Principal Scientist - Biotransformation

Inotiv • St. Louis, MO

4d

About The Position

The Principal Scientist of Biotransformation will assist with the identification of enzymatic pathways that metabolize drug candidates in preclinical in vitro and in vivo models, including human tissue and cellular models (e.g., P450, non P450/AO/FMO, conjugative/UGT). Working primarily with preclinical species and human tissues/organ subcellular fractions, the individual will utilize contemporary mass spectrometry techniques (LC-MS/MS) to identify and elucidate the structures of drug metabolites (small molecules, peptides, oligonucleotides). The individual will contribute to the development of in vitro-to-in vivo relationships related to drug clearance & half-life predictions. The individual will collaborate with Pharmacology and Toxicology laboratory leadership to establish Novel Approach Methodologies (NAMs) to address mechanistic inquiries and/or platform screening processes for same. Join us in embracing research and science to impact the health and well-being of people all over the world. Essential Duties and Responsibilities Design and execute laboratory studies aimed at identifying the enzymatic pathways that metabolize small molecule, peptide, and oligonucleotide therapeutics employing a contemporary approach methodology to establish the primary enzyme(s) contributing to the in vitro metabolism of a drug candidate(s). Design and execute laboratory studies to elucidate primary drug clearance mechanisms in vitro, employing contemporary approach methodology to establish in vitro to in vivo correlations for anticipated drug clearance towards the prediction of human half life. Design and collaborate with in vivo pharmacology & toxicology team members to execute ADME studies (non radiolabeled); elucidating the disposition of drug candidate molecules as it pertains to absorption, distribution, metabolism, and excretion; supplementing with in vitro protein binding, and blood distribution For oligonucleotide and peptide molecules, design and execute in vitro studies aimed at elucidating the exonuclease/endonuclease and peptidase(s) metabolism of drug candidates, respectively. Collaborate with the Toxicology Department to establish cellular models of drug metabolism, induction, and predictive toxicologic mechanisms.

Requirements

• Experience conducting in vitro and ex vivo biotransformation assays utilizing LC–MS/MS techniques for quantitation and structure elucidation.
• Experience, skills, and abilities must include knowledge of contemporary bioanalytical techniques, including wet chemistry separations, liquid chromatography, and mass spectrometric analysis, instrument operation, and data processing.
• Knowledge of enzyme kinetics desirable.
• Ability to incorporate software in the maintenance of databases to collate and catalog records and inventory.
• Independence in the laboratory and data work-up phases of research.
• A working knowledge and awareness of general laboratory procedures.
• Good written and oral communication skills.
• Ability to adhere to all safety regulations and procedures.
• PhD in Organic Chemistry, Biochemistry, Analytical Chemistry or related discipline with 2-5 years direct industrial biotransformation experience following Post Doctoral training
• M.Sc. in a discipline previously described with 5-7 years direct industrial biotransformation experience
• Working command of in vitro kinetic analysis and utilization of contemporary mathematical models to effectively analyze, interpret and/or model drug clearance, predicted half life, and drug-drug interactions
• Ability to perform mass spectrometry data collection, analysis and interpretation experience via LC-MS/MS

Nice To Haves

• Candidates possessing a command of Pharmacokinetic modeling, analysis, interpretation and simulation desirable

Responsibilities

• Design and execute laboratory studies aimed at identifying the enzymatic pathways that metabolize small molecule, peptide, and oligonucleotide therapeutics employing a contemporary approach methodology to establish the primary enzyme(s) contributing to the in vitro metabolism of a drug candidate(s).
• Design and execute laboratory studies to elucidate primary drug clearance mechanisms in vitro, employing contemporary approach methodology to establish in vitro to in vivo correlations for anticipated drug clearance towards the prediction of human half life.
• Design and collaborate with in vivo pharmacology & toxicology team members to execute ADME studies (non radiolabeled); elucidating the disposition of drug candidate molecules as it pertains to absorption, distribution, metabolism, and excretion; supplementing with in vitro protein binding, and blood distribution
• For oligonucleotide and peptide molecules, design and execute in vitro studies aimed at elucidating the exonuclease/endonuclease and peptidase(s) metabolism of drug candidates, respectively.
• Collaborate with the Toxicology Department to establish cellular models of drug metabolism, induction, and predictive toxicologic mechanisms.

Benefits

• Benefits include health and dental coverage, short- and long-term disability, paid time off, paid parental leave, 401K participation with company match, and more!
• Salary will be commensurate with experience and responsibilities.

What This Job Offers

• Job Type: Full-time
• Career Level: Principal
• Education Level: Ph.D. or professional degree
• Number of Employees: 1,001-5,000 employees