Ionspray mass spectrometry, a well established organic analysis technique, has been coupled to high-performance liquid chromatography for speciation of organic arsenic compounds. The ionspray source and differentially pumped interface of the mass spectrometer were operated in dud modes for elemental and molecular analysis. Tandem mass spectrometry was employed to increase selectivity. Dual mode detection was applied to demonstrate the utility of the technique for analysis of nine organoarsenic standards, including four dimethylarsinylriboside derivatives (arsenosugars). Structural fragmentation patterns showing molecular dissociation through an expected common product ion were obtained for the four arsenosugars. Molecular mode detection was utilized for qualitative verification of speciation analysis by high-performance liquid chromatography coupled to inductively coupled plasma mass spectrometry of organoarsenicals in plaice and for analysis of an arsenosugar in extracts of oyster and mussel.

In this work, a high repetition rate laser matrix-assisted laser desorption/ionization (MALDI) source is studied on a quadrupole-time-of-flight (QqTOF) and a triple quadrupole (QqQ) mass spectrometer for rapid quantification of small pharmaceutical drugs. The high repetition rate laser allows an up to 100-fold higher pulse frequency as compared with regular MALDI lasers, resulting in much larger sample throughput and number of accumulated spectra. This increases the reproducibility of signal intensities considerably, with average values being around 5% relative standard deviation after taking into account the area ratio of the analyte to an internal standard. Experiments were conducted in MS/MS mode to circumvent the large chemical background due to MALDI matrix ions in the low mass range. The dynamic range of calibration curves on the QqTOF mass spectrometer extended over at least two orders of magnitude, whereas on the QqQ it extended over at least three orders of magnitude. Detection limits ranged from 60-400 pg/microL on the QqTOF and from 6-70 pg/microL on the QqQ for a series of benzodiazepines. The benzodiazepine content of commercial pill formulations was quantified, and less than 5% error was obtained between the present method and the manufacturer's certified values. Furthermore, a high sample throughput was achieved with this method, so that a single MALDI spot could be quantitatively scanned in as little as 15 s, and an entire 96-well MALDI plate in 24 min.

The usefulness of MALDI for small-molecule work has been limited by matrix chemical interference in the mass range of interest, tedious sample preparation, and various crystallization and sample deposition issues. We report instrument characterization and small-molecule quantification performance data from a high repetition rate laser MALDI ion source coupled to a triple quadrupole mass spectrometer. The high repetition rate laser improves sensitivity and precision and allows a proportional increase in sample throughput. Tandem mass spectrometry is used to discriminate the signal from the high chemical background caused by the MALDI matrix. Successful quantification requires use of an internal standard and a means of sample cleanup for typical in vitro sample compositions. This instrument combination and analysis technique is relatively insensitive to sample crystal quality and spot homogeneity. Quantitative performance results are characterized for 53 small-molecule pharmaceutical compounds and compared to those obtained by ESI-MS/MS. Further comparison between MALDI and ESI is examined, and the potential for high-throughput MALDI-MS/MS quantification is demonstrated.

CollsionaUy activated dissociation ei€tciency and fragment ion mass resolution have been characterized on a triple quadrupole mass spectrometer equipped with an enclosed collision cell which is operated at relatively high pressure. The higher pressure results in improved efficiency (and therefore improved ion transmission) and better mass resolution than has been obtained previously with collision cells operated at lower pressure. Efficiencies of 30-50%, measured as the fractions of original precursor ion in Q l which are detected as resolved fragment ions, are typical for singly charged ions, compared with 5-10% achieved previously. Mass resolution of fragment ions is improved to the point that the isotopes from quadruply charged fragment ions can be resolved.A typical triple quadrupole mass spectrometer (MS/MS) system' consists of two resolving quadrupole mass filters (Q1 and Q3) separated by another quadrupole assembly (Q2) into which a collision gas can be introduced to allow collisionally activated dissociation (CAD) in the radio frequency (rf) field. In an MS/ (9) Lemoine, J. L.; Fournet, B.; Despeyroux, D.; Jennings, IC R; Rosenberg, (10) Zirrolli, J. Abstract published in

A MALDI ion source on a triple quadrupole mass spectrometer constructed for the purpose of obtaining high speed quantitative measurements on drugs and other low molecular weight compounds is described. Particular attention is given to the ion generation and transport phenomena that affect analysis speed, throughput, and practical instrument robustness. In this regard parameters that affect desorption speed, beam spreading, ion flight times, sensitivity, signal-to-noise, ion fragmentation, sample carry-over, and instrument contamination are examined and experimental results are provided. MALDI and electrospray sensitivity is compared, to provide a practical frame of reference. . One interesting configuration is MALDI on a triple quadrupole (QqQ) designed for the express purpose of acquiring rapid quantitative measurements on drug entities and other low molecular weight compounds dried and arrayed on microtiter plates. The concept is analogous to plate readers used in high throughput screening albeit these optical based systems derive their speed from parallel measurements. In the case of a mass spectrometer the analysis is inherently serial in nature but could be operated at rates that would approach the throughputs of the optical systems. Assessments of the general utility of MALDI TOF for small molecule quantitative and qualitative analyses have been reported [2] and reviewed [3]. Studies of the practicality of the triple quadrupole approach for various applications have begun to appear in the literature using prototype triple quadrupole instruments [4,5], which have examined in detail the quantitative figures of merit of the technique in biological samples, emphasizing the importance of the use of internal standards. In a sister publication to this work [4], issues important to quantitation and general analytical utility such as chemical diversity, background produced by blank measurements, and s/n are covered in detail. The focus of this work are the characteristics of the instrumentation.The reasons why a triple quadrupole is a logical choice for a MALDI based high speed quantitation tool will be elaborated on in this paper but can be summarized as follows. MALDI on a triple quadruple decouples the synchronization of the desorption event with the mass analysis, similar to orthogonal MALDI TOF, but quite distinct from traditional low-pressure MALDI TOF. The mass spectrometer performance is thus independent from the sample morphology. This allows target preparation to be a noncritical issue so inhomogeneities in the sample, as would be expected in any high throughput methodology, will have no effect on the mass spectrometer mass resolution or accuracy. High-pressure operation of the source and the preanalyzer RF optics is readily accommodated in a QqQ. Collisional cooling of the ion beam is achieved at higher pressures, which reduces ion fragmentation and allows a broader range of laser energy to be utilized. With low-pressure operation on TOF instruments the laser energy must be kept low, near the ionization ...