A data-driven approach for the detection of internal standard outliers in targeted LC-MS/MS assays

Highlights • Identifying internal standard outliers in clinical mass spectrometry assays is imperative.• Current approaches for identifying outliers are arbitrary and do not account for assay drift.• A robust modelling strategy allows laboratories to define their own acceptance criteria from their own data.• This strategy is easily implemented and the code is freely available.

[1]  Manuel Koller,et al.  robustlmm : An R Package for Robust Estimation of Linear Mixed-Effects Models , 2016 .

[2]  C. Seger,et al.  Pitfalls associated with the use of liquid chromatography-tandem mass spectrometry in the clinical laboratory. , 2010, Clinical chemistry.

[3]  Sherry Wang,et al.  Does a stable isotopically labeled internal standard always correct analyte response? A matrix effect study on a LC/MS/MS method for the determination of carvedilol enantiomers in human plasma. , 2007, Journal of pharmaceutical and biomedical analysis.

[4]  DISCUSSION OF "ANALYSIS OF VARIANCE—WHY IT IS MORE IMPORTANT THAN EVER" BY A. GELMAN , 2005, math/0508528.

[5]  Michael H Buonarati,et al.  Investigations beyond standard operating procedure on internal standard response. , 2019, Bioanalysis.

[6]  A. Gelman.  Analysis of variance: Why it is more important than ever? , 2005, math/0504499.

[7]  Steve Weston,et al.  Foreach Parallel Adaptor for the 'parallel' Package , 2015 .

[8]  Hadley Wickham,et al.  ggplot2 - Elegant Graphics for Data Analysis (2nd Edition) , 2017 .

[9]  Hong Lai,et al.  Nonparametric bootstrapping for hierarchical data , 2010 .

[10]  Lionel Henry,et al.  A Grammar of Data Manipulation [R package dplyr version 1.0.2] , 2020 .

[11]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[12]  M. Knutsson,et al.  European Bioanalysis Forum: recommendation for dealing with internal standard variability. , 2014, Bioanalysis.

[13]  D. Bates,et al.  Fitting Linear Mixed-Effects Models Using lme4 , 2014, 1406.5823.

[14]  K. Meeran,et al.  Prednisolone Replacement Therapy Mimics the Circadian Rhythm More Closely Than Other Glucocorticoids. , 2016, The journal of applied laboratory medicine.

[15]  Steve Weston.  Provides Foreach Looping Construct [R package foreach version 1.5.0] , 2020 .

[16]  France Mentré,et al.  A comparison of bootstrap approaches for estimating uncertainty of parameters in linear mixed‐effects models , 2013, Pharmaceutical statistics.

[17]  Steve Weston,et al.  Provides Iterator Construct [R package iterators version 1.0.13] , 2020 .

[18]  Hadley Wickham,et al.  Reshaping Data with the reshape Package , 2007 .

[19]  H. Wickham.  Simple, Consistent Wrappers for Common String Operations , 2015 .