Kenneth L. Morand

The Effect of Freeze/Thaw Cycles on the Stability of Compounds in DMSO

A diverse set of 320 compounds from the Procter & Gamble Pharmaceuticals organic compound repository was prepared as 20-mM DMSO solutions and stored at 4°C under argon in pressurized canisters to simulate a low-humidity environment. The plates were subjected to 25 freeze/thaw cycles while being exposed to ambient atmospheric conditions after each thaw to simulate the time and manner by which compound plates are exposed to the atmosphere during typical liquid-handling and high-throughput screening processes. High-performance liquid chromatography–mass spectrometry with evaporative light-scattering detection was used to quantitate the amount of compound remaining after every 5th freeze/thaw cycle. Control plates were stored either at room temperature under argon or at 4°C under argon without freeze/thaw cycling and were evaluated at the midpoint and the endpoint of the study. The study was conducted over a short time period (i.e., 7 weeks) to minimize the effect of compound degradation over time due to the exposure of the compounds to DMSO.The results from this study will be used to determine the maximum number of freeze/thaw cycles that can be achieved while maintaining acceptable compound integrity.(Journal of Biomolecular Screening 2003:210-215)

The Effect of Room-Temperature Storage on the Stability of Compounds in DMSO

The stability of approximately 7200 compounds stored as 20-mM DMSO solutions under ambient conditions was monitored for 1 year. Compound integrity was measured by flow injection analysis using positive and negative electrospray ionization mass spectrometry. Each sample was assessed at the beginning of the study, after 12 months of storage, and at a randomized time point between the initial and final time points of the study. The relationship between length of storage and the probability of observing the compound was described by a repeated-measures logistic regression model. The probability of observing the compound was 92% after 3 months of storage at room temperature, 83% after 6 months, and 52% after 1 year in DMSO. An acceptable limit for compound loss and corresponding maximum storage time for samples in DMSO can be determined based on these results.(Journal of Biomolecular Screening 2003:205-209)

A tandem quadrupole-ion trap mass spectrometer

Abstract A new tandem mass spectrometer has been constructed by interfacing a Paul ion trap mass spectrometer to a quadrupole mass filter. Ions generated in an EI—CI source are mass-selected using the quadrupole and injected in 50–100 ms pulses into the ion trap at injection energies which range from nominally zero to 150 eV. Helium gas at a pressure of 1 mTorr is used to dampen the ion motion and thus trap the injected ions. Stored ions, as well as their dissociation and ion/molecule reaction products, are detected using the mass-selective instability scan mode of the ion trap. Ions generated from perfluorotributylamine, polycyclic aromatic hydrocarbons, xenon and tungsten hexacarbonyl all show efficient trapping at injection energies ranging from 10 to 110 eV. As the injection energy is raised, the internal energy deposited in the projectile increases, as demonstrated by displaying fragment ion abundances versus injection energy in the form of breakdown curves. Pyrene and other PAH ions undergo extensive fragmentation at injection energies ⩾ 100 eV to give spectra which resemble those recorded using surface-induced dissociation (SID). These and other data suggest that ions injected with sufficient kinetic energies collide with the trap surface during injection. Gas phase ion/molecule reactions also occur and lead to formation of [M + 17]+ from PAH molecular ions and abundant dinuclear ions from tungsten hexacarbonyl. The new instrument is evaluated and compared with other tandem mass spectrometers.

Mass spectrometers: instrumentation

Abstract Developments in mass spectrometry instrumentation over the past three years are reviewed. The subject is characterized by an enormous diversity of designs, a high degree of competition between different laboratories working with either different or similar techniques and by extremely rapid progress in improving analytical performance. Instruments can be grouped into genealogical charts based on their physical and conceptual interrelationships. This is illustrated using mass analyzers of different types. The time course of development of particular instrumental concepts is illustrated in terms of the s-curves typical of cell growth. Examples are given of instruments which are at the exponential, linear and mature growth stages. The prime examples used are respectively: (i) hybrid instruments designed to study reactive collisions of ions with surfaces: (ii) the Paul ion trap; and (iii) the triple quadrupole mass spectrometer. In the area of ion/surface collisions, reactive collisions such as hydrogen radical abstraction from the surface by the impinging ion are studied. They are shown to depend upon the chemical nature of the surface through the use of experiments which utilize self-assembled monolayers as surfaces. The internal energy deposited during surface-induced dissociation upon collision with different surfaces in a BEEQ instrument is also discussed. Attention is also given to a second area of emerging instrumentation, namely technology which allows mass spectrometers to be used for on-line monitoring of fluid streams. A summary of recent improvements in the performance of the rapidly developing quadrupole ion trap instrument illustrates this stage of instrument development. Improvements in resolution and mass range and their application to the characterization of biomolecules are described. The interaction of theory with experiment is illustrated through the role of simulations of ion motion in the ion trap. It is emphasized that mature instruments play a dominant role in most work using mass spectrometers. This is illustrated with recent results on the chemistry of C+.60 including the formation of covalent adducts with aromatic compounds. Quantitative analysis of methylated nucleosides and structural studies of the anti-cancer drug taxol are also discussed. A compendium of mass spectrometers constructed over the past three years is provided. This includes a variety of hybrid instruments, combinations of sector mass spectrometers with traps, instruments designed to study collision dynamics, and many more.