Method development strategy

E. A. Hogendoorn, C. Verscliraagen, U. A. Th Brinkman and van P. Zoonen Coupled column liquid chr omatography for the tr ace determination of polar pesticides in water using dhect large-volume injection method development strategy applied to methyl isothiocyanate , Awn/. Chim. Acm 268 205-215 (1992). 

Fillet, M., Hubert, P., Crommen, J. Method development strategies for the enantiosep-aration of drugs by capillary electrophoresis using cyclodextrins as chiral additives. Electrophoresis 1998, 19, 2834—2840. 

Chapman, J., Chen, F.A. Implementing a generic methods development strategy for enantiomer analysis. LC-GC Europe, 2001, January, 2-6. 

Methods development strategy for enantiomer analysis using the P/ACE MDQ chiral system, Application information A-1889A, Beckman coulter, www.beckman-coulter.com... 

Issue Industry and the regulatory authorities need to agree on (1) what constitutes a valid efficacy claim for each product type, (2) the test methods used to generate data in support of these claims and (3) a test method development strategy and plan for the most critical areas where methods are inadequate or missing. 

For these three materials, covalent bonding technologies cannot be used. With silanes, mixed anhydrides are formed lacking in hydrolytic stability. Coating with organic polymers [32] is the way to go. A bonded phase based on zirconia has been studied widely [43]. Method development strategies established with silica-based RP cannot be transferred to an RP bonded on zirconia. Selectivity is dependent, e.g., on the type of buffer used. Anions in the mobile phase influence retention. The kinetics of analyte interaction with the different active sites may lead to reduced efficiencies. 

When developing a separation, a strategy of mobile-phase selection is involved. However, when the molecule has a polar and a nonpolar part, the tactics that support the method development strategy differ slightly from the previous discussions. To illustrate the method development approach to be... 

The use of chaotropic counteranions for a chromatographic separation is beneficial as a method development strategy. These modiflers may replace the need for changing column type and/or addition of hydrophobic ion-pairing reagents for the more challenging separations. Further studies are needed to fully elucidate the detailed mechanism of chaotropic mobile-phase additives. 

Once a suitable HPLC separation mode has been selected, the experimental conditions should be adjusted to suit the objective of the separation. To proceed in this way, either empirical or systematic (statistical or predictive) HPLC method development strategies can be used. Any method development necessitates a convenient measure of the quality of separation. The separation of two sample compounds is most often measured either by resolution or by peak separation function (see Section 1.1.2). The resolution is an especially useful criterion of separation as its definition Eq. (1.3) can be transformed to another expression relating directly to the experimental conditions of separation v/A k... 

HPLC separation of polymers requires the removal of polymer prior to the analysis, low molecular weight SEC can operate without such need, as the polymer will Just be exeluded from the system. SEC presents a quick and easy method development strategy the process involves the selection of a suitable solvent and the use of any small pore size eolumns 50 A and 100 A. All eomponents will elute within a predetermined interval, amounting to one eolumn volume, and the elution volume of any material ean be predicted for a given eolumn provided a ealibration curve is available. 

Hewitt EF, Lukulay P, Galushko S (2006) Implementation of a rapid and automated high performance liquid chromatography method development strategy for pharmaceutical drug candidates. J Chromatogr A, 1107 79-87. 

Many method development strategies have been reported in the literature for different separation techniques [1,4,6]. Erom these, there appear to be common themes and generalised strategies that exist in aU the approaches reviewed to date - this will be discussed in the early sections of this chapter in sufficient detail to set the scene for the following sections. Part of this section will also look at why particular separation methods are used, and the in xtrtance of sample preparation will be discussed. A review of the hterature over the last five years has indicated that the most popular front-line separation techniques are HPLC, GC and CE. The next four sections will focus on each of the separation methods... 

In most pharmaceutical analyses, the answer to these questions is quite simple. The separation method will have to satisfy all the above criteria, because by meeting this criteria, the ruggedness of the method is tested. The end-user is most likely the QC laboratory in a manufacturing facility, and the ease with which a separation method can be transferred in most cases, R D laboratories to a QC laboratory will be highly dependent on the method development strategy used [37]. 

Sample preparation is an essential part of the separation process and is one of the key considerations at the start of any method development strategy. Numerous publications are available on this subject [38, 39]. In brief, the primary aim is to provide a reproducible and homogenous solution that is... 

Also, to further improve the book s content, I have asked M. Zoubair El Fallah to write the chapter on methods development. Zoubair s strong background in chromatographic theory as well as his broad practical experience made him the ideal choice for prefacing this chapter. Furthermore, we have previously cooperated in the elaboration of method development strategies, and some of the work reported in this chapter originated in this cooperation. 

We will now proceed to discuss method development strategies. First, we will contemplate the choice of isocratic or gradient methods. Then we will develop an efficient method development strategy. The focus of the method development is the analysis of low-molecular-weight ionizable compounds by reversed-phase HPLC. 

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