Quality Assurance and Method Selection

• Quality assurance ensures the right answer is obtained with sufficient accuracy and precision for informed decisions.
• There is no benefit to obtaining more accurate or precise answers than necessary.
• Data quality standards involve obtaining, correcting, and maintaining the right data.
• The aim is to ensure results meet customer needs, considering raw measurements, treated data, and statistically analyzed results, along with analytical procedure specifications.
• A false positive occurs when the concentration is below the legal limit but reported as exceeding it.
• A false negative occurs when the concentration is above the legal limit but reported as below it.

Method Selection Considerations

• Selectivity refers to the ability to distinguish the target analyte from other substances in a sample.
• Sensitivity refers to the ability to reliably detect and measure changes in analyte concentration.
• Blanks are samples that ideally do not contain the analyte and are used for quality control
• Method blanks contain all components except the analyte and undergo all procedure steps.
• Reagent blanks account for any trace amount of analyte present in the reagents used.
• Field blanks detect analyte contamination from field conditions.

Spike Recovery

• Response to an analyte can be affected (decreased, increased) by other substances in the sample.
• The matrix encompasses everything in an unknown sample except the analyte of interest.
• Spike recovery is assessed by adding a known quantity of an analyte to a sample.
• Spike recovery tests if the spike's response is as expected based on a known calibration curve.
• Discrepancies indicate contamination or loss issues.

Large Sample Set Management

• Regular calibration checks should be preformed
• Method drift can be due to changes in room temperature, degradation of reagents, or the degradation of standarads
• Calibration check solutions should be different from the ones used to prepare the original calibration curve
• Performance test samples help eliminate any bias from having an analyst know the concentrations of the calibration check samples
• Standard operating procedures outline the steps taken for a procedure and serve as control experiments to detect any problems in the lab

Assessment Protocols

• Assessment involves gathering data to confirm that analytical procedures are within specific limits.
• Assessment involves verifying that final results meet objectives.
• Control charts assist in monitoring performance and ensuring the method suits its intended use, guided by standard documentation.

Method Validation

• Method validation proves that an analytical method is acceptable for its specific purpose.
• Validation confirms method selectivity, linearity, accuracy, preciseness, range, detection, quantitation limits, and robustness.
• Selectivity is the extent to which a method can differentiate the analyte from everything else in the sample.
• An assay is specific if it selects for only one analyte.
• Linearity measures how well a calibration curve follows a straight line, indicating that the response is proportional to the quantity of the analyte
• Residual plots highlight differences between calibration data and least-square line.
• Accuracy is analyzing a certified reference, comparing the results, analyzing spiked blank sample, and standard additions of analyte.

Detection Limit (DL)

• The detection limit (LOD) is 3x the standard deviation of the blank
• The quantitation limit (LOQ) is 10x the standard deviation of the blank
• The reporting limit is the concentration below which regulations say analyte is reported as not detected
• Robustness is how well an analytical method can remain unaffected by small changes in operating parameters
• Range indicates the concentrations where linearity, accuracy, and precisions are tolerable

Standard Addition Technique

• The standard addition technique involves adding known quantities of the analyte to the unknown sample.
• An increase in signal indicates how much analyte was in the original unknown
• This method requires linear response to analyte concentration.
• Higher precision is achieved when standards are added by mass instead of volume.

Matrix Effects

• Matrix effects are changes in analytical sensitivity caused by other substances in the sample.
• Sample composition affects analytical signal
• It's difficult to create standards and blanks whose composition matches the sample, and therefore the standards and black don't match the composition of the unknown
• Makes traditional calibrations curves unreliable

Internal Standards

• Standard addition of a known amount of a compound is the same substance as an analyte that is added to the unknown
• External standards are solutions with known concentrations of analyte used to prepare the calibration curve
• Internal standards are known amounts of a compound that differs from the analyte added to the unknown
• Especially useful for analysis when quantity of sample analyzed or instrument response differs from run-to-run
• Desirable when sample loss can occur during sample preparation steps prior to analysis
• Helpful for internal standards to be chemically similar to analyte so that affect

One-Point Calibration (Internal Standard)

• Prepare a known mixture of standard and analyte
• Measure relative response of detector to the 2 species
• Detectors generally have different responses to each component

Multipoint Calibration Curve (Internal Standard)

• Multipoint calibration curve is preferred to average out experimental variability to verify linearity of response
• Construct graph of signal
• ratios concentration ratio
• Graph should be linear with zero intercept
• Slope of graph is response factor (F)