Aaron L. Smith, Hasse Walum, Fawn Connor-Stroud, Sara M. Freeman, Kiyoshi Inoue, Lisa A. Parr, Mark M. Goodman, Larry J. Young
The physiology of the oxytocin receptor has increasingly become a focus of scientific investigation due to its connection with social behavior and psychiatric disorders with impairments in social funciton. Experimental utilization of small molecule and peptide antagonists for the oxytocin receptor has played a role in deciphering these biological and social behavior connections in rodents. Described herein is the evaluation of a potent and selective oxytocin receptor antagonist, ALS-I-41, and details to consider for its use in nonhuman primate behavioral pharmacology experiments utilizing intranasal or intramuscular administration. The central nervous system penetration and rate of metabolism of ALS-I-41 was investigated via mass spectroscopy analysis of cerebrospinal fluid and plasma in the rhesus macaque after intranasal and intramuscular administration. Positron emission tomography was also utilized with [18F] ALS-I-41 in a macaque to verify observed central nervous system (CNS) penetration and to further evaluate the effects of administration rate on CNS penetration of Sprague-Dawley rats in comparison to previous studies.
The LC/MS analysis was carried out using Advion Expression® CMS.
Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH? A: Our work is focused on the development and implementation of chromatographic purification processes, ranging from mg to 100 kg scale. Many compounds of interest lack chromophores and cannot be detected by classical UV detection.
Q: WHAT WAS YOUR PREVIOUS WORKFLOW AND EXPERIENCED CHALLENGES?
A: In the past, the fraction collection during preparative HPLC was very time consuming as we had no indicator when the compound of interest was eluting in the chromatographic process in case it was not UV-active. All fractions had to be analyzed by TLC and in many cases additionally with HPLC and Corona detection before we could identify the fractions of interest.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: We use the Advion Interchim Scientific expression® CMS as a robust and versatile detector in our chromatographic processes, both MPLC and HPLC. The data transfer into the control software of our prep HPLC systems was straightforward. The Advion MS is shared with our R&D department for more conventional applications and gave both departments very quick access to MS data. Both departments appreciated the quick set-up, the user-training, and the reliable after sales service whenever a question pops up.
Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION® CMS?
A: The Advion MS is a robust instrument that can be used in different environments. It does not require a lot of training and is easy to understand. Whenever you have a need for MS data, be it online or offline, Advion MS might give you very easy access to the data you need.
Shared live at the 254th ACS National Meeting in Washington, D.C. –
John Matson, Ph. D., Matson Research Group on Macromolecular and Supramolecular Chemistry, Assistant Professor, Virginia Tech.
Listen to the recorded workshop session highlighting the role of H2S in the human body and how compact mass spectrometry is used to assay peptides via direct injection for reaction monitoring, and coupled with HPLC for purification.
Introducing a new type of mass spectrum, available exclusively in the Advion Peak Express™ software suite: the Delta Spectrum (ΔS). The ΔS is available with the expression® compact mass spectrometer (CMS) to look beyond chemical noise and automatically detect even the smallest peaks without knowing the m/z in advance.
With the Peak Express™ software featuring ΔS, you can:
Obtain clear detection of peaks without knowing their mass
Find adducts, dimers, fragments, side-reactions and other unexpected compounds at the click of a button, in real-time or with post-processing
Highlight minor components in complex mixtures and dirty matrices
Control mass-directed purification without providing the compound mass
Acquire XIC-quality data while scanning the entire mass range, allowing Peak Express™ to tell you the m/z
Advion Interchim Scientific’s range of AVANT®, high performance, liquid chromatography systems can be used standalone with UV and UV/Vis detector options, or with the expression® compact mass spectrometer to provide seamlessly integrated LC/CMS under the full control of Advion Interchim Scientific’s simple, intuitive Mass Express software suite.
Modular, stackable design, with many options, provides custom solutions for both HPLC and UHPLC needs. From the simplest manual injection HPLC to a fully automated, streamlined UHPLC system and everything in-between, the AVANT® series can be configured to fit your analytical requirements and your budget.
The novel Peak Express™ technology was evaluated and applied to natural product extracts.
Peak Express™ utilizes delta ion currents, a differential ion current with significantly improved signal-to-noise as well as enhanced detection ability for low abundance compounds.
Cost effective, multidimensional GRAS (generally recognized as safe) counterfeit protection of drugs based on uniformly 13C labeled amino acids with compact mass spectrometry detection.
Quant Express, an addition to Advion’s user-friendly Mass Express 4.0 software suite, features quantitation to create a fully integrated software system for expression CMS users.
Introducing a new type of mass spectrum, available exclusively in the Advion Peak Express™ software suite: the Delta Spectrum (ΔS). The ΔS is available with the expression compact mass spectrometer (CMS) to look beyond chemical noise and automatically detect even the smallest peaks without knowing the m/z in advance.
With the Peak Express™ software, you can:
Find minor components and impurities you would otherwise miss
Find unknowns in complex samples like natural products
Acquire XIC-quality data while scanning the entire mass range, allowing Peak Express™ to tell you the m/z
Perform real-time, mass-directed purification without knowing the mass Realize automatic ‘expert’ data processing
The Drug Discovery Unit at the University of Dundee is met daily with a global task: address unmet medical needs and diseases in the developing world, and continuously build their innovative targets portfolio.
Learn from Susan Davis, a Medicinal Chemist with the unit, how she has processed 22,639 sample injections via the Advion compact mass spectrometer, and how it has assisted her research daily.
Also hear from Dr. Jack Henion, Advion’s Scientific Founder, as he joins for a Q&A session about mass spec and it’s role in drug discovery and disease prevention.
This webinar examines the workflow of a medicinal chemist as they utilize compact mass spectrometry techniques for drug discovery and disease prevention.
