Project Summary/Abstract The Institute for Innovation in Imaging (i3) at the Massachusetts General Hospital (MGH) seeks funds to purchase an LC-MS system with UPLC capability to replace and upgrade a heavily used, aging single quadrupole electrospray LC-MS system. The current single quadrupole LC-MS has served as a robust instrument for monitoring chemical reactions, confirming purity and identity of pharmaceutical products and synthetic intermediates, and detecting stability of target compounds for investigational new drug (IND) applications. The current single quadrupole LC-MS has been vital to the NIH-funded projects associated with this proposal. LC-MS is critical to any pharmaceutical or medicinal chemistry research. LC-MS is routinely used to monitor chemical reactions and to confirm purity and identity of small molecular pharmaceutical products. Our robust single quadrupole system has supported the chemical synthesis of countless experimental molecular imaging probes. Among the PIs associated with this proposal, data collected on that LC-MS system has been included in >100 scientific papers. No credible scientific journal will accept reports of new small molecule and peptide-based pharmaceutical entities without sufficient characterization of purity and identity, which are most commonly quantified using LC and MS, respectively. Data collected on the LC-MS system has been key to the majority of the i3-enabled patent applications and investigational new drug application filings. The LC-MS also has been used to directly support clinical trials performed at MGH. There is a need to replace the i3 LC-MS. The current single quadrupole LC-MS is a workhorse instrument for chemists working at the MGH Charlestown campus. It was purchased in 2013 and is now more than 10 years old. Component failures are expected with well-used equipment but have become increasingly frequent and costly over the last four years. In the past four years, the LC-MS had to be shut down multiple times to replace the computer mainboard, repair leaks in loop injector, repair leaks in the pump valves, repair the multisampler needle seat, repair the pump motor, repair the electron multiplier on the MS. As of today, the pressure of the HPLC is unstable when using solvent lines C and D resulting in poor chromatographic separation. As such, users are reduced to using a single chromatographic condition (lines A and B). Despite having a service contract and performing daily maintenance, the availability of our LC-MS decreased significantly since 2022, and more downtime is expected in the coming months as the instrument is approaching the end of its life. The single quadrupole LC-MS remains a mainstay for chemistry research, but we expect instrument downtime and maintenance costs to increase dramatically as the instrument continues to age, necessitating the proposed replacement. The proposed instrumentation will allow us to continue offering the analytical and bioanalytical chemistry capabilities to NIH-supported scientists and enable or accelerate research activities of 20 projects currently funded by 6 NIH institutes, as well as emergent projects that have not yet received federal funding.

The i3 seeks to replace a heavily used aging single quadrupole electrospray LC-MS system with a tandem ultrahigh pressure liquid chromatography and mass spectrometer (LC-MS) system that offers substantial advantages over our current experimental configurations.