Coupling of ion-molecule reactions with liquid chromatography on a quadrupole ion trap mass spectrometer

We report for the first time a coupling of gas-phase ion-molecule reactions with chromatographic separations on a quadrupole ion trap mass spectrometer. The interface was accomplished by using a pulsed valve for the introduction of a volatile neutral into the ion trap. The pulsed valve controller is synchronized with the mass spectrometer software. The setup requires some minor modifications to the vacuum system of the commercial quadrupole ion trap but most of the modifications are external to the mass spectrometer. Two applications of this interface are described: differentiation between two phosphoglucose positional isomers and detection of a phosphopeptide in a peptide mixture. Both applications are using the reactivity of trimethoxyborate towards a phosphate moiety in the negative ion mode. The detection of phosphopeptides hinges on our findings that non-phosphorylated peptide anions do not react with trimethoxyborate. This LC/MS detection can be easily visualized in terms of selected reaction monitoring.     

Analysis of volatiles and semivolatiles in drinking water by microextraction and thermal desorption

A new technique to analyze aqueous samples for nanograms per liter levels of volatile and semivolatile compounds using microextraction and thermal desorption into a gas chromatograph/ion trap mass spectrometer (GC/MS) is described. This method is inherently sensitive (50 mL of aqueous sample is extracted prior to each desorption), uses no solvents, and detects volatiles and semivolatiles in the same analysis. Aqueous standards and environmental samples are pumped through a length of porous-layer open-tubular capillary column, which is then thermally desorbed onto a 30 m × 0.25 mm i.d. analytical column interfaced to an ion trap mass spectrometer for subsequent separation and detection. Sharp chromatographic peaks and reproducible retention times (RT) were observed. Replicate injections of surrogates (n = 6) averaged 32.6% R.S.D. Analysis of domestic tap water detected 55 analytes, some at the low-nanograms per liter level, and detected 3 halogenated ethenes, not previously reported in drinking water. Analysis of an aqueous sample from a municipal ground water source detected the presence of numerous semivolatile compounds at trace-levels.     

Optimisation of ion trap parameters for the quantification of chlormequat by liquid chromatography/mass spectrometry and the application in the analysis of pear extracts

Optimisation of the activation parameters for ion trap mass spectrometric analysis of the chlormequat cation using simplex optimisation enabled the product ion (m/z 58) response to be improved 1000-fold. A comparison of the sensitivity of the optimised ion trap mass spectrometer with that of a triple quadrupole mass spectrometer for liquid chromatography/tandem mass spectrometry (LC/MS/MS) showed that similar limits of detection (LODs) could be achieved. For the MS/MS transition of the (35)Cl precursor to the most abundant product, LODs were 0.8 ng cation mL(-1) (0.004 mg cation kg(-1) pear equivalent) and 1.0 ng cation mL(-1) (0.005 mg cation kg(-1) pear equivalent) on the triple quadrupole and ion trap instrument, respectively.     

Screening of drugs in equine plasma using automated on-line solid-phase extraction coupled with liquid chromatography–tandem mass spectrometry

A rapid liquid chromatography–tandem mass spectrometry (LC–MS–MS) method was developed for the simultaneous screening of 19 drugs of different classes in equine plasma using automated on-line solid-phase extraction (SPE) coupled with a triple quadrupole mass spectrometer. Plasma samples were first protein precipitated using acetonitrile. After centrifugation, the supernatant was directly injected into the on-line SPE system and analysed by a triple quadrupole LC–MS–MS in positive electrospray ionisation (+ESI) mode with selected reaction monitoring (SRM) scan function. On-line extraction and chromatographic separation of the targeted drugs were performed using respectively a polymeric extraction column (2 cm L × 2.1 mm ID, 25 μm particle size) and a reversed-phase C18 LC column (3 cm L × 2.1 mm ID, 3 μm particle size) with gradient elution to provide fast analysis time. The overall instrument turnaround time was 9.5 min, inclusive of post-run and equilibration time. Plasma samples fortified with 19 targeted drugs including narcotic analgesics, local anaesthetics, antipsychotics, bronchodilators, mucolytics, corticosteroids, sedative and tranquillisers at sub-parts per billion (ppb) to low parts per trillion (ppt) levels could be consistently detected. No significant matrix interference was observed at the expected retention times of the targeted ion transitions. Over 70% of the drugs studied gave detection limits at or below 100 pg/mL, with some detection limits reaching down to 19 pg/mL. The method had been validated for extraction recovery, precision and sensitivity, and a blockage study had also been carried out. This method is used regularly in the authors’ laboratory to screen for the presence of targeted drugs in pre-race plasma samples from racehorses.     

Scandium dipivaloyl methanate as a volatile precursor for thin film deposition

The coupling of a quadrupole mass spectrometer (QMS) via a heated capillary to a commercial thermogravimetric analyser is described. The amu and temperature ranges available were up to 1000 amu and 1500°C, respectively. The system was evaluated with test compounds, yielding gaseous species in the m/z range of 17-80, and then used for the study of thermal behaviour of scandium dipivaloyl methanate or Sc(thd)₃ which is discussed in detail. Sc(thd)₂ appears as the major Sc-containing species with m/z=411 in the gas phase at 200-300°C.This revised version was published online in November 2005 with corrections to the Cover Date.     

Comparison of electron ionization mass spectra of some organic compounds (MW < 200 Da) recorded on mass spectrometers of various types

Low-resolution electron ionization mass spectra recorded on various types of mass spectrometers (time-of-flight, quadrupole, and three-dimensional ion trap) were compared. A model mixture of 10 organic compounds (MW < 200 Da) was analyzed by gas chromatography-mass spectrometry. Pure mass spectra of analytes were extracted using the AMDIS software. The best repeatability was achieved for the time-of-flight mass spectrometer. The mass spectra recorded by a quadrupole and a time-of-flight mass spectrometer were quite similar. In the case of these instruments, library search using a commercial mass spectral data base (NIST’05) gave satisfactory result for each analyte (rank 1 or 2 in the “hit list”; Match > 900). In some cases, the mass spectra of model compounds recorded by the ion trap mass spectrometer differed in intensity of certain mass spectral peaks (but not in the set of peaks) from the mass spectra presented in the library and from the experimental mass spectra recorded by the time-of-flight and quadrupole instruments.     

Trace level analysis of polycyclic aromatic hydrocarbons in surface waters by solid phase extraction (SPE) and gas chromatography-ion trap mass spectrometry (GC-ITMS).

Ontario Provincial Water Quality Objectives for polycyclic aromatic hydrocarbons (PAHs) in surface waters require low parts per trillion (ng L(-1))/high parts per quadrillion (pg L(-1)) detection limits. To meet these monitoring requirements, a solid phase extraction-gas chromatography-ion trap mass spectrometry (SPE-GC-ITMS) method was developed. Seventeen priority PAHs commonly monitored in surface and drinking waters were examined using an external ionization ion trap mass spectrometer operated in selected ion monitoring (SIM) mode. Under 70 eV electron ionization (El) conditions, both the quantitative [M]+* ion and confirmatory [M - 2H]+* ion were formed in classical abundance ratios. Each of these ion species was isolated in the ion trap using a specific scan function. However, to overcome poor levels of confirmatory ion abundance which otherwise restrict PAH method detection limits (MDLs), the abundance of [M - 2H]+* ions was augmented during isolation by causing the dissociation of [M]+* with the broad-band waveform used for high mass ion ejection. Augmenting the [M - 2H]+* signal intensity facilitated the achievement of MDLs of approximately 1 ng L(-1). PAHs in surface water samples that were not detected by current Ontario Ministry of the Environment high-performance liquid chromatography (HPLC)-fluorescence and GC-single-stage quadrupole mass spectrometry methods were detected and quantified using the ion trap mass spectrometry SIM method. The data produced by all three methods on natural water samples fortified at sub-parts per billion (ppb) levels were comparable. When applied to Standards Council of Canada/Canadian Association for Environmental Analytical Laboratories (SCC/CAEAL, www.CAEAL.ca) accreditation audit samples, the SPE-GC-ITMS method results met all performance evaluation criteria.     

Transmission mode ion/ion reactions in the radiofrequency‐only ion guide of hybrid tandem mass spectrometers

Transmission mode ion/ion reactions have been performed within the first quadrupole, the Q0 radiofrequency (RF)‐only quadrupole, of two types of hybrid tandem mass spectrometers (viz., triple quadrupole/linear ion trap and QqTOF instruments). These transmission mode reactions involved the storage of either the reagent species and the transmission of the analyte species through the Q0 quadrupole for charge inversion reactions or the storage of the analyte ions and transmission of the reagent ions as in charge reduction experiments. A key advantage to the use of transmission mode ion/ion reactions is that they do not require any instrument hardware modifications to provide interactions of oppositely charged ions and can be implemented in any instrument that contains a quadrupole or linear ion trap. The focus of this work was to investigate the potential of using the RF‐only quadrupole ion guide positioned prior to the first mass‐resolving element in a tandem mass spectrometer for ion/ion reactions. Two types of exemplary experiments have been demonstrated. One involved a charge inversion reaction and the other involved a charge reduction reaction in conjunction with ion parking. Ion/ion reactions proved to be readily implemented in Q0 thereby adding significantly greater experimental flexibility in the use of ion/ion reaction experiments with hybrid tandem mass spectrometers. Copyright © 2009 John Wiley & Sons, Ltd.     

Product ion scanning using a Q-q-Q linear ion trap (Q TRAP) mass spectrometer

The use of a Q-q-Q(linear ion trap) instrument to obtain product ion spectra is described. The instrument is based on the ion path of a triple quadrupole mass spectrometer with Q3 operable as either a conventional RF/DC quadrupole mass filter or a linear ion trap mass spectrometer with axial ion ejection. This unique ion optical arrangement allows de-coupling of precursor ion isolation and fragmentation from the ion trap itself. The result is a high sensitivity tandem mass spectrometer with triple quadrupole fragmentation patterns and no inherent low mass cut-off. The use of the entrance RF-only section of the instrument as accumulation ion trap while the linear ion trap mass spectrometer is scanning enhances duty cycles and results in increased sensitivities by as much as a factor of 20. The instrument is also capable of all of the triple quadrupole scans including multiple-reaction monitoring (MRM) as well as precursor and constant neutral loss scanning. The high product ion scanning sensitivity allows the recording of useful product ion spectra near the MRM limit of quantitation.     

Orthogonal trap time-of-flight mass spectrometer using a collisional damping chamber

We report a new hybrid mass spectrometer, which is a combination of a quadrupole ion trap and an orthogonal time-of-flight (TOF) mass spectrometer. This new configuration consists of a collisional-damping chamber (CDC) inserted between an MSn-capable ion trap and a high-mass-accuracy orthogonal-TOF mass spectrometer. Because the CDC converted an ion packet into an energy-focused and quasi-continuous beam, a high mass resolution of over 10,000 and a high mass accuracy of better than 3 ppm were achieved. Moreover, the ratio of the maximum detectable m/z to the minimum detectable m/z, which is referred to here as the mass window, was improved to more than 10.     

Calibration function for the orbitrap FTMS accounting for the space charge effect

Ion storage in an electrostatic trap has been implemented with the introduction of the Orbitrap Fourier transform mass spectrometer (FTMS), which demonstrates performance similar to high-field ion cyclotron resonance MS. High mass spectral characteristics resulted in rapid acceptance of the Orbitrap FTMS for Life Sciences applications. The basics of Orbitrap operation are well documented; however, like in any ion trap MS technology, its performance is limited by interactions between the ion clouds. These interactions result in ion cloud couplings, systematic errors in measured masses, interference between ion clouds of different size yet with close m/z ratios, etc. In this work, we have characterized the space-charge effect on the measured frequency for the Orbitrap FTMS, looking for the possibility to achieve sub-ppm levels of mass measurement accuracy (MMA) for peptides in a wide range of total ion population. As a result of this characterization, we proposed an m/z calibration law for the Orbitrap FTMS that accounts for the total ion population present in the trap during a data acquisition event. Using this law, we were able to achieve a zero-space charge MMA limit of 80 ppb for the commercial Orbitrap FTMS system and sub-ppm level of MMA over a wide range of total ion populations with the automatic gain control values varying from 10 to 10⁷.     

Controlled ion fragmentation in a 2-D quadrupole ion trap for external ion accumulation in ESI FTICR mass spectrometry

Undesired fragmentation of electrospray generated ions in an rf multipole traps can be problematic in many applications. Of special interest here is ion dissociation in a 2-D quadrupole ion trap external to a Fourier transform ion cyclotron resonance mass spectrometer (FTICR MS) used in proteomic studies. In this work, we identified the experimental parameters that determine the efficiency of ion fragmentation. We have found that under the pressure conditions used in this study there is a specific combination of the radial and axial potential well depths that determines the fragmentation threshold. This combination of rf and dc fields appears to be universal for ions of different mass-to-charge ratios, molecular weights, and charge states. Such universality allows the fragmentation efficiency of the trapped ions in the course of capillary liquid chromatography (LC) separation studied to be controlled and can increase the useful duty cycle and dynamic range of a FTICR mass spectrometer equipped with an external rf only 2-D quadrupole ion trap.     

四极离子阱数字式共振激发控制技术的研发与应用

共振激发控制技术是提高四极离子阱分辨率、灵敏度,实现其多级质谱分析的关键技术。针对质谱仪小型化趋势,提出基于现场可编程门阵列(filed-programmable gate array,FPGA)软件实现直接数字合成器(direct digital synthesizer,DDS)信号幅度调制的方法,开发出数字式共振激发控制技术,研制出结构更简单的共振激发控制系统。在对性能要求较高的电喷雾离子源-矩形离子阱质谱仪中,应用这套系统实现了单质荷比选择离子、三级质谱分析和600~2000 Thomson质荷比范围的全扫描等功能。相比使用模拟技术实现幅度调制的控制单元,数字式共振激发控制单元的功耗只有其10%,系统性能也满足四极离子阱的需求。     

On-line coupling of liquid chromatography,capillary gas chromatography and mass spectrometry for the determination and identification of polycyclic aromatic hydrocarbons in vegetable oils

Summary An on-line combination of liquid chromatography, gas chromatography and mass spectrometry has been realized by coupling a quadrupole mass spectrometer to an LC-GC apparatus. Liquid chromatography was used for sample pretreatment of oil samples of different origin. The appropriate LC fraction, containing polycyclic aromatic hydrocarbons, was transferred to the gas chromatograph using a loop-type interface. After solvent evaporation through the solvent vapour exit and subsequent GC separation, the compounds were introduced into the mass spectrometer for detection and identification. The GC column was connected to a short piece of deactivated fused silica that protruded into the ion source. The total analytical set-up allowed the direct analysis of oil samples after dilution in n-pentane without any sample clean-up. Detection limits are about 40 pg in the full scan mode and about 1 pg with selective ion monitoring, i.e. 20 ppb and 0.5 ppb respectively.     

A new integrated system for simultaneous TG-DTA-MASS spectrometry

A new integrated TG-DTA-MS system is described based upon a simultaneous TG-DTA unit coupled to a 200 amu range microprocessor controlled quadrupole mass spectrometer. An inert sampling facility and bakeable dual inlet system allow runs to be performed in a wide range of atmospheres, at temperatures up to 1500°C.     

Ion trap mass spectrometry: a personal perspective

This paper is a personal perspective of the commercial development of the three-dimensional quadrupole ion trap mass spectrometer. Early ion trap invention and development which dates back to 1953, is described. The development of the ion trap is traced through three ages with the last age being where commercial development takes place. Key technical breakthroughs in ion trap technology and commercialization are presented and described up to the present time.     

Profiling of 19-norsteroid sulfoconjugates in human urine by liquid chromatography mass spectrometry

19-Nortestosterone (nandrolone) major metabolites in human urine are excreted as sulfoconjugated and glucuroconjugated forms. A sensitive and selective liquid chromatography/tandem mass spectrometry (LC/MS/MS) method in negative ESI mode was developed for direct quantification of 19-norandrosterone sulfate (19-NAS) and 19-noretiocholanolone sulfate (19-NES). For both sulfoconjugates, the [M−H]⁻ ion at m/z 355 and the fragment ion at m/z 97 were used as the precursor and product ions, respectively. The purification method involved a complete and rapid separation of sulfates and glucuronides in two extracts after loading the sample on a weak anion exchange solid phase extraction support (SPE Oasis^® WAX). Then, sulfates were separated by LC (Uptisphere^® ODB, 150 mm × 3.0 mm, 5 μm) and analyzed on a linear trap and a triple quadrupole mass spectrometer. The lower limit of detection (LLOD) and lowest limit of quantification (LLOQ) were of 100 pg mL⁻¹ and 1 ng mL⁻¹, respectively. Assay validation demonstrated good performances in terms of trueness (92.0-104.9%), repeatability (0.6-7.2%) and intermediate precision (1.3-10.8%) over the range of 1-2500 ng mL⁻¹. Finally, 19-NAS and 19-NES in urine samples collected after intake of 19-norandrostenedione (nandrolone precursor) were quantified. This assay may be easily implemented to separate glucuronide and sulfate steroids from urine specimens prior to quantification by LC/MS/MS.     

Characterization of bioparticles using a miniature cylindrical ion trap mass spectrometer operated at rough vacuum

A miniature cylindrical ion trap mass spectrometer (CIT-MS) equipped with an inexpensive mechanical pump was constructed, and used to measure the masses of cells and microparticles generated by laser induced acoustic desorption ionization. Compared with a previous lab scale quadrupole ion trap mass spectrometer (QIT-MS), the novel miniature CIT-MS had smaller volume (the radius r(0)=5 mm), simpler ion trap fabrication and overall instrument construction, required a lower trapping voltage, and reduced the weight, power and cost of the instrument. The CIT-MS was calibrated using standard polystyrene beads of 2.982 μm diameter. The CIT-MS was used to measure the total dry weight of human red blood cells (RBCs) from a healthy female adult (2.12×10(13) Da) and a patient with anemia (1.35×10(13) Da). The coefficient of variance (CV) for the healthy individual was 21% and that for the patient was 30.4%. The CIT-MS was also applied to guinea pig RBCs and the total dry weight was determined as 1.34×10(13) Da with a CV of 37.9%. These measurements are consistent with previous QIT-MS measurements. The new miniaturized instrument has potential for applications in field-portable, biological and aerosol analysis.     

Coupling of hydrodynamically closed large bore capillary isotachophoresis with electrospray mass spectrometry

Capillary isotachophoresis with coupled columns provides efficient means for rapid electrophoretic analysis of sample volumes of up to 10 μl or more. Commercially available instruments are commonly equipped with conductivity and UV absorbance detectors; however, their on-line coupling with electrospray mass spectrometry is highly desirable. In this work we have modified the commercial coupled column isotachophoresis system for direct connection to an ion trap mass spectrometer. The design included attachment of an elution block with a short capillary transfer line directing the separated zones towards the mass spectrometer. The modification further included separation of the injection and electrode blocks from the separation columns by semipermeable membranes eliminating unwanted fluid movements in the wide bore fluoropolymer separation capillaries. Fused silica capillaries with varying internal diameter were connected as a transfer line between the elution block and mass spectrometer. The transfer line served also as the ESI tip of the sheathless electrospray interface. During the analysis the first, wide bore preseparation capillary with 0.8 mm internal diameter served for removal of the bulk sample components and preseparation of the potentially interfering analytes. After the electronic column switching the separation was finished in a 0.3 mm internal diameter capillary and the separated ITP zones were transferred in-line by a spray liquid towards the mass spectrometer. The instrumentation was tested for determination of vitamins in whole blood analysis and separation of tryptic peptides.