Triple quadrupole systems

In 1995, when HPLC/MS/MS was becoming the premier tool for PK assays, chromatographic sample cycle times were typically 10 to 12 min. At 10 min per sample, 16 hr were required to process 96 samples. By 2000, scientists used shorter HPLC columns and per-sample cycle times decreased to 5 to 6 min. At 5 min per sample, it takes about 8 hr to assay one 96-well plate of samples. As a result, parallel HPLC became popular Korfmacher et al.154 described a two-column system and an MS vendor produced a triple quadrupole system designed to work with four HPLC columns.16155-158 Advances in fast chromatography continued and by 2005, sample cycle times of 1 to 2 min became common.21 87 159-161 At 2 min per sample, 3 hr are required to assay one 96-well plate of samples. 

At present, the most powerful and promising interfaces for drug residue analysis are die particle-beam (PB) interface that provides online EI mass spectra, the thermospray (TSP) interface diat works well with substances of medium polarity, and more recently the atmospheric pressure ionization (API) interfaces that have opened up important application areas of LC to LC-MS for ionizable compounds. Among die API interfaces, ESP and ISP appear to be the most versatile since diey are suitable for substances ranging from polar to ionic and from low to high molecular mass. ISP, in particular, is compatible with the flow rates used with conventional LC columns (70). In addition, both ESP and ISP appear to be valuable in terms of analyte detectability. These interfaces can further be supplemented by preanalyzer collision-induced dissociation (CID) or tandem MS as realized with the use of triple quadrupole systems. Complementary to ESP and ISP interfaces with respect to the analyte polarity is APCI with a heated nebulizer interface. This is a powerful interface for both structural confirmation and quantitative analysis. 

Tandem mass spectrometers are either triple quadrupole systems (the collision cell is also a quadrupole) or quadrupole ion-trap spectrometers. A triple quadrupole mass spectrometry system is shown in Figure 32F-2. Here, the first quadrupole acts as a mass filter to select the ion of interest. This ion is then fragmented by collision with an inert gas in the collision cell. The final quadrupole mass analyzes the fragments produced. The triple quadrupole system can be operated in other modes. For example, if the first quadrupole is operated as a wide mass filter to transmit a wide range of ions and no collision gas is present in the collision cell, the instrument is operating as an LC/MS system. The instrument can be operated by scanning one or both quadrupoles to produce mass spectra of the fragments of ions selected by the first quadrupole as that quadrupole is scanned. 

Lor analyses, two sets of HPLC conditions were used, depending on whether UV (285 nm) or MS (electrospray ionization on a triple quadrupole system) was to be used for detection. Lor MS detection, analyses were conducted using a 125 x 4 mm (5 pm) Lichrospher 60 RP-Select B column. Eluent A was 800 ml water/200ml acetonitrile/3.08 g ammonium acetate adjusted to pH 6.5 with acetic acid. Eluent B was 500 ml water/500ml acetonitrile/1.93 g ammonium acetate adjusted to pH 6.5 with acetic acid. The gradient was run at 0.5ml/min as follows from 0-25.0 min, 100% A from 25.0-35.0 min, 100% A-100% B from 35.0-45.0 min, 100% B from... 

A recent study investigated the effects of matrix interferences on the analytical performance of a LC-MS/MS triple quadrupole system for the determination of acidic herbicides in water. Salinity provided a dramatic decrease in response for early eluting compounds, but LC-LC coupled column configuration efficiently eliminated the matrix effect. This approach of LC-LC-ESI-MS/MS using a Supelco ABZ -h (amide modified) as a second column was the most favorable as regards matrix effects, with reliable quantification of herbicides at the level 0.4 ixg/l ... 

For some complex mixtures, the combination of LC and MS does not provide enough resolution. In recent years it has become feasible to couple two or more mass analyzers to form tandem mass spectrometers (see Section 20C--S). When combined with LC, the tandem mass spectrometry system is called an LC/MS/MS instrument. Tandem mass spectrometers are usually triple quadrupole systems or quadrupole ion-trap spectrometers. To attain higher resolution than can be achieved with a quadrupole, the final mass analyzer in a tandem MS system can be a time-of-flight mass spectrometer. Sector mass spectrometers can also be combined to give tandem systems. Ion cyclotron resonance and ion-trap... 

The triple quadrupole system consists basically of two quadrupole analysers (first and second quadrupole). The second quadrupole has only an R.F. voltage (without the D.C. component) and serves therefore as an ion focusing device [7]. The collision cell is located between the rods of this quadrupole. It has been found that when doing MS/MS with a tandem quadrupole mass analyser, an additional quadrupole focusing device is needed to focus the ions formed in the collision cell. 

Where tandem mass spectrometry is available, even more security can be achieved by use of selected reaction monitoring (SRM) instead of SIM. Tandem mass spectrometry is the use of successive steps of MS to select or scan ions, create fragments from them, and scan the fragments. It can be carried out in time or space. Triple quadrupole systems are an example of tandem-in-space. The masses of parent ions are filtered and scanned by the first quadrupole, fragmentation occurs in the... 

H. Javaheri, Y. Le Blanc, B. A. Thomson, J. Fernandez de la Mora, J. Rus, and J. A. Sillero-Sepulveda, Analytical characteristics of a differential mobility analyzer coupled to a triple quadrupole system (DMA-MSMS), Poster 061, Annual ASMS conference, 1-6 June, Denver, Colorado, 2008. 

In neutral loss scan, all precursor ions, which lose a particular neutral particle (that otherwise cannot be detected in MS), are detected. Both mass analysers scan, but with a constant selected mass difference, which corresponds to the mass of the neutral particle lost. This analysis technique is particularly meaningful if molecules contain the same functional groups (e.g., metabolites as acids, glucuronides or sulfates). In this way, it is possible to identify the starting ions which are characterized by the loss of a common structural element. Both MS/MS scan techniques can be used for substance-class-specific detection in triple quadrupole systems. Ion trap systems allow the mapping of these processes by linking the scans between separate stages of MS in time. 

Figure 2.236 Curved collision cell of a triple quadrupole system (90°) for reduction of nonspecific noise by eliminating neutral particles and photons from the ion flight path. (TSQ Quantum series, courtesy Thermo Fisher Scientific.)...

Liu, Y.-M., Akervik, K. and Maljers, L. (2006) Optimized high resolution SRM quantitative analysis using a calibration correction method on a triple quadrupole system. ASMS 2006 Poster Presentation, TP08, 115. 

The mass spectrometric detection in this application is achieved by MS/MS using an ion trap mass spectrometer providing excellent selectivity and sensitivity for trace-level quantitation in environmental water samples. Alternatively a triple quadrupole system can be employed using a similar setup. Highest selectivity and lowest determination levels have been achieved also by using high-resolution mass spectrometer (De Boer et al, 2001 Krumwiede, 2006). 

This symbol refers to multistage MS/MS experiments designed to record product ion spectra where n is the number of product ion stages (fragment ions). For ion traps, sequential MS/MS experiments can be undertaken where n>2 whereas for a simple triple quadrupole system n = 2, -> Multiple-stage mass spectrometry. 

MS/MS can be carried out with a triple quadrupole system such as that shown in Figure 8. A first mass analysing quadrupole, Q1 mass selects a precursor ion from the ESI source. The ion enters the collision cell with energies typically 10-500 eV. Here... 

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