Orthogonal techniques

In addition Kondo and Yamashita (22), and others (15,17,18) have used Lowdin s work by applying the symmetrical orthogonalization technique to the chemical shifts in the alkali halides. All of these results agree remarkably well with the experimental data. 

To calculate the isomer shift (11) the electron density is obtained easily using the symmetric orthogonalization technique ... 

CE has been touted as a replacement for HPLC in the pharmaceutical industry. This was a shame, since the techniques are so different. For many measurements, it is an orthogonal technique to HPLC. Whereas HPLC separates based on interaction with the stationary phase, CE separates based on the ratio of charge to mass. There are numerous examples of where CE exceeds the resolving power of HPLC (e.g., ion analysis, chiral analysis, DNA quantification, separation, large molecule analysis, etc.). 

Even if HPLC is chosen as the main stability indicating method, CE will be useful as orthogonal technique, especially in cases where the reason of mass balance deviations is unclear. In addition, due to its increased peak capacity and selectivity in comparison to HPLC, the detection of possible enantiomers, stereoisomers, and position isomers, having the same molecular weight and equal/similar spectra as the drug substance may be separated by a secondary CE method. 

During the last decade capillary electrophoresis (CE) has become a mature separation technique for pharmaceutical analysis. Numerous validated methods from pharmaceutical R D lahoratories and academia have been reported in literature, including identity confirmation, main component assay, purity determination, enantiomeric separation, and stoichiometry determination. In addition, CE is frequently applied as an orthogonal technique during the development of stability indicating liquid chromatography methods. As a result CE... 

Accuracy Use of an orthogonal technique, spike recovery or inferred once specificity, linearity, and precision established... 

The accuracy of a method is defined as the closeness of the value obtained to known or accepted values. Accuracy can be determined in a number of ways, depending on the nature of the CZE method and availability of orthogonal techniques to compare results. If practical, spike recovery studies (i.e., testing to determine whether recovery matches the amount of a known analyte or impurity spiked) are good alternatives to orthogonal assay comparisons. ICH guidelines also allow method accuracy to be inferred, once specificity, linearity, and precision are established. 

III. CE AS AN ORTHOGONAL TECHNIQUE A. Selectivity Challenges in Applications of RPLC... 

Saavedra et ah used CE as orthogonal technique to HPLC to confirm the identification of a degradation product in alprazolam tablets during their stability assay. 

Caution needs to be exercised in confirmation of method specificity, as peak purity cannot be inferred from the absence of any mass spectrometric signals, as an absence could be because of ion suppression, or the response may too low to be detected, or the unknown may have different ionisation properties. Peak purity should be tested by using an orthogonal technique. 

The primary application for HIC has been in protein analysis and purification due to the good selectivity and preservation of biological activity [1-4]. Because of the major differences in selectivity, HIC can be used as an orthogonal technique to RPC, as well as to ion-exchange and size-exclusion chromatography. 

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