Tandem chromatographic methods

Comparison of CPC Spin Column/HPLC ESI-MS with Tandem Chromatographic Method of CPC/HPLC ESI-MS... 

In principle, the analytical results obtained by the GPC spin column/HPLC ESI-MS methodology described in this chapter should be similar to the results obtained using the tandem chromatographic method of GPC/reversed-phase HPLC ESI-MS described in Chapter 3. There are practical advantages for each method. Since each of the chromatographic and mass spectral steps are done serially for the GPC spin column/HPLC ESI-MS methodology, each of the steps can be performed and optimized individually. In the event of mass spectrometer failure, the production of spin column eluate samples can proceed and samples can be stored for future analysis. In contrast, the parallel methodology of tandem GPC/ reversed-phase HPLC ESI-MS requires the simultaneous optimization of multi-... 

Ethylenethiourea (ETU) is a toxic decomposition product/metabolite of alky-lenebis(dithiocarbamates). This compound could be generated during processing of treated crops at elevated temperature. Different chromatographic methods to determine the residue levels of ETU have been published. After extraction with methanol, clean-up on a Gas-Chrom S/alumina column and derivatization (alkylation) with bro-mobutane, ETU residues can be determined by GC with a flame photometric detector in the sulfur mode. Alternatively, ETU residues can also be determined by an HPLC method with UV detection at 240 nm or by liquid chromatography/mass spectrometry (LC/MS) or liquid chromatography/tandem mass spectrometry (LC/MS/MS) (molecular ion m/z 103). ... 

Traditional methodologies for structural identification of trace level impurities in drng substances/products usually involve fractionation of each impurities using a scaled-np analytical chromatographic method, followed by off-line spectroscopic analysis. Coupling of HPLC separation and electrospray mass spectrometry allows on-line acquisition of full scan mass spectra and generation of tandem mass spectrometric data. LC/ESI MS has revolntionized trace analysis for qnalitative and quantitative studies in pharmaceutical analysis. 

As noted earlier, the development of the dual cell (37), tandem quadrupole-FTMS (46, 47) and external ionization cell (48, 49) has facilitated the coupling of FTMS and chromatographic methods. Advances in interfacing separation techniques with FTMS will be important in the analysis of mixtures, especially where high mass resolution is required. For example, liquid chromatographic introduction of mixtures isolated from biological systems directly into an FTMS for analysis would eliminate the need for laborious sample clean up. 

Constanzer, M. Chavez, C. Matuszewski, B. Development and comparison of high-performance liquid chromatographic methods with tandem mass spectrometric and ultraviolet absorbance detection for the determination of cyclobenzaprine in human plasma and urine. J.Chromatogr.B, 1995, 666, 117-126... 

Molecular weight distribution information obtained by size-exclusion chromatography on its own is insufficient to characterize the properties of complex polymers, such as copolymers and block and graft polymers [23,514,524]. For these polymers the chemical composition and functionality type distributions are equally important. A major obstacle to the characterization of these materials is that their molecular properties are present as joint distributions. Unlike the mass distribution the composition and functionality distributions can only be determined by separation methods that employ interactions with the stationary phase. To fully characterize a complex polymer it is not unusual to use manual or automated tandem techniques where the sample is fractionated according to its chemical or end group composition for subsequent further separation by size-exclusion chromatography to establish their mass distribution. Chromatographic methods may also be combined with spectroscopic methods to determine microstructural information. 

For some complex mixtures the combination of GC or LC and MS does not provide enough resoluiitin. In recent years, ii has become feasible to couple chromatographic methods with tandem mass spectrometers lo form GC / MS / MS and I. C / MS / MS systems.- There have also been reports of LC/MS" instruments. 

The commonly used methods for the determination of these drugs are immunoassays and chromatography. Most immunoassays for immunosuppressants are semiautomated since extraction of drugs from the whole blood is needed before analysis. Immunoassays are convenient due to automation, but have problems with cross-reactivity with drug metabolites (3, 6). Both polyclonal and monoclonal antibody-based assays are available. Monoclonal antibody-based immunoassays are more specific. HPLC with ultraviolet detection and tandem mass spectrometry are commonly used chromatographic methods for the assay of immunosuppressants. Due to their specificity and sensitivity, tandem mass spectrometry assays are preferred and are now in wide use (7, 8). The other major advantage of tandem mass spectrometry assays is their ability to simultaneously measure several immunosuppressants (7-10). Pharmacokinetic properties of CSA, sirolimus, and tacrolimus are shown in Table 1 (3, 6, 11). 

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