness, causes undesirable “strange side effect” and, in the worst case the result of the consumption of drug will be lethal. To solve this analytical problem is difficult and requires consecutive and well-planed scientific investigations. The problem is important, particularly, in case of high potent, toxic, hard removing from surfaces and practically insoluble active pharmaceutical ingredients. Cleaning validation is complex scientific work including the development and validation of sampling procedures of active pharmaceutical ingredients residues on pharmaceutical equipment surfaces and their quantitative determination of residues in the collected samples from surfaces. Also, quantitative analysis needs an effective, selective and specific analytical method. The aim of this study was to validate direct - swab and indirect - rinse sampling procedures and demonstrate the applicability of developed HPLC method for quantitative estimation of residues of active pharmaceutical ingredient - alprazolam residues as a high potent and practically insoluble compound in water in cleaning control samples collected from pharmaceutical equipment surfaces after manufacturing of alprazolam 1 mg uncoated tablets. The swab and rinse sampling procedures were developed in order to obtain a suitable and good recovery (>90 %). The sampling procedures were qualified in respect to the validation parameters. The known amounts of alprazolam at three different concentration levels are spiked onto representative surfaces, which are disinfected and cleaned, then dried, sampled using swabbing and rinsing and analyzed using the validated HPLC method. Additionally, the robustness of sampling procedures was assessed. For swab sampling the surface (sampling area - 25 cm2 ) was successively wiped with one micro polyester swab (3×2.5×10 mm) moistened with diluent – methanol. The influence of swab material on quantitative determination of alprazolam was checked as well.
The method for quantitative determination of alprazolam residues was developed using LC system “Ag 1260 Infinity” and Prodigy C8(2) 250 × 4.0 mm, 5 µm column with a mobile phase - a mixture of methanol, phosphate buffer pH 3.0 and acetonitrile (10 : 45 : 45 v/v); The flow rate – 1.4 mL/min; The detector wavelength - 220 nm; The injection volume – 20 μL; The column temperature – 300 C. The method was validated with respect to robustness, system suitability test, specificity, linearity-range, accuracy, precision (intra-day and inter day), limit of detection (LOD) and quantitation (LOQ). The stability of alprazolam sample solutions and 0.45 µm membrane filter compatibility were studied as well. These studies were performed in accordance with established ICH Q2 guideline and USP requirements. The calibration curve is linear (r2 =1.00000) over a wide concentration range 0.0075 – 10 µg/mL; LOQ - 0.0075 µg/mL and LOD - 0.005 µg/mL. The method can be applied to determine quantitatively alprazolam residues in test solutions with very low concentrations below the acceptable concentration of the cross-contamination limit.
- Newly Emerging Drugs, Alzheimer’s Disease, Biochemistry of Diabetes
Location: Webinar
Chair
Imeda Rubashvili
Ivane Javakhishvili Tbilisi State University
Session Introduction
Prakash.M.M.S Kinthada
Jawahar Lal Technological University Anantapur, India
Title: Transition metal complexes/organometallic compounds as anticancer/anti HIV drugs or in pharmaceutical industry
Biography:
I am Prof.Dr.Prakash.M.M.S Kinthada, a Professor in the Department Of Chemistry at Sri Vidyanikethan Engineering college,Jawahar Lal Technological University,Anantapur,A.Rangam Peta, Tirupathi,INDIA.Earlier I was an AssociateProfessor in Chemistry ,GIT,GITAM University, Visakhapatnam, INDIA. Ihave recently returned from USA, where I was a NIH visiting fellow atKARMONAS CANCER RESEARCHINSTITUTE, Wayne State University School OfMedicine. Earlier I was a Royal Society Visiting Scientist in theInorganic chemistry laboratories at the University of Oxford,UK, working on" Transition metal complexes as Anticancer Drugs".Earlier I was a visiting fellow at the Department of ChemicalEngineering and Applied Chemistry at Aston University, Birmingham.Prior to that I was a Nehru Centenary British Council Fellow in theorganometallic laboratories at Imperial college of Science, Technologyand Medicine, London, UK. Prior to that I was a CSIR Researchassociate in the Organometallic laboratories, Department of chemistry,INDIAN INSTITUTE OF TECHNOLOGY,NEWDELHI,INDIA. I have published allmy research in high impact international journals and Presented papersin International Conferences including American Chemical societyConferences.I have published 33 International publications and 31international conference presentations including American ChemicalSociety conferences.
Abstract:
Cancer is a dreadful disease and any practical solution in combating this disease is of paramount importance to public health. Cancer patients have burdened by drug induced toxic side effects, and no turned to seek help from the complementary and alternative medicine hoping for a better cure. Research on Platinum based drugs and Non Platinum based drugs is a Multi-Million Dollar Industry in USA and there is every need to produce safe drugs for the cure of this monstrous disease. Flavonoids have a long history of use in traditional medicines in many cultures. The phytochemical, curcumin is one of the major dietary flavonoid, belonging to a group of flavonol, Curcumin is a natural polyphenol. It is highly potential molecule capable of preventing and treating various cancers. Various dietary chemo preventive agents, turmeric powder or its extract are broadly used as therapeutic preparations in Indian System of medicine. We provide a summarized synthesis and structural determination of Curcumin Oxime, Curcumin Thiosemicarbazone derivative of Gold (III) complex. The use of these analogs for prevention of cancer tumor progression and treatments of human malignancies. A pharmacologic agent for treating and/or preventing cancer, among other diseases and conditions, and particularly breast, prostate, and pancreatic cancer, in humans and animals. The novel pharmacologic agent is an isoflavonoid or isoflavonoid mimetic covalently attached to a cytotoxic pharmacophore that, preferably has the ability to conjugate with a metal salt to form a more potent metal complex, particularly a Au (III) complex and other complexes of Platinum, Palladium, Ruthenium, Copper etc.
Dong-Jun Fu
University of California Irvine, USA
Title: Design and synthesis of formononetin-dithiocarbamate hybrids that inhibit growth and migration of PC-3 cells via MAPK/Wnt signaling pathways
Biography:
Novel formononetin-dithiocarbamate derivatives were designed, synthesized and evaluated for antiproliferative activity against three selected cancer cell line (MGC-803, EC-109, PC-3). The first structure-activity relationship (SAR) for this formononetin-dithiocarbamate scaffold is explored with evaluation of 14 variants of the structural class. Among these analogues, tert-butyl-4-(((3-((3-(4-methoxyphenyl)-4-oxo-4H-chromen-7-yl)oxy)propyl)thio)carbonothioyl)piperazine-1-carboxylate (8i) showed the best inhibitory activity against PC-3 cells (IC50 = 1.97 μM). Cellular mechanism studies elucidated 8i arrests cell cycle at G1 phase and regulates the expression of G1 checkpoint-related proteins in concentration-dependent manners. Furthermore, 8i could inhibit cell growth via MAPK signaling pathway and inhibit migration via Wnt pathway in PC-3 cells.
Abstract:
Dong-Jun Fu was born in 1990 in Henan province, P. R. of China. He is currently pursuing his joint Ph.D. at Zhengzhou University and university of California, Irvine majoring in medicinal chemistry. His research focuses on the discovery of novel antitumor molecules using modern synthetic strategies, which was supported by China Scholarship Council (CSC). Until now, he has published more than 20 SCI papers and more than 8 patents.
Biography:
There has been substantial progress in the management of patients with osteoporosis and the prevention of osteoporotic fractures. Currently available strong anti-resorptive agents are bisphosphonates and an anti-receptor activator of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral and non-vertebral fractures, their mechanisms of action are different. There are differences in the mechanism of action of these two drugs. Bisphosphonates accumulate on the mineralized bone surface and are released by the acid environment under osteoclastic bone resorption, whereas denosumab is not accumulated on bone but directly binds RANKL and inhibits its binding to the receptor RANK.. As anabolic agents, only teriparatide has been available for a long time, but abaloparatide, a synthetic analog of PTHrP(1–34), is currently under
development. Because of the difference in the preferential binding conformations of PTH1 receptor between teriparatide and abaloparatide, the latter shows anabolic effects with fewer bone resorptive effects. Romosozumab, an anti-sclerostin antibody, inhibits the action of sclerostin,. Romosozumab robustly increases vertebral and proximal femoral bone mineral density within 12 months and inhibits vertebral and clinical fractures in patients with osteoporosis by enhancing bone formation and inhibiting bone resorption. In my talk I shall summarize the recent advances in therapeutic agents for the treatment of osteoporosis and discuss future prospects with their use.
Abstract:
Dr Suzan Darwish has completed her BPharm, MSc from faculty of Pharmacy, Alexandria University, Egypt; PhD in Pharmacology from Strathclyde University,UK. Acted as Professor of Pharmacology in Faculty of Medicine, University of Alexandria, Egypt, from 1988 until 2003.then acted as head of the same department until 2005. She is now Emeritus Professor in Pharmacology, Faculty of Medicine, Alexandria University, since 2005 .
Published 35 papers in reputed journals and supervised 14 MSc/ PhD thesis Elected as president of the Egyption Association of the Advancement of Basic Medical Sciences ( EAMBS) from 2003 up till now.
Suhair Mansour Jambi
University of Jeddad, Saudi Arabia
Title: Dr Suzan Darwish has completed her BPharm, MSc from faculty of Pharmacy, Alexandria University, Egypt; PhD in Pharmacology from Strathclyde University,UK. Acted as Professor of Pharmacology in Faculty of Medicine, University of Alexandria, Egypt, from 1988 until 2003.then acted as head of the same department until 2005. She is now Emeritus Professor in Pharmacology, Faculty of Medicine, Alexandria University, since 2005 . Published 35 papers in reputed journals and supervised 14 MSc/ PhD thesis Elected as president of the Egyption Association of the Advancement of Basic Medical Sciences ( EAMBS) from 2003 up till now.
Biography:
My name is Suhair Mansour Jambi, I am completed the PhD at 2011 from King AbdulazizUniversity in Saudia Arabia in Jeddah. I am interested of of modern technologies in the field of metallic complexes, the structure of metal complexes using modern methods, thiourea complexes and their use in the treatment of some microbes and some diseases such as cancer, e-learning and the use of modern technologies. I am published more than 10 papers in reputed journal such as Journal of Molecular Liquids, Z. Kristallogr. NCS, Journal of Molecular Structure, Journal of Sulfur Chemistry. Now I work in University of Jeddah.
Abstract:
The new bifunctional ligand N-phenyl-N′- (4′ -methylthiazol -2′-yl)-thiourea (PhMeTzTu) containing the thiourea and the thiazol functions. The ligand and its nickel (II) Platinum (II) and Palladium (II) complexes were synthesized and characterized by elemental analyses, molar conductivities, magnetic susceptibilities, IR, UV- vis, 1H, 13C NMR and mass spectra. The IR spectra and The 1H, 13C NMR indicate that the ligand behaves as neutral monodendate or bidendate towards Ni(II) ), Pd(II) and Pt(II) and coordinates via thione-S and thiazol-N.
Introduction
Important properties of thiourea to biological systems and some of their derivatives can regulate many pharmacological activities due to which they are important in medicinal chemistry. Thiourea and its derivatives are useful as antioxidants, fungicides, herbicides, antibacterial.
Thiazole is compound has a stable heterocyclic, ring at various positions led to synthesis of variety of novel compounds with wide spectrum of pharmacological activities such as antibacterial, antifungal. Anti-inflammatory, antiHIV, antitumor, anticonvulsant, …
Experimental
We prepared ligand by mixing 1:1molar ratio of 2-amino-4- methylthiazol (0.01mol) and phenyl isothiocyanate (0.01mol) ,complexes by mixing 1:1 and 1:2 molar ratio of metals to ligand respectively .
Infrared spectra
IR spectrum of the ligand displays two bands at 3340 cm-1 and 3165cm-1, attributable to υ(N1–H), υ(N2-H), respectively. The bands at 1195 and 650 cm-1 was displays which attributable to υ(C=S) and (S1=thiazole ring) and υ(CS1) +δ(N2-H), respectively
1H,13C NMR spectra
1H NMR all prepared compounds showed a N2H proton signal while the N1H proton disappears. This indicates that (HL) may be coordinated with metal ions by removing the N1H proton. The 13C NMR spectra was revealed that the signals of all carbon atoms of the compounds.
Electronic spectra and magnetic behavior
[NiL12] complex showed two bands at 16,000 and 21,000 which are characteristic for square-planar.
Pd(II) and Pt(II) complexes showed a broad absorption band at λmax = 330 nm and its end extends up to approximately 550 nm, obscuring the weak d-d transition. This is a predominant phenomenon in the square-planar Pd(II) and Pt(II) complexes containing sulfur as a donor atoms.
Conclusions
The results proved that ligang (PhMeTzTu) acts as bidentate coordinating of endocyclic-N and thiourea-S atoms to the metals. A square planar geometry in case of all complexes.