Triple quadrupole methods

For high-throughput analysis, it is important to increase the specihcity of each bioanalytical method. The enhancement of chromatographic resolution presents various limitations. Better selectivity can be obtained with TOF mass analyzers that routinely provide more than 5000 resolution (full width at half-mass or FWHM). The enhanced selectivity of a TOF MS is very attractive for problems such as matrix suppression and metabolite interference. In one report of quantitative analysis using SRM, TOF appeared less sensitive than triple quadrupole methods but exhibited comparable dynamic range with acceptable precision and accuracy.102... 

Sarin and soman have been shown to bind to a tyrosine residue present in a blood protein (51). The precise site of this residue has not yet been confirmed but it is associated with the albumin fraction. An LC/ESI/MS/MS (triple quadrupole) method was developed for its detection after digestion of the albumin fraction with Pronase and clean up on a C18 SPE (solid-phase extraction) cartridge. A... 

There are a variety of possible linked scanning methods, but only those in more frequent use are discussed here. They differ from the linked scanning methods used in triple quadrupole instruments and ion traps in that two of the three fields (V, E, and B) are scanned simultaneously and automatically under computer control. The most common methods are listed in Table 34.1, which also defines the type of scanning with regard to precursor and product ions. 

A further extension of the DFG S19 method was achieved when polar analytes and those unsuitable for GC were determined by LC/MS or more preferably by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Triple-quadrupole MS/MS and ion trap MS" have become more affordable and acceptable in the recent past. These techniques provide multiple analyte methods by employing modes such as time segments, scan events or multiple injections. By improving the selectivity and sensitivity of detection after HPLC separation, the DFG S19 extraction and cleanup scheme can be applied to polar or high molecular weight analytes, and cleanup steps such as Si02 fractionation or even GPC become unnecessary. 

At the present time, LC/MS/MS with triple-quadrupole instruments is the analytical method of choice for the determination of residues of sulfonylurea herbicides. We can expect to see improved triple-quadrupole instrumentation become more available and affordable as time passes, so that more analytical laboratories will have this capability. Time-of-flight (TOP) instrumentation may also play an increasingly important role in sulfonylurea analysis. Even though the metabolites are innocuous, stricter regulatory requirements may mandate that they be monitored, and LC/MS/MS is the method of choice for these compounds also. 

Currently, HPLC/fiuorescence is still the most common technique for the determination of residues of oxime carbamates. With the introduction of ESI and APCI MS interfaces, HPLC/MS analysis for oxime carbamates in various sample matrices has become widespread. However, for a rapid, sensitive, and specific analysis of biological and environmental samples, HPLC/MS/MS is preferred to HPLC/MS and HPLC/fiuorescence. With time, improved and affordable triple-quadrupole mass spectrometers will be available in more analytical laboratories. With stricter regulatory requirements, e.g., highly specific and conclusive methods with lower LOQ, HPLC/MS/MS will be a method of choice for oxime carbamates and their metabolites. 

The results thus show that ammonia DCI-MS/MS using a triple quadrupole mass spectrometer is a convenient method for the detection of additives in PE samples. The softness and selectivity provided by ammonia DCI in combination with the specificity provided by CID, demonstrate great potential for identification of additives directly from PE extracts. The utility of DCI in the quantitative analysis of additives has still to be explored. DCI-MS/MS (B/E) with high collision... 

Selection of a suitable ionisation method is important in the success of mixture analysis by MS/MS, as clearly shown by Chen and Her [23]. Ideally, only molecular ions should be produced for each of the compounds in the mixture. For this reason, the softest ionisation technique is often the best choice in the analysis of mixtures with MS/MS. In addition to softness , selectivity is an important factor in the selection of the ionisation technique. In polymer/additive analysis it is better to choose an ionisation technique which responds preferentially to the analytes over the matrix, because the polymer extract often consists of additives as well as a low-MW polymer matrix (oligomers). Few other reports deal with direct tandem MS analysis of extracts of polymer samples [229,231,232], DCI-MS/MS (B/E linked scan with CID) was used for direct analysis of polymer extracts and solids [69]. In comparison with FAB-MS, much less fragmentation was observed with DCI using NH3 as a reagent gas. The softness and lack of matrix effect make ammonia DCI a better ionisation technique than FAB for the analysis of additives directly from the extracts. Most likely due to higher collision energy, product ion mass spectra acquired with a double-focusing mass spectrometer provided more structural information than the spectra obtained with a triple quadrupole mass spectrometer. 

Mass spectrometric analysis was performed with a hybrid triple quadrupole/ linear ion trap Applied Biosystem MSD Sciex 4000QTRAP (Applied Biosystems, Foster City, USA) instrument equipped with a Turbospray ESI interface. For target quantitative analyses, data acquisition was performed in SRM, recording the transitions between the precursor ion and the two most abundant fragment ions. The developed instrumental method display excellent LODs in SRM mode between 0.5 and 1.2 pg (Table 2). 

Yang, L. et al. 2001. Evaluation of a four-channel multiplexed electrospray triple quadrupole mass spectrometer for the simultaneous validation of LC/MS/MS methods in four different preclinical matrixes. Anal. Chem. 73 1740. 

In a typical analysis, one approach would be to carry out the analysis by first using Cl and quadrupole MS. The fragments from this first MS would then be directed to an El and a TOF mass spectrometer. Different fragments will be observed and this will yield additional information about the sample. In many cases, the MS-MS analysis is applied to samples eluting from either LC, HPLC, or GC chromatographic separation techniques. For additional information on this topic, see Triple Hyphenated Methods. ... 

Personnel Choosing an appropriate technique sometimes comes down to having the right person on your staff to perform the technique. If you, or no one in the lab, had had experience with the hydroxyl value titration, it might not have been an option in the Bulging Drum Problem. Certainly, if the operator of your triple quadrupole mass spectrometer is on vacation and there is no back-up operator, another method, or sending the samples to another lab, may be necessary. Should the method need to be transferred to another lab, does that lab have the requisite people for the job ... 

Liquid chromatography combined with triple-quadrupole mass spectrometers has been used extensively as the analytical method of choice to determine the plasma concentration of compounds. 

---