Mass Spectroscopy Unit of the Institute for Drug Research Instrumentation The Mass Spec Unit of the Institute for Drug Research is offering services on three modern Mass Spectrometers with utmost professionalism: GC-MS/MS High Resolution and Accurate Mass GCxGC-MS/MS (Agilent 7200 GC/Q-TOF) combines high selectivity with the added value of accurate mass (<5ppm), high resolution, Electron (EI) and Chemical Ionization (CI), making it the ultimate choice for targeted and nontargeted screening as well as for quantitation analysis. Structural elucidation of unknown compounds may be achieved by accurate mass measurements, elemental composition calculations, isotopic patterns, database searching and fragmentation interpretation. Its expanded sampling range (a liquid, headspace and SPME injection system) makes it a powerful candidate for metabolomics, volatile compounds (VOC) and semivolatile compounds (SVOC) analysis. LC-MS/MS Two Triple Quadrupole Mass Spectrometers: Sciex Triple Quad TM 5500 Thermo TSQ Quantum Access Max Framingham, MA, USA San Jose, CA, USA The major application of these Triple Quadrupole Mass Spectrometers is the quantitation of small molecules (pharmaceuticals, natural products, small peptides, fatty acids, steroids, metabolites and contaminants among them) in diverse biological and complex matrices. These instruments are ideal for pharmacokinetic studies and quantitation of small amounts of the molecules in complex biological samples. Our Specialization The Mass Spec Unit specializes in a broad range of services for drug development research -clinical and preclinical studies- and the services are compatible with almost any small molecule (pesticides, environment contaminants, etc.) Identification of unknown compounds in complex mixtures especially volatile (VOC) and semivolatile (SVOC) compounds GC-MS/MS targeted and untargeted quantitative analysis of biological samples LC-MS/MS quantitative bioanalysis of pharmaceuticals, natural compounds and metabolites in biological matrices such as plasma, serum, tissues and urine. Kinetic studies of reaction mixtures Rapid structure confirmation for a wide range of small organic compounds and small peptides Mass Spec services are available to all users, both academic and industrial and include specialist support such as: Guidance in the choice of method for sample preparation Method development and validation Data analysis Consulting and advice in Mass Spec data interpretation The Mass Spec Unit is located at the School of Pharmacy building, floor -1, room No. 25, Ein Kerem Campus, The Hebrew University of Jerusalem, Jerusalem. For more information please contact: Dinorah Barasch, PhD Alina Nemirovski, PhD Tel: +972-2-6757394, Fax: +972-2-6757076, E-mail: [email protected] Successful projects accomplished Pharmacokinetics (PK) and organ distribution of small peptides, drugs (bupivacaine, methylprednisolone, rimonabant, streptozotocin, retinoids, docetaxel, paclitaxel, mitomycin C, lopinavir, sirolimus, florfenicol, ouabain, digoxin, ibuprofen, huperzine A, amoxicilline, ladostigil) and proprietary prodrugs after administration to mice, rats, pigs and sheep in diverse formulations, including liposomes, nanoparticles and nanocapsules Quantitative analysis of cannabinoids (THC, CBD & CBG), endocannabinoids fatty acids, and other endogenous compounds in plasma and different tissues Pharmacokinetics and metabolites quantification in human body fluids (plasma, saliva and urine) during clinical trials Quantitative analysis of amino acids in medium and determination of the uptake/release by cells Quantification of 13C-labeled Acetyl CoA in Embryonic Stem Cells Quantitative analysis of trace contaminants (DNT and TNT) in soil samples Structure confirmation of diverse labile metal complexes Identification of low concentrations of suspected illicit drugs and poisons in mixtures Quantitative analysis of diverse vitamins and hormones in complex mixtures Analysis of natural compounds, antioxidants and flavonoids in plant extracts Drug release profiling and stability studies of diverse drug formulations Selected publications 1. Zelber-Sagi, S.; Azar, S.; Nemirovski, A.; Webb, M.; Halpern, Z.; Shibolet, O.; Tam, J., Serum Levels of Endocannabinoids are Independently Associated with Nonalcoholic Fatty Liver Disease. Obesity 2017, 25 (1), 94-101. 2. Boo, H.-O.; Kim, H.-H.; Barasch, D.; Nemirovski, A.; Lee, M.-S.; Gorinstein, S.; Ku, Y.-G., Codonopsis lanceolata and Nelumbo nucifera Gaertn. root extracts for functional food: metabolic profiling by MS, FTIR and fluorescence and evaluation of cytotoxicity and anti-obesity properties on 3T3-L1 cell line. European Food Research and Technology 2017, 243 (4), 689-700. 3. Knani, I.; Earley, B. J.; Udi, S.; Nemirovski, A.; Hadar, R.; Gammal, A.; Cinar, R.; Hirsch, H. J.; Pollak, Y.; Gross, I.; Eldar-Geva, T.; Reyes-Capo, D. P.; Han, J. C.; Haqq, A. M.; Gross-Tsur, V.; Wevrick, R.; Tam, J., Targeting the endocannabinoid/CB1 receptor system for treating obesity in Pradere-Willi syndrome. Molecular Metabolism 2016, 5 (12), 1187-1199. 4. Leontowicz, H.; Leontowicz, M.; Latocha, P.; Jesion, I.; Park, Y. S.; Katrich, E.; Barasch, D.; Nemirovski, A.; Gorinstein, S., Bioactivity and nutritional properties of hardy kiwi fruit Actinidia arguta in comparison with Actinidia deliciosa 'Hayward' and Actinidia eriantha 'Bidan'. Food Chemistry 2016, 196, 281-291. 5. Leontowicz, M.; Leontowicz, H.; Namiesnik, J.; Apak, R.; Barasch, D.; Nemirovski, A.; Moncheva, S.; Goshev, I.; Trakhtenberg, S.; Gorinstein, S., Rapana venosa consumption improves the lipid profiles and antioxidant capacities in serum of rats fed an atherogenic diet. Nutrition Research 2015, 35 (7), 592-602. 6. Moussaieff, A.; Rouleau, M.; Kitsberg, D.; Cohen, M.; Levy, G.; Barasch, D.; Nemirovski, A.; Shen-Orr, S.; Laevsky, I.; Amit, M.; Bomze, D.; Elena-Herrmann, B.; Scherf, T.; Nissim-Rafinia, M.; Kempa, S.; Itskovitz-Eldor, J.; Meshorer, E.; Aberdam, D.; Nahmias, Y., Glycolysis-Mediated Changes in Acetyl-CoA and Histone Acetylation Control the Early Differentiation of Embryonic Stem Cells. Cell Metabolism 2015, 21 (3), 392-402. 7. Momic, T.; Katzhendler, J.; Shai, E.; Noy, E.; Senderowitz, H.; Eble, J. A.; Marcinkiewicz, C.; Varon, D.; Lazarovici, P., Vipegitide: a folded peptidomimetic partial antagonist of alpha 2 beta 1 integrin with antiplatelet aggregation activity. Drug Design Development and Therapy 2015, 9, 291-304. 8. Moradov, D.; Finkin-Groner, E.; Bejar, C.; Sunita, P.; Schorer-Apelbaum, D.; Barasch, D.; Nemirovski, A.; Cohen, M.; Weinstock, M., Dose-limiting inhibition of acetylcholinesterase by ladostigil results from the rapid formation and fast hydrolysis of the drug-enzyme complex formed by its major metabolite, R-MCPAI. Biochemical Pharmacology 2015, 94 (2), 164-172. 9. Nudelman, Z.; Findler, M.; Barasch, D.; Nemirovski, A.; Pikovsky, A.; Kirmayer, D.; Basheer, M.; Gutkind, J. S.; Friedman, M.; Czerninski, R., Levels of sirolimus in saliva and blood following oral topical sustained-release varnish delivery system application. Cancer Chemotherapy and Pharmacology 2015, 75 (5), 969974 10. Barasch, D.; Nemirovski, A.; Nassar, T., Non-conventional approach to quantitative analysis by LCMS/MS. Oral presentation at ISRANALYTICA 2015, The 18th Annual Meeting of the Israel Analytical Chemistry Society, Tel-Aviv, Israel. 11. Nudelman, Z.; Friedman, M.; Barasch, D.; Nemirovski, A.; Findler, M.; Pikovsky, 12. 13. 14. 15. 16. 17. A.; Gutkind, J. S.; Czerninski, R., Levels of sirolimus in saliva and blood following mouthwash application. Oral Diseases 2014, 20 (8), 768-772. Zivi, E.; Barash, D.; Aizenman, E.; Gibson, D.; Shufaro, Y., Zygote serine decreased uptake from the fertilization medium is associated with implantation and pregnancy. Journal of Assisted Reproduction and Genetics 2014, 31 (7), 889-897. Zivi, E.; Aizenman, E.; Barash, D.; Gibson, D.; Shufaro, Y., Use of culture media amino acid mass spectrometry/liquid chromotography (LCMS) measurments in identifing the embryo with the best implantation potential. Human Reproduction 2013, 28, 189-189. Karra, N.; Nassar, T.; Ripin, A. N.; Schwob, O.; Borlak, J.; Benita, S., Antibody Conjugated PLGA Nanoparticles for Targeted Delivery of Paclitaxel Palmitate: Efficacy and Biofate in a Lung Cancer Mouse Model. Small 2013, 9 (24), 42214236. Attili-Qadri, S.; Karra, N.; Nemirovski, A.; Schwob, O.; Talmon, Y.; Nassar, T.; Benita, S., Oral delivery system prolongs blood circulation of docetaxel nanocapsules via lymphatic absorption. Proceedings of the National Academy of Sciences of the United States of America 2013, 110 (43), 17498-17503. Burshtein, G.; Friedman, M.; Greenberg, S.; Hoffman, A., Transepithelial Transport of a Natural Cholinesterase Inhibitor, Huperzine A, along the Gastrointestinal Tract: the Role of Ionization on Absorption Mechanism. Planta Medica 2013, 79 (3-4), 259-265. Nudelman, Z.; Keshet, N.; Elhalal, M. D.; Friedman, M.; Czerninski, R., Levels of Sirolimns in Saliva vs. Blood - the Rationale of Topical Oral Use for Oral Malignancy. Anticancer Research 2013, 33 (2), 661-663.
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