Resume

• 2016

  Nevakar Inc.

  Bridgewater

  NJ

  Director

  Assoc. Director

  Nevakar Inc.

• 2013

  Unilife Corporation

  Served as an analytical and pharmaceutical sciences expert

  supported development of injectable drug delivery systems by advancing analytical methodologies

  by implementing novel methods

  and by testing materials

  components

  and devices.\n\n• Designed and directed extractables and leachables studies for different product platforms; Introduced new analytical service providers and aggressively negotiated analytical services proposals; The improved supply-chain robustness and flexibility resulted in quicker execution and significant cost reductions.\n• Completed comprehensive heat-penetration studies coupled with endotoxin degradation analysis (kinetic chromogenic LAL assay); The results are critical for pre-fillable syringe material selection and depyrogenation process development.\n• Supported siliconization process development by evaluating the silicone distribution using spectral reflectance interferometry

  by developing and validating ICP-AES and FTIR methods to quantitate extractable silicone oil on drug delivery devices and components.\n• Designed

  directed

  and executed multiple gas permeation studies to determine Water Vapor Transmission Rate (WVTR) and Oxygen Transmission Rate (OTR) for pre-fillable syringes; The data are essential for material selection and product development.\n• Developed polymer-film gas sensors for modeling ethylene oxide sterilization of injectable drug delivery systems.

  Sr. Principal Scientist

  Greater Philadelphia Area

  Unilife Corporation

• 2011

  Johnson and Johnson

  Product and Process Scientific Solutions

  Spring House

  PA

  Provided Analytical Chemistry support for the complaint management and development of combination

  pharmaceutical

  and consumer products using state of the art chromatography

  spectroscopy

  and mass spectrometry instrumentation.\n\t \n• Implemented an efficient process for sample handling and testing in support of customer complaint investigations (OTC medications); comprehensive multi-technique analysis was completed and reported with a turnaround time less than 15 days

  on average 5 days per investigation – an important contribution to fulfilling company's obligation under the Consent Decree.\n• Led a 10+ member analytical team supporting complaint investigations; Responsible for data interpretation and report preparation

  maintenance of a project matrix; Applied statistical methodology to project metrics to reduce turnaround time.\n• Served as an analytical lead for a cross-functional team developing lubricious coating for a AAA stent graft system; directed analytical support (HPLC

  LC-MS

  FTIR) for polymeric subassemblies and washing process development; developed a residual solvent method (HS-GC) and completed testing for 5 developmental studies\n• Served as an analytical lead for a cross-company team engaged in development of an antibiotic and bioresorbable polymer-coated orthopedic implant); Achieved major milestones serving as the analytical lead: validation of 3 test methods (drug assay

  dissolution

  polymer amount and molecular weight)

  completion of a stability study.\n• Developed and utilized size-exclusion chromatography (SEC)

  FTIR micro-spectroscopy

  and light microscopy methods in support of manufacturing investigations and forensic assessment of suspected counterfeit products.

  Principal Scientist

  Johnson and Johnson

  Product and Process Scientific Solutions

• 2005

  Cordis

  a Johnson and Johnson company

  Spring House

  PA

  Responsible for understanding degradation kinetics and mechanisms for API and excipients on combination products (drug-eluting stents

  coated orthopedic implants); provided analytical support

  characterized raw materials.\n\n• Directed work of a team of 3-5 scientists conducting stability and forced degradation studies in support of CMC dossier preparation for Sirolimus-eluting stents.\n• Fully supported setup and qualification of two new GxP-compliant laboratories; evaluated and purchased laboratory equipment.\n• Discovered new degradation mechanisms for Sirolimus-eluting stents with a bioresorbable polymer. The results were essential for new product development.\n• Elucidated effects of E-beam sterilization on drug-eluting stents; by using LC-MS-MS determined sterilization-related degradation mechanisms that were essential for new product development.\n• Designed and developed a novel mixed-mode (SEC and adsorption) method for Sirolimus-eluting stents. This method for all-component quantitation and molecular weight analysis provides significant cost reductions.\n• Pioneered the use of the FTIR detection (solvent-free interface) for liquid chromatography to to support manufacturing investigations for medical devices and combination products.\n• Designed user requirements for qualification of computerized analytical instruments.

  Staff Scientist

  Principal Scientist

  Cordis

  a Johnson and Johnson company

• 2002

  Wichita State University

  • Developed novel fluorescent probes for non-orthodox protonable DNA structures that are central for understanding certain disease mechanisms.\n• Explored acid-base reactions of DNA oligomers and nucleotides with UV and IR spectroscopies combined with two-dimensional (2D) correlation analysis (homemade software). \n• Designed

  synthesized

  and characterized (NMR

  TLC

  GC-MS

  laser spectroscopy

  kinetics) novel caged compounds suitable for two-photon excitation to expand the range of their biological applications.\n• Achieved better understanding of polyelectrolyte/surfactant interactions in aqueous solutions by using FTIR and novel fluorescent probes undergoing excited-state proton transfer.\n• Awarded an ACS - Petroleum Research Fund grant; published 9 papers in peer-reviewed journals.\n• Modernized the Physical Chemistry curriculum and introduced new graduate courses. Supervised graduate students and postdoctoral research assistants.

  Wichita State University

• 1999

  Duke University

  ▪ Initiated and conducted studies of interactions of toxic fungal metabolites with proteins and DNA. Characterized toxin- and drug-protein complexes by using time-resolved fluorescence spectroscopy

  photochemistry

  native and SDS-PAGE

  protein digestion

  CD

  LC-MS and MALDI-TOF mass-spectrometry.\n▪ Developed methods to probe biological activity of toxic organic compounds by using their photochemistry. \n▪ Utilized GAUSSIAN molecular modeling and photophysical techniques in exploring structure and reactivity of melanin pigments and their building blocks. \n▪ Characterized human cryptochromes and their analogs using fluorescence spectroscopy.\n▪ Supported collaborative studies of structure-reactivity relationships for DNA-mediated electron transfer\n▪ Clarified mechanisms of photodecomposition of several antibacterial drugs. \n▪ Designed and constructed computerized time-correlated single-photon counting instruments.

  Duke University

  PDA

  Russian

  English

  German

  5.0 of 5.0

  Ph.D

  Chemical Kinetics and Catalysis

  Lomonosov Moscow State University (MSU)

  Bachelor of Science (BS)

  Chemistry

• OTA.pdf

  Toxic fungal metabolites

  their interactions with proteins and DNA

  photochemistry

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  Ochratoxins: Using Photoreactivity to Probe Toxicity Mechanisms

  Effects of E-BEAM Sterilization on Drug-Eluting Stents: Paclitaxel Degradation Elucidated by LC-MS-MS with Information-Dependent Acquisition

  Photochemistry: Theoretical Concepts and Reaction Mechanisms

  Yuri V. Il'ichev Cordis Corporation

  a Johnson and Johnson Company P.O. Box 776

  Welsh and McKean Roads

  Spring House

  PA 19477-0776 iilitche@its.jnj.com 1. Chemistry of Electronically Excited States Aren't you excited already? Not yet? Let us then adopt a step-by-step approach in order to introduce you to a fascinating world of excited-state reactions.

  Photochemistry: Theoretical Concepts and Reaction Mechanisms

  Department of Chemistry

  Moscow State University

  The Chemistry Department of Moscow State University is a world-known center for Chemistry education. Chemistry education at the University started from the year it was founded

  1755. The founder of Moscow University

  Michael Lomonosov

  was one of the best chemists in his time.

  Department of Chemistry

  Moscow State University

  Degradation of rapamycin and its ring-opened isomer: Role of base catalysis

  PC-Pacific05.pdf

  Probing protonable DNA structures with a fluorescent base analog

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  Abstract Proton-transfer reactions in aqueous solutions of poly(methacrylic acid) (PMA) were studied using a fluorescent probe and Fourier transform infrared (FTIR) spectroscopy. Protolytic photodissociation of 1-hydroxypyrene (HP) in water was found to be very slow. The PMA polyanion appeared to be very inefficient as a proton acceptor in the excited-state reaction with HP.

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  Excited-State Proton Transfer in Complexes of Poly(methacrylic acid) with Dodecyltrimethylammonium Chloride - Langmuir (ACS Publications)

  Drug Development

  Surfactants

  Fluorescence Spectroscopy

  Medical Devices

  Methods Development

  Biopolymers

  Kinetics

  Photochemistry

  Chromatography

  Polymer Characterization

  R&D

  Physical Chemistry

  Bioanalytical Chemistry

  IR spectroscopy

  LC-MS

  Validation

  Complaint Investigations

  Analytical Chemistry

  Light Scattering

  Supervisory Experience

  Excited-State Proton Transfer in Complexes of Poly(methacrylic acid) with Dodecyltrimethylammonium Chloride

  Svetlana V. Kombarova

  Proton-transfer reactions in aqueous solutions of poly(methacrylic acid) (PMA) were studied using a fluorescent probe and Fourier transform infrared (FTIR) spectroscopy. Protolytic photodissociation of 1-hydroxypyrene (HP) in water was found to be very slow. The PMA polyanion appeared to be very inefficient as a proton acceptor in the excited-state reaction with HP. However

  a drastic increase in the deprotonation efficiency was observed in PMA solutions with the same pH values close to neutral when dodecyltrimethylammonium chloride (DTAC) was added. The protonated form of HP

  as well as its anion

  was shown to be solubilized in polyion-covered micelles. Time-resolved fluorescence data suggested at least two localization sites with different reactivities toward PMA. FTIR spectroscopy was used to quantify the degree of ionization of PMA in PMA−DTAC mixtures. The IR data indicated that protolytic dissociation of PMA could be well described by the Henderson−Hasselbach equation with an apparent pK of 6.6. In contrast

  the fluorescent data revealed cooperative protonation of the PMA groups interacting with HP localized within surfactant assemblies. This selective protonation at a pH close to neutral may be associated with a conformational transition in the polymer−surfactant complex.

  Excited-State Proton Transfer in Complexes of Poly(methacrylic acid) with Dodecyltrimethylammonium Chloride

  Richard A. Manderville

  Annie Pfohl-Leszkowicz

  Virginie Faucet

  John B. Pritchard

  Daniel A. J. Bow

  Gyungse Park

  Jian Dai

  Ochratoxins are a class of naturally occurring compounds produced by several fungi. The most toxic is ochratoxin A (OTA)

  and occurrence of some human nephropathies and tumors correlate with enhanced OTA exposure. In this Account

  the following areas are examined:  molecular details of the binding of OTA to human ser-um albumin (HSA)

  the influences of binding to HSA on the trans-port of OTA across epithelial cell membranes by organic anion transport proteins

  the oxidative activation of OTA

  and the for-mation of OTA adducts with biological molecules. These studies are beginning to provide a detailed chemical model for the trans-port

  accumulation

  and genotoxic and carcinogenic effects of OTA.

  Molecular Aspects of the Transport and Toxicity of Ochratoxin A

  Cynthia A. Maryanoff

  Rapamycin is a natural macrolide immunosuppressant with a distinct mechanism of action. Quantitative analysis of rapamycin poses many challenges associated with facile degradation and the multitude of isomeric forms. The primary goal of this study was to compare degradation of rapamycin and its ring-opened isomer

  secorapamycin

  in aqueous solution under identical conditions. Reaction kinetics and mechanisms were studied in 30/70 vol/vol acetonitrile-water mixtures containing either MeCOONH4 (apparent pH 7.3) or NaOH (apparent pH 12.2). Degradation kinetics was well described by the first-order rate law. For rapamycin in 237 and 23.7 mM solutions of MeCOONH4

  apparent half-lives of 200 h and 890 h were obtained. When compared to the latter value

  the rapamycin half-life was reduced by 3 orders of magnitude in the pH 12.2 solution. Under all conditions studied

  secorapamycin degradation was significantly slower than that of the parent compound. Both specific and general base catalysis was observed for reactions of rapamycin and secorapamycin. Two primary products of rapamycin degradation were identified as individual isomers of secorapamycin and a hydroxy acid formed via lactone hydrolysis. No evidence for the interconversion between the products was obtained. In highly basic solutions

  both products undergo fragmentation and water addition reactions.

  Degradation of rapamycin and its ring-opened isomer: Role of base catalysis

  Effects of sterilization by electron beam (E-BEAM) on paclitaxel (1) mixed with poly(DL-lactide-co-glycolide) (PLG) in reservoirs of COSTAR Stents are examined by using liquid chromatography-mass spectrometry (LC-MS-MS) techniques with information-dependent acquisition (IDA). Numerous degradation products of 1 are formed in a β-radiation dose-dependent manner to give plethora of low-level degradants. This behavior

  together with multiple interferences from PLG-related compounds

  creates considerable challenges for analysis of the drug/PLG mixtures. IDA methods with different survey scans are proven to be very efficient in elucidating degradation pathways and in identifying numerous products. Combined LC-MS-MS results from analysis of sterilized drug substance and stents indicate that water addition and oxidative processes together with the isomerization are largely responsible for degradation of 1 under E-BEAM sterilization conditions used.

  Effects of E-BEAM Sterilization on Drug-Eluting Stents: Paclitaxel Degradation Elucidated by LC-MS-MS with Information-Dependent Acquisition

  Optical spectroscopy was used to examine the binding of ochratoxin A (OTA) and warfarin (WAR) to human serum albumin (HSA). Both molecules in the deprotonated form showed high affinity binding to HSA. The close proximity of the highest affinity binding site of the OTA dianion to that of the WAR monoanion was suggested by depolarization of WAR emission in ternary mixtures with [OTA]/[WAR] ≥ 3. Fluorescence polarization data also showed that both OTA and WAR simultaneously bind to HSA for 0.1 ≤ [OTA]/[WAR] ≤ 1. The failure of WAR to displace OTA under these conditions is in accord with the much smaller binding constant for WAR. In all displacement experiments either the HSA-to-WAR or HSA-to-OTA concentration ratio was kept constant and close to unity. Evidence of energy transfer from electronically excited WAR to OTA when both species are bound to HSA was obtained from fluorescence emission data. The efficiency of this energy transfer provided an estimate of 27 Å as the upper limit of the distance between WAR and OTA. WAR bound to HSA strongly quenched the fluorescence of the single tryptophan residue

  Trp214. However

  the quenching mechanism was different from the energy transfer mechanism observed for quenching of WAR by OTA. The results show that OTA and WAR share a common binding site in subdomain IIA

  with OTA having a higher binding affinity. In addition

  WAR can occupy another binding site on HSA when OTA is bound. The data suggest that a secondary binding site of OTA is located in domain III

  while that of WAR is in domain I.

  Interaction of Ochratoxin A with Human Serum Albumin. A Common Binding Site of Ochratoxin A and Warfarin in Subdomain IIA

  Ochratoxin A (OTA)

  a fungal metabolite produced by several strains of Aspergillus and Penicillium

  binds to serum albumin with high affinity only in the completely deprotonated form (dianion). The pKa of the phenolic group of OTA decreased by more than three units when it was bound to human serum albumin (HSA). Optical spectroscopy provided evidence that HSA has at least two binding sites for OTA

  each being able to accommodate one dianion. These two sites were characterized by the binding constants of 5.2 × 106 and 1.0 × 105 M-1. The binding constant for the monoanion of OTA was estimated to be 103 M-1. Fluorescence polarization spectroscopy confirmed weak interaction of the monoanion with the protein in the F and E forms (pH < 4) and showed lower affinity of the dianion to the B form of HSA (pH > 8) compared to the N form (pH 7). Fluorescence anisotropy decay of the dianion of OTA bound to HSA (36.6 ns) was much longer than its emission lifetime (5.2 ns) and was close to reported values for the rotational tumbling time of the HSA molecule. Results of chemical denaturation with 9 M urea or 5 M guanidine hydrochloride established that high-affinity binding of OTA only occurred to the native protein. Efficient energy transfer from the single tryptophan residue of HSA (Trp214) to bound OTA was observed. Analysis of fluorescence data provided an estimate of the distance between the dianion of OTA in its highest-affinity site and the Trp214 residue

  which was on the order of 16 Å. The results are discussed with respect to recent crystallographic data for HSA−ligand complexes and pH-dependent conformation of HSA.

  Interaction of Ochratoxin A with Human Serum Albumin. Preferential Binding of the Dianion and pH Effects

  Cynthia A. Maryanoff

  Patrick Achord

  Richard Dunphy

  Ann Polshyna

  Yanqiu Sun

  The immunosuppressant drug rapamycin

  also known as Sirolimus

  underwent autoxidation under mild conditions to give numerous monomeric and oligomeric compounds

  which were generally characterized by size-exclusion chromatography and NP-HPLC with UV and MS detection. Some of the more predominant products

  epoxides and ketones

  were isolated and identified. Two epoxides and 10S-epimer of rapamycin were described for the first time. Observed rapamycin isomers were also addressed. Computational chemistry was used to provide mechanistic insights. Formation of the majority of the rapamycin products could be rationalized with free radical-mediated autoxidation reactions involving alkene and alcohol sites. Methodological aspects of oxidative stress testing are discussed.

  Forced degradation studies of rapamycin: Identification of autoxidation products

  Yuri V.

  Ilitchev