method validation for non-routine methods
TRANSCRIPT
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Method validation for non-routine methods
Angelique Botha
Test and Measurement 2019 Conference
Misty Hills Conference Hotel
17 September 2019
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Overview
✓ Concept of method validation
✓ Method validation parameters
✓ Non-routine methods
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Concept of method validation
Method
Fit for purpose
Customer requirements
Specific laboratory
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Concept of method validation
Method validation
Overall method performance
Specific influence quantities
Normal use
Uncertainty of Measurement
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Concept of method validation
Method validation
data
Method development (optimisation)
Interlaboratory studies
In-house validation
Precision and bias
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Method validation parameters
✓ Principle of operation
✓ Precision
✓ Bias
✓ Linearity
✓ Limit of detection (LOD)
✓ Limit of quantification (LOQ)
✓ Working range
✓ Selectivity
✓ Robustness/Ruggedness
✓ Uncertainty of measurement
EURACHEM/CITAC Guide “Fitness for Purpose of Analytical Methods”,
Second edition, www.eurachem.org
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Precision study
Precision
Repeatability
Reproducibility
Intermediate precision
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Bias (“Trueness”) study
Bias
Certified reference materials (CRMs)
Spiking studies
Reference method
Eliminate
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Linearity
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Concentration mg/L
Cadmium in pineapples
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Limit of detection
blankblankLOD syy += 3
LODLOD xy →
y
xLOD say += 3
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Limit of quantification
For linear regression:
x
yLOQ say += 10
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Working range
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Concentration mg/L
Cadmium in pineapples
LOD
LOQ
Working range
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✓ Perform tests to determine the effect of one or more parameter changes on the results
✓ If the effect is significant a more detailed study is carried out to measure the size of the effect
✓ Significant effect: the precision deteriorated compared to the precision of the ruggedness test (ANOVA, F-test)
Robustness (ruggedness)
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✓ The degree to which a method responds uniquely to the required analyte
✓ Typical studies investigate the effects of likely interferents by adding the potential interferent to both blank and fortified samples and observing the response
✓ Normally used to demonstrate insignificant effects
✓ Can use the data to estimate the uncertainty associated with potential interferences
Selectivity/specificity
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Method validation for non-routine methods
Non-routine
methods
Standard method
Performance data
Bias
Duplicate analysis
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Standard method
Weigh 0,5 g aliquot of soil
sample
Add 8 mL HNO3, 5 mL
HCl, 3 mL HF
Leave overnight
First microwave
digestion step
Add 1 mL HF, 15 mL 5%
H3BO3
Second microwave
digestion step
Add internal standard
Matrix matchFill to the
mark
DiluteICP-MS analysis
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Standard method
Weigh 0,5 g aliquot of soil
sample
Add 8 mL HNO3, 5 mL
HCl, 3 mL HF
Leave overnight
First microwave
digestion step
Add 1 mL HF, 15 mL 5%
H3BO3
Second microwave
digestion step
Add internal standard
Matrix matchFill to the
mark
DiluteICP-MS analysis
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Standard method
Weigh 0,5 g aliquot of soil
sample
Add 8 mL HNO3, 5 mL
HCl, 3 mL HF
Leave overnight
First microwave
digestion step
Add 1 mL HF, 15 mL 5%
H3BO3
Second microwave
digestion step
Add internal standard
Matrix matchFill to the
mark
DiluteICP-MS analysis
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Standard method
Weigh 0,5 g aliquot of
rock sample
Add 8 mL HNO3, 5 mL
HCl, 3 mL HF
Leave overnight
First microwave
digestion step
Add 1 mL HF, 15 mL 5%
H3BO3
Second microwave
digestion step
Add internal standard
Matrix matchFill to the
mark
DiluteICP-MS analysis
![Page 20: Method validation for non-routine methods](https://reader030.vdocuments.net/reader030/viewer/2022012109/61dc7b95a826f16b383b9016/html5/thumbnails/20.jpg)
Standard method
Weigh 0,5 g aliquot of
rock sample
Add 10 mL HNO3, 6 mL
HCl, 5 mL HF
Leave overnight
First microwave
digestion step
Add 1 mL HF, 15 mL 5%
H3BO3
Second microwave
digestion step
Add internal standard
Matrix match Fill to the mark
DiluteICP-MS analysis
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