Richard H. Perry

Orbitrap mass spectrometry: instrumentation, ion motion and applications.

Since its introduction, the orbitrap has proven to be a robust mass analyzer that can routinely deliver high resolving power and mass accuracy. Unlike conventional ion traps such as the Paul and Penning traps, the orbitrap uses only electrostatic fields to confine and to analyze injected ion populations. In addition, its relatively low cost, simple design and high space-charge capacity make it suitable for tackling complex scientific problems in which high performance is required. This review begins with a brief account of the set of inventions that led to the orbitrap, followed by a qualitative description of ion capture, ion motion in the trap and modes of detection. Various orbitrap instruments, including the commercially available linear ion trap-orbitrap hybrid mass spectrometers, are also discussed with emphasis on the different methods used to inject ions into the trap. Figures of merit such as resolving power, mass accuracy, dynamic range and sensitivity of each type of instrument are compared. In addition, experimental techniques that allow mass-selective manipulation of the motion of confined ions and their potential application in tandem mass spectrometry in the orbitrap are described. Finally, some specific applications are reviewed to illustrate the performance and versatility of the orbitrap mass spectrometers.

Serine sublimes with spontaneous chiral amplification

Sublimation of near-racemic samples of serine yields a sublimate which is highly enriched in the major enantiomer; this simple one-step process occurs under relatively mild conditions, and represents a possible mechanism for the chiral amplification step in homochirogenesis.

Pharmaceutical cleaning validation using non-proximate large-area desorption electrospray ionization mass spectrometry.

Desorption electrospray ionization (DESI) is a droplet-based ionization method that is applied to samples in the ambient environment with little or no sample preparation. Its utility for industrial applications is explored here for the case of pharmaceutical cleaning validation. A non-proximate large-area DESI system was built to examine representative areas of the surfaces of reaction vessels used in active product ingredient (API) manufacturing. A large-area sprayer capable of sampling an area of approximately 2.5 cm(2) was coupled with a transport tube to allow sensitive, representative sampling of APIs from a stainless steel surface 1 m away from the mass spectrometer. The system was used to detect the APIs neostigmine, acebutolol, amiloride, amiodarone, ibuprofen, montelukast, potassium clavulanate, and beta-estradiol, at levels as low as 30-10 ng/cm(2), easily satisfying the general acceptable limits set by the pharmaceutical industry. These levels were achieved from surfaces resembling the equipment used in API manufacturing processes at a rate of 30 s per analysis.

Hand-held mass spectrometer for environmentally relevant analytes using a variety of sampling and ionization methods

A recently developed hand-held, rectilinear ion trap mass spectrometer, capable of performing in situ analysis, has been evaluated for a variety of environmentally relevant analytes. Different sampling and ionization methods were implemented, demonstrating the considerable versatility of this instrument. A discontinuous (viz. pulsed) atmospheric pressure inlet (DAPI) was used to introduce externally-generated analyte ions. Nitro compounds were ionized by electrosonic spray ionization (ESSI) yielding the protonated and sodiated forms of the molecular ion, as well as fragment ions. The amines 2,2,6,6-tetramethylpiperidine, triethylamine and 2,6-diphenylpyridine showed low parts per billion (ppb) detection limits. Vapor phase external ionization was used to examine the chemical warfare simulant dimethyl methylphosphonate and the insect repellant N,N-diethyl-m-toluamide. Membrane introduction mass spectrometry (MIMS) was used as the introduction system for hydrophobic analytes using a selectively permeable (polydimethylsiloxane) membrane placed within the vacuum manifold with subsequent ionization of the thermally desorbed neutral compounds inside the ion trap. MIMS allowed the quantitation of trace levels (a few ppb) of fluorinated compounds in the vapor phase. MIMS was also applied to the quantitation of aqueous polycyclic aromatic hydrocarbons (PAHs) with limits of detection again in the low ppb range for naphthalene, acenaphthene, anthracene and phenanthrene.

Rephasing ion packets in the orbitrap mass analyzer to improve resolution and peak shape

A method is described to improve resolution and peak shape in the Orbitrap under certain experimental conditions. In these experiments, an asymmetric anharmonic axial potential was first produced in the Orbitrap by detuning the voltage on the compensator electrode, which results in broad and multiply split mass spectral peaks. An AC waveform applied to the outer electrode, 180° out of phase with ion axial motion and resonant with the frequency of ion axial motion, caused ions of a given m/z to be de-excited to the equator (z=0) and then immediately re-excited. This process, termed “rephasing,” leaves the ion packet with a narrower axial spatial extent and frequency distribution. For example, when the Orbitrap axial potential is thus anharmonically de-tuned, a resolution of 124,000 to 171,000 is obtained, a 2- to 3-fold improvement over the resolution of 40,000 to 60,000 without rephasing, at 10 ng/µL reserpine concentration. Such a rephasing capability may ultimately prove useful in implementing tandem mass spectrometry (MS/MS) in the Orbitrap, bringing the Orbitrap’s high mass accuracy and resolution to bear on both the precursor and product ions in the same MS/MS scan and making available the collision energy regime of the Orbitrap, ∼1500 eV.