Thursday, November 21, 2024
11/21/2024
Project Summary/Abstract This proposal seeks funds to purchase a Sciex 6500+ Qtrap mass spectrometer with integrated Sciex M5 microflow UHPLC to become part of the drug metabolism and pharmacokinetic (DMPK) core. This system will be used to quantitate the concentration of small molecules in plasma and tissue samples from mouse pharmacokinetic studies. The Sciex 6500 Qtrap is ideally suited to this function and is the workhorse instrument for the analysis of PK samples in pre-clinical laboratories in the pharmaceutical industry. The Scripps DMPK core runs over 200 mouse PK studies per year and, when possible, utilizes microsampling techniques. Microsampling requires superior analytical sensitivity because the technique collects a limited sample, 5-10 µl plasma. The advantage of microsampling is that it allows triplicate PK data to be generated from three mice, instead of using twelve or twenty-four mice as have traditionally been required. Analysis of mouse pharmacokinetic samples in the Scripps DMPK core is currently done on a Sciex 5500 mass spectrometer. Microsampling techniques are currently utilized for approximately 80% of the compounds tested at the Scripps DMPK core. The decision to use microsampling or revert to a traditional large sample collection design using higher numbers of mice is based on the planned dose and an evaluation of the analytical limit of quantitation, which is determined prior to conduct of the in-life portion of the PK study. This shared instruments currently supports a range of research projects originating from multiple NIH funded projects associated with seven institutions. The level of engagement for each of these projects with the DMPK core is high, and the core is written into multiple HIN funded grants. To maximize the impact of NIHs investment and assure the instrument remains productive for a period of at least five years, Scripps guarantees maintenance and operational costs, including staff to oversee the instrument, and will purchase a service contract with the instrument manufacturer that will cover all repairs and yearly preventative maintenance for five years. This shared instrument will be installed in the Scripps Florida DMPK core and will be operated by a group of experienced mass spectroscopists within the DMPK core.
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