Validation of calibration models: Development and testing of a practical procedure Brigitte Desharnais, Félix Camirand-Lemyre, Pascal Mireault, Cameron D. Skinner
2014 Annual Meeting of the Society of Forensic Toxicologists Wednesday, October 22nd 2014
http://entre-deux-films.over-blog.com/article-un-peu-de-culture-le-cri-wilhelm-113761242.html (Consulted October 15th 2014)
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Choosing a Calibration Model Order Weighting
Linear
Quadratic
No weight 1/x 1/x2
“Ultimately, the best approach is to use the simplest calibration model that best fits the concentrationresponse relationship.” Cannot simply use r; Should be evaluated visually using standardized residual plots; Other alternatives: ANOVA LOF, significance of second order term, coefficient of determination. 3 Contact:
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Standardized Residuals Plot Tool
4 Contact:
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Standardized Residuals Plot Tool
Stepwise, systematic method Unbiased Choose model Validate model
5 Contact:
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Test Data LC-MS/MS method 50 analytes (benzodiazepines, amphetamines, opioids, cocaine and metabolites) 15 deuterated internal standards
Nine calibrants (5, 10, 15, 50, 75, 100, 400, 500, 1000 ng/mL) 5 replicates in the same run
6 Contact:
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Raw Data
7 Contact:
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Is Weighting Appropriate? Testing Heteroscedasticity with the F-Test Heteroscedastic
Homoscedastic
Error smaller at one concentration
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More confidence to those data points
WEIGHTING (More weight on those data points in regression calculation) 8
Is Weighting Needed? Testing Heteroscedasticity with the F-Test F-TEST
Comparison of Fcalc with the F Distribution Table. p>0.05 : Homoscedastic data No weighting p0.05 or negative Fcalc: linear)
p0.05: calibration model validated) 15 Contact:
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Food for thought The data used for this process should be: Intra-day or inter-day? Intra-batch (extraction) or inter-batch?
To consider: Production processes Mathematical theory Potential to yield an erroneous model Potential to validate an incorrect model (variability introduced)
16 Contact:
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Acknowledgements
Félix Camirand-Lemyre University of Sherbrooke
From the LSJML: Gabrielle Daigneault Marc-André Morel Julie Lacquerre Cynthia Côté Martine Lamarche Marie-Pierre Taillon Édith Viel Lucie Vaillancourt
Supervisors: Pascal Mireault Dr. Cameron Skinner From Concordia: Michel Boisvert John Chin
Funding:
17 Contact:
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