Defining the Scope and Method Requirements

The first technical considerations that the analyst must evaluate are the number of analytes that are to be detected and quantified, their structures and molecular masses, and the specific requirements for Umits of detection and quantitation, including the dynamic range of the assay (Section 8.4). Although these may seem to be obvious points at first glance, the answers to these questions will have a profound impact on the method design and feasibility. The next question has to do with the availabihty of standards and particularly whether or not a Certificate of Analysis (Sections 9.4.4c and 2.2.1) is available. In many instances the chent will be able to provide standards of known purity and stability, or they may be available through commercial sources, but in other cases it may be necessary to have reference substances synthesized. 

In any event, some type of documentation that estab-hshes the purity, source and lot number and expiration 

The importance of the surrogate internal standard (SIS) has been discussed throughout this book (Sections 2.2.3, 2.6.3 and 8.5.2b) and the type and availability of the SIS wiU have a profound impact on method design and rehabUity. In addition to what has been discussed previously, several practical considerations with respect to the SIS are covered in Section 9.4.5. 

Of course, none of the issues introduced above can be considered without knowledge of the analytical sample. As well as the nature and properties of the sample itself, the amount of sample available will affect the method design in terms of the required limit of quantification and the size of the sample aliquot that wiU be used. The practical considerations around the sample as it affects the method design are discussed in Section 9.4.6 along with requirements for sample receipt, storage and use. 

Related to the analytical sample is the control matrix that will be used for method development and for preparing QCs and matrix matched calibrators (Section 9.4.7). In addition, the amount of available control matrix will also impact the design of method development and validation studies, especially in instances where a suitable control is not available or in the case where a similar control matrix is very rare and/or extremely costly. 

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