Orthogonal extraction applications

Orthogonal extraction, improvements in TOF/MS resolution, and improvements in electronics have created a new application for TOF/MS in accurate mass measurements [70,71]. Accurate mass applications have traditionally been associated with high-resolution magnetic sector and FTMS systems. The ability to provide accurate mass measurements (+5 ppm) with more cost-effective instrumentation has created potential opportunities in the pharmaceutical industry. Such applications can offer improved selectivity for single-stage instrumentation and metabolite or impurity/degradation product identification, particularly when standard compounds are not available, such as in early drug discovery. 

Sometimes orthogonal offline SPE steps were used prior to online SPE LC/MS/MS. These preparation steps were used to remove interference and concentrate samples. In an application to measure urinary N7-(benzo[a]pyren-6-yl)guanine (BP-6-N7Gua), a biomarker for exposure to polyaromatic hydrocarbons (PAHs), a two-step offline SPE was first performed using Sep-Pak C8 (Waters, Milford, Massachusetts) and Strata SCX (Phenomenex, Torrance, California) cartridges to obtain high sensitivity (Chen et al. 2005). The extracts were applied to an online reversed phase SPE LC/MS system. The lower limit of detection was 2.5 fmol/mL when 10 mL of urine was used. 

Prior Applications. The first application of this traditional factor analysis method was an attempt by Blifford and Meeker (6) to interpret the elemental composition data obtained by the National Air Sampling Network(NASN) during 1957-61 in 30 U.S. cities. They employed a principal components analysis and Varimax rotation as well as a non-orthogonal rotation. In both cases, they were not able to extract much interpretable information from the data. Since there is a very wide variety of sources of particles in 30 cities and only 13 elements measured, it is not surprising that they were unable to provide much specificity to their factors. One interesting factor that they did identify was a copper factor. They were unable to provide a convincing interpretation. It is likely that this factor represents the copper contamination from the brushes of the high volume air samples that was subsequently found to be a common problem ( 2). 

Principal Components Analysis (PCA) is a multivariable statistical technique that can extract the strong correlations of a data set through a set of empirical orthogonal functions. Its historic origins may be traced back to the works of Beltrami in Italy (1873) and Jordan in Prance (1874) who independently formulated the singular value decomposition (SVD) of a square matrix. However, the first practical application of PCA may be attributed to Pearson s work in biology [226] following which it became a standard multivariate statistical technique [3, 121, 126, 128]. 

Matrix solid-phase dispersion (MSPD) is an SPE variant where samples are ground and mixed with a support. In the initial application, samples were placed in a disposable column previously packed with Florisil, which trapped the fat from the sample and allowed the compounds of interest to be eluted. This has successfully been applied to the determination of lipophilic pesticides from both fatty and non-fatty matrixes. Recently, an orthogonal technique, dispersive solid-phase extraction, for the isolation and analysis of a variety of pesticides on numerous food matrixes has been introduced. The technique is called QuEChERS, which stands for quick, easy, cheap, effective, rugged, and safe. The technique offers advantages in time and solvent usage since it uses approximately 10 ml of solvent per sample when compared to the potentially hundreds of milliliters of solvent used for more standard extraction and isolation protocols. It uses a combination of MgS04 and primary secondary amine (PSA) sorbent not only to remove water and non-target compounds, but also isolate the compounds of interest. 

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