Use of Blanks During Method Development and Analysis

The different types of blanks that can be prepared and how they are used are discussed in this section. Although the focus of this chapter is on method development, it should be stated that blanks are also a fundamental component of method validation and sample analysis, and in fact are critical in terms of supporting the vahdity of the final analysis. 

As previously discussed (Section 9.4.7b), extracted control matrix is used to assess the selectivity for the method under development. The selectivity of the method is a function of the sample preparation (extraction and clean-up), chromatography and mass spectrometry conditions that are used for the method. Assuming that the control matrix is representative of the sample matrix to be analyzed, and that method blanks have been used to demonstrate that the method is free of exogenous interferences due to solvents, or to containers or other apparatus (a source of interferences that is often overlooked in the method development process), an extracted blank is used to demonstrate that the method has sufficient selectivity for the intended analytical purpose. When interferences at the expected retention time of the analyte being quantified are detected, modifications to the sample preparation and chromatography (and sometimes the ions monitored hy the method) can be made to improve the selectivity of the method. Recall (Section 9.4.7b) that only re-analysis of incurred samples can reveal interferences resulting from metahoUtes or degradates of the analyte with either or both of the analyte and SIS. 

Blanks are a vital component of the lahoratory quality control process. They are incorporated into all method development, vahdation and sample analysis schemes to monitor and mitigate laboratory contamination (Section 9.7.1). Also, with LC-MS calibration curves often covering up to three orders of magnitude, carryover due to insufficient rinsing of the syringe needle or autoinjector is common and blanks (extracted blanks in particular) are used to assess and quantify the impact of the carryover on the final method (Section 9.7.2). 

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