References:

[1] B. Desharnais, F. Camirand-Lemyre, P. Mireault, C. D. Skinner, Procedure for the selection and validation of a calibration model I — Description and application, Journal of Analytical Toxicology 41 (4) (2017) 261–268. doi:10.1093/jat/bkx001.

[2] B. Desharnais, F. Camirand-Lemyre, P. Mireault, C. D. Skinner, Procedure for the selection and validation of a calibration model II — Theoretical basis, Journal of Analytical Toxicology 41 (4) (2017) 269–276. doi:10.1093/jat/bkx002.

[3] B. Desharnais, M.-J. Lajoie, J. Laquerre, S. Savard, P. Mireault, C. D. Skinner, A tool for automatic correction of endogenous concentrations: application to BHB analysis by LC–MS-MS and GC-MS, Journal of Analytical Toxicology 43 (7) (2019) 512–519. doi:10.1093/jat/bkz024.

[4] F. Camirand Lemyre, B. Desharnais, J. Laquerre, M.-A. Morel, C. Côté, P. Mireault, C. D. Skinner, Qualitative method validation and uncertainty evaluation via the binary output I — Validation guidelines and theoretical foundations, Journal of Analytical Toxicology (2019) submission number JAT–19–2881.

[5] B. Desharnais, M.-J. Lajoie, J. Laquerre, P. Mireault, C. D. Skinner, Qualitative method validation and uncertainty estimation via the binary output II — Application to a multi-analyte LC-MS/MS method for oral fluid, Journal of Analytical Toxicology (2019) submission number JAT–19–2882.


[6] B. Desharnais, P. Mireault, C. D. Skinner, Postmortem estimation of metabolic capacity through cytochrome P450 enzyme characterisation and quantification — A proof of concept.

[7] A. Moffat, M. Osselton, B. Widdop, S. Jickells, A. Negrusz, Introduction to forensic toxicology, in: A. Negrusz, G. Cooper (Eds.), Clarke’s Analytical Forensic Toxicology, 2nd Edition, Pharmaceutical Press, London, United Kingdom, 2013, Ch. 1, pp. 1–10.

[8] B. A. Goldberger, D. Lee, D. G. Wilkins, Analytical and forensic toxicology, in: C. D. Klaassen (Ed.), Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition, McGraw-Hill Education / Medical, New York, United States, 2018, Ch. 32, pp. 1511–1529.

[9] H. Druid, P. Holmgren, B. Carlsson, J. Ahlner, Cytochrome P450 2D6 (CYP2D6) genotyping on postmortem blood as a supplementary tool for interpretation of forensic toxicological results, Forensic Science International 99 (1) (1999) 25–34. doi:10.1016/S0379-0738(98)00169-8.

[10] S. H. Wong, M. A. Wagner, J. M. Jentzen, C. Schur, J. Bjerke, S. B. Gock, C.-C. Chang, Pharmacogenomics as an aspect of molecular autopsy for forensic pathology/toxicology: does genotyping CYP 2D6 serve as an adjunct for certifying methadone toxicity?, Journal of Forensic Sciences 48 (6) (2003) 1406–1415. doi:10.1520/JFS2002392.

[11] A. Sajantila, J. Palo, I. Ojanperä, C. Davis, B. Budowle, Pharmacogenetics in medicolegal context, Forensic Science International 203 (1-3) (2010) 44–52. doi:10.1016/j.forsciint.2010.09.011.

[12] P. Wexler, A. N. Hayes, The evolving journey of toxicology: A historical glimpse, in: C. D. Klaassen (Ed.), Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition, McGraw-Hill Education / Medical, New York, United States, 2018, Ch. 1, pp. 3–23.

[13] A. Parkinson, B. W. Ogilvie, D. B. Buckley, F. Kazmi, O. Parkinson, Biotransformation of xenobiotics, in: C. D. Klaassen (Ed.), Casarett & Doull’s Toxicology: The Basic Science of Poisons, 9th Edition, McGraw-Hill Education / Medical, New York, United States, 2018, Ch. 6, pp. 193–399.

[14] U. M. Zanger, M. Schwab, Cytochrome P450 enzymes in drug metabolism: regulation of gene expression, enzyme activities, and impact of genetic variation, Pharmacology & Therapeutics 138 (1) (2013) 103–141. doi:10.1016/j.pharmthera.2012.12.007.

[15] A. DePriest, B. Puet, A. Holt, A. Roberts, E. Cone, Metabolism and disposition of prescription opioids: a review, Forensic Science Review 27 (2) (2015) 115–145.

[16] M. Ingelman-Sundberg, Human drug metabolising cytochrome P450 enzymes: properties and polymorphisms, Naunyn-Schmiedeberg’s Archives of Pharmacology 369 (1) (2004) 89–104. doi:10.1007/s00210-003-0819-z.

[17] P. Holmgren, J. Ahlner, Pharmacogenomics for forensic toxicology: Swedish experience, in: S. H. Y. Wong, M. W. Linder, R. Valdes Jr. (Eds.), Pharmacogenomics Proteomics Enabling the Practice of Personalized Medicine, AACC Press, Washington, United States, 2006, Ch. 28, pp. 295–299.

[18] A. Gaedigk, M. Ingelman-Sundberg, N. A. Miller, J. S. Leeder, M. Whirl-Carrillo, T. E. Klein, P. S. Committee, The Pharmacogene Variation (PharmVar) Consortium: incorporation of the human cytochrome P450 (CYP) allele nomenclature database, Clinical Pharmacology & Therapeutics 103 (3) (2018) 399–401. doi:10.1002/cpt.910.

[19] C. M. Hunt, W. R. Westerkam, G. M. Stave, Effect of age and gender on the activity of human hepatic CYP3A, Biochemical Pharmacology 44 (2) (1992) 275–283. doi: 10.1016/0006-2952(92)90010-G.

[20] Z. E. Barter, J. E. Chowdry, J. R. Harlow, J. E. Snawder, J. C. Lipscomb, A. Rostami-Hodjegan, Covariation of human microsomal protein per gram of liver with age: absence of influence of operator and sample storage may justify interlaboratory data pooling, Drug Metabolism and Disposition 36 (12) (2008) 2405–2409. doi:10.1124/dmd.108.021311.

[21] R. Wolbold, K. Klein, O. Burk, A. K. Nüssler, P. Neuhaus, M. Eichelbaum, M. Schwab, U. M. Zanger, Sex is a major determinant of CYP3A4 expression in human liver, Hepatology 38 (4) (2003) 978–988. doi:10.1002/hep.1840380424.

[22] Y. Shao, X. Yin, D. Kang, B. Shen, Z. Zhu, X. Li, H. Li, L. Xie, G. Wang, Y. Liang, An integrated strategy for the quantitative analysis of endogenous proteins: A case of gender-dependent expression of P450 enzymes in rat liver microsome, Talanta 170 (2017) 514–522. doi:10.1016/j.talanta.2017.04.050.

[23] B. Madea, P. Saukko, A. Oliva, F. Musshoff, Molecular pathology in forensic medicine – introduction, Forensic Science International 203 (1-3) (2010) 3–14. doi:10.1016/j.forsciint.2010.07.017.

[24] M. Bosilkovska, C. Samer, J. Déglon, A. Thomas, B. Walder, J. Desmeules, Y. Daali, Evaluation of mutual drug–drug interaction within Geneva Cocktail for cytochrome P450 phenotyping using innovative dried blood sampling method, Basic & clinical pharmacology & toxicology 119 (3) (2016) 284–290. doi:10.1111/bcpt.12586.

[25] D. W. Nebert, Role of genetics and drug metabolism in human cancer risk, Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 247 (2) (1991) 267–281. doi:10.1016/0027-5107(91)90022-G.

[26] N. Djordjevic, D. D. Milovanovic, M. Radovanovic, I. Radosavljevic, S. Obradovic, M. Jakovljevic, D. Milovanovic, J. R. Milovanovic, S. Jankovic, CYP1A2 genotype affects carbamazepine pharmacokinetics in children with epilepsy, European Journal of Clinical Pharmacology 72 (4) (2016) 439–445. doi:10.1007/s00228-015-2006-9.

[27] M. Nakajima, R. Yoshida, T. Fukami, H. L. McLeod, T. Yokoi, Novel human CYP2A6 alleles confound gene deletion analysis, FEBS Letters 569 (1-3) (2004) 75–81. doi: 10.1016/j.febslet.2004.05.053.

[28] C.-C. Chang, P.-C. Lin, C.-H. Lin, K.-T. Yeh, H.-Y. Hung, J.-G. Chang, Rapid identification of CYP2C8 polymorphisms by high resolution melting analysis, Clinica Chimica Acta 413 (1-2) (2012) 298–302. doi:10.1016/j.cca.2011.10.005.

[29] B. D. Swar, S. R. Bendkhale, A. Rupawala, K. Sridharan, N. J. Gogtay, U. M. Thatte, N. A. Kshirsagar, Evaluation of cytochrome P450 2C9 activity in normal, healthy, adult Western Indian population by both phenotyping and genotyping, Indian Journal of Pharmacology 48 (3) (2016) 248. doi:10.3109/09537104.2015.1095875.

[30] J. H. Lee, S. G. Ahn, J.-W. Lee, Y. J. Youn, M.-S. Ahn, J.-Y. Kim, B.-S. Yoo, S.-H. Lee, J. Yoon, J. Kim, et al., Switching from prasugrel to clopidogrel based on Cytochrome P450 2C19 genotyping in East Asian patients stabilized after acute myocardial infarction, Platelets 27 (4) (2016) 301–307. doi:10.3109/09537104.2015.1095875.

[31] S. Ben, R. M. Cooper-DeHoff, H. K. Flaten, O. Evero, T. M. Ferrara, R. A. Spritz, A. A. Monte, Multiplex SNaPshot—a new simple and efficient CYP2D6 and ADRB1 genotyping method, Human Genomics 10 (1) (2016) 11. doi:10.1186/s40246-016-0073-3.

[32] C. Innocenti, A. Accorsi, V. Cerreta, V. Mantovani, F. Violante, Fast CYP2E1 genotyping using automated fluorescent detection, La Medicina del Lavoro 97 (6) (2006) 799–804.

[33] M. Jin, S. B. Gock, P. J. Jannetto, J. M. Jentzen, S. H. Wong, Pharmacogenomics as molecular autopsy for forensic toxicology: genotyping cytochrome P450 3A4* 1B and 3A5* 3 for 25 fentanyl cases, Journal of Analytical Toxicology 29 (7) (2005) 590–598. doi:10.1093/jat/29.7.590.

[34] J. Frost, A. Helland, I. S. Nordrum, L. Slørdal, Investigation of morphine and morphine glucuronide levels and cytochrome P450 isoenzyme 2D6 genotype in codeine related deaths, Forensic Science International 220 (1-3) (2012) 6–11. doi:10.1016/j.forsciint.2012.01.019.

[35] Y. He, J. Brockmöller, H. Schmidt, I. Roots, J. Kirchheiner, CYP2D6 ultrarapid metabolism and morphine/codeine ratios in blood: was it codeine or heroin?, Journal of Analytical Toxicology 32 (2) (2008) 178–182. doi:10.1093/jat/32.2.178.

[36] M. Kingbäck, L. Karlsson, A.-L. Zackrisson, B. Carlsson, M. Josefsson, F. Bengtsson, J. Ahlner, F. C. Kugelberg, Influence of CYP2D6 genotype on the disposition of the enantiomers of venlafaxine and its major metabolites in postmortem femoral blood, Forensic Science International 214 (1-3) (2012) 124–134. doi:10.1016/j.forsciint.2011.07.034.

[37] A. Levo, A. Koski, I. Ojanperä, E. Vuori, A. Sajantila, Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood, Forensic Science International 135 (1) (2003) 9–15. doi:10.1016/S0379-0738(03)00159-2.

[38] P. Holmgren, B. Carlsson, A.-L. Zackrisson, B. Lindblom, M.-L. Dahl, M. G. Scordo, H. Druid, J. Ahlner, Enantioselective analysis of citalopram and its metabolites in postmortem blood and genotyping for CYD2D6 and CYP2C19, Journal of Analytical Toxicology 28 (2) (2004) 94–104. doi:10.1093/jat/28.2.94.

[39] P. J. Jannetto, S. H. Wong, S. B. Gock, E. Laleli-Sahin, B. C. Schur, J. M. Jentzen, Pharmacogenomics as molecular autopsy for postmortem forensic toxicology: genotyping cytochrome P450 2D6 for oxycodone cases, Journal of Analytical Toxicology 26 (7) (2002) 438–447. doi:10.1093/jat/26.7.438.

[40] G. Koren, J. Cairns, D. Chitayat, A. Gaedigk, S. J. Leeder, Pharmacogenetics of morphine poisoning in a breastfed neonate of a codeine-prescribed mother, The Lancet 368 (2006) 704. doi:10.1016/S0140-6736(06)69255-6.

[41] F. R. Sallee, C. L. DeVane, R. E. Ferrell, Fluoxetine-related death in a child with cytochrome P-450 2D6 genetic deficiency, Journal of Child and Adolescent Psychopharmacology 10 (1) (2000) 27–34. doi:10.1089/cap.2000.10.27.

[42] A. Koski, I. Ojanperä, J. Sistonen, E. Vuori, A. Sajantila, A fatal doxepin poisoning associated with a defective CYP2D6 genotype, The American Journal of Forensic Medicine and Pathology 28 (3) (2007) 259–261. doi:10.1097/PAF.0b013e3180326701.

[43] R. D. Dowell, O. Ryan, A. Jansen, D. Cheung, S. Agarwala, T. Danford, D. A. Bernstein, P. A. Rolfe, L. E. Heisler, B. Chin, et al., Genotype to phenotype: a complex problem, Science 328 (5977) (2010) 469. doi:10.1126/science.1189015.

[44] C. Seibert, B. R. Davidson, B. J. Fuller, L. H. Patterson, W. J. Griffiths, Y. Wang, Multiple-approaches to the identification and quantification of cytochromes P450 in human liver tissue by mass spectrometry, Journal of Proteome Research 8 (4) (2008) 1672–1681. doi:10.1021/pr800795r.

[45] W. Crochot, Diagram of the Cell Membrane’s Structures and Their Funtion, Figure (2014). URL https://en.wikipedia.org/wiki/Cell_membrane#/media/File:Cell_membrane_drawing-en.svg

[46] P. Picotti, R. Aebersold, Selected reaction monitoring–based proteomics: workflows, potential, pitfalls and future directions, Nature Methods 9 (6) (2012) 555.

[47] M. Z. Wang, J. Q. Wu, J. B. Dennison, A. S. Bridges, S. D. Hall, S. Kornbluth, R. R. Tidwell, P. C. Smith, R. D. Voyksner, M. F. Paine, et al., A gel-free MSbased quantitative proteomic approach accurately measures cytochrome P450 protein concentrations in human liver microsomes, Proteomics 8 (20) (2008) 4186–4196. doi: 10.1002/pmic.200800144.

[48] B. Rathgeber, J. Boles, P. Shand, Rapid postmortem pH decline and delayed chilling reduce quality of turkey breast meat, Poultry Science 78 (3) (1999) 477–484. doi: 10.1093/ps/78.3.477.

[49] Traditional Methods of Cell Lysis, Handbook, ThermoFisher Scientific (2019). URL https://www.thermofisher.com/ca/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/traditional-methods-cell-lysis.html

[50] Protein Preparation Handbook, Handbook, ThermoFisher Scientific (2016). URL https://assets.thermofisher.com/TFS-Assets/BID/Handbooks/protein-preparation-handbook.pdf

[51] M. K. Rasmussen, B. Ekstrand, G. Zamaratskaia, Comparison of cytochrome P450 concentrations and metabolic activities in porcine hepatic microsomes prepared with two different methods, Toxicology In Vitro 25 (1) (2011) 343–346. doi:10.1016/j.tiv.2010.10.007.

[52] Y. Nakatani, V. Ogryzko, Immunoaffinity purification of mammalian protein complexes, Methods in Enzymology 370 (2003) 430–444. doi:10.1016/S0076-6879(03)70037-8.

[53] Y. Hatefi, W. Hanstein, Solubilization of particulate proteins and nonelectrolytes by chaotropic agents, Proceedings of the National Academy of Sciences 62 (4) (1969) 1129–1136. doi:10.1073/pnas.62.4.1129.

[54] F. Lottspeich, Top down and bottom up analysis of proteins (focusing on quantitative aspects), in: T. Letzel (Ed.), Protein and Peptide Analysis by LC-MS: Experimental Strategies, Royal Society of Chemistry, London, United Kingdom, 2011, Ch. 1, pp.1–10. doi:10.1039/9781849733144-00001.

[55] J. Barbour, S. Wiese, H. E. Meyer, B. Warscheid, Mass spectrometry, in: J. von Hagen (Ed.), Proteomics Sample Preparation, Wiley, Hoboken, United States, 2008, Ch. 4, pp. 41–128. doi:10.1002/9783527622832.ch4.

[56] E. Gasteiger, A. Gattiker, C. Hoogland, I. Ivanyi, R. D. Appel, A. Bairoch, ExPASy: the proteomics server for in-depth protein knowledge and analysis, Nucleic Acids Research 31 (13) (2003) 3784–3788. doi:10.1093/nar/gkg563.

[57] D. A. Skoog, F. J. Holler, S. R. Crouch, Liquid chromatography, in: Principles of Instrumental Analysis, 6th Edition, Thomson Higher Education, Belmont, United States, 2006, Ch. 28, pp. 816–855.

[58] J. B. Fenn, M. Mann, C. K. Meng, S. F. Wong, C. M. Whitehouse, Electrospray ionization–principles and practice, Mass Spectrometry Reviews 9 (1) (1990) 37–70. doi:10.1002/mas.1280090103.

[59] V. Lange, P. Picotti, B. Domon, R. Aebersold, Selected reaction monitoring for quantitative proteomics: a tutorial, Molecular Systems Biology 4 (1) (2008) 222. doi:10.1038/msb.2008.61.

[60] A. A. Dowle, J. Wilson, J. R. Thomas, Comparing the diagnostic classification accuracy of iTRAQ, peak-area, spectral-counting, and emPAI methods for relative quantification in expression proteomics, Journal of Proteome Research 15 (10) (2016) 3550–3562. doi:10.1021/acs.jproteome.6b00308.

[61] C. Lindemann, N. Thomanek, F. Hundt, T. Lerari, H. E. Meyer, D. Wolters, K. Marcus, Strategies in relative and absolute quantitative mass spectrometry based proteomics, Biological Chemistry 398 (5-6) (2017) 687–699. doi:10.1515/hsz-2017-0104.

[62] C. Ludwig, R. Aebersoldab, Getting Absolute: Determining Absolute Protein Quantities via Selected Reaction Monitoring Mass Spectrometry, in: C. E. Eyers, S. Gaskell (Eds.), Quantitative Proteomics, Royal Society of Chemistry, London, United Kingdom, 2014, Ch. 4, pp. 80–109. doi:10.1039/9781782626985-00080.

[63] S. A. Gerber, J. Rush, O. Stemman, M. W. Kirschner, S. P. Gygi, Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS, Proceedings of the National Academy of Sciences 100 (12) (2003) 6940–6945. doi: 10.1073/pnas.0832254100.

[64] C. M. Shuford, J. J. Walters, P. M. Holland, U. Sreenivasan, N. Askari, K. Ray, R. P. Grant, Absolute protein quantification by mass spectrometry: not as simple as advertised, Analytical Chemistry 89 (14) (2017) 7406–7415. doi:10.1021/acs.analchem.7b00858.

[65] H. Kawakami, S. Ohtsuki, J. Kamiie, T. Suzuki, T. Abe, T. Terasaki, Simultaneous absolute quantification of 11 cytochrome P450 isoforms in human liver microsomes by liquid chromatography tandem mass spectrometry with in silico target peptide selection, Journal of Pharmaceutical Sciences 100 (1) (2011) 341–352. doi:10.1002/jps.22255.

[66] C. Lane, S. Nisar, W. Griffiths, B. Fuller, B. Davidson, J. Hewes, K. Welham, L. Patterson, Identification of cytochrome P450 enzymes in human colorectal metastases and the surrounding liver: a proteomic approach, European Journal of Cancer 40 (14) (2004) 2127–2134. doi:10.1016/j.ejca.2004.04.029.

[67] E. Langenfeld, U. M. Zanger, K. Jung, H. E. Meyer, K. Marcus, Mass spectrometry based absolute quantification of microsomal cytochrome P450 2D6 in human liver, Proteomics 9 (9) (2009) 2313–2323. doi:10.1002/pmic.200800680.

[68] R. E. Jenkins, N. R. Kitteringham, C. L. Hunter, S. Webb, T. J. Hunt, R. Elsby, R. B. Watson, D. Williams, S. R. Penningtonand, B. K. Park, Relative and absolute quantitative expression profiling of cytochromes P450 using isotope-coded affinity tags, Proteomics 6 (6) (2006) 1934–1947. doi:10.1002/pmic.200500432.

[69] C. S. Lane, Y. Wang, R. Betts, W. J. Griffiths, L. H. Patterson, Comparative cytochrome P450 proteomics in the livers of immunodeficient mice using 18O stable isotope labeling, Molecular & Cellular Proteomics 6 (6) (2007) 953–962. doi: 10.1074/mcp.M600296-MCP200.

[70] B. Achour, J. Barber, A. Rostami-Hodjegan, Cytochrome P450 pig liver pie: determination of individual cytochrome P450 isoform contents in microsomes from two pig livers using liquid chromatography in conjunction with mass spectrometry, Drug Metabolism and Disposition 39 (11) (2011) 2130–2134. doi:10.1124/dmd.111.040618.

[71] General requirements for the competence of testing and calibration laboratories, Standard ISO/IEC 17025:2005, International Organization for Standardization, Geneva, Switzerland (2005). URL https://www.iso.org/standard/39883.html

[72] General requirements for the competence of testing and calibration laboratories, Standard ISO/IEC 17025:2017, International Organization for Standardization, Geneva, Switzerland (2017). URL https://www.iso.org/standard/66912.html

[73] Guidelines for the Accreditation of Forensic Testing Laboratories, Standard CAN-P-1578, Standards Council of Canada (Conseil canadien des normes), Ottawa, Canada (2009). URL https://www.scc.ca/en/about-scc/publications/scc-requirements-and-guidance-for-accreditation-for-forensic-testing-laboratories

[74] D. A. Skoog, F. J. Holler, S. R. Crouch, Introduction, in: Principles of Instrumental Analysis, 6th Edition, Thomson Higher Education, Belmont, United States, 2006, Ch. 1, pp. 1–24.

[75] Scientific Working Group for Forensic Toxicology, Scientific Working Group for Forensic Toxicology (SWGTOX) standard practices for method validation in forensic toxicology, Journal of Analytical Toxicology 37 (7) (2013) 452–474. doi:10.1093/jat/bkt054.

[76] Gold Book - Limit of Detection, Standard, International Union of Pure and Applied Chemistry, Research Triangle Park, United States (2014). URL https://goldbook.iupac.org/terms/view/L03540

[77] M. Haenlein, A. M. Kaplan, A beginner’s guide to partial least squares analysis, Understanding Statistics 3 (4) (2004) 283–297. doi:10.1207/s15328031us0304\_4.

[78] G. R. Jones, Postmortem toxicology, in: A. Negrusz, G. Cooper (Eds.), Clarke’s Analytical Forensic Toxicology, 2nd Edition, Pharmaceutical Press, London, United Kingdom, 2013, Ch. 7, pp. 189–214.

[79] Bioanalytical Method Validation – Guidance for Industry, Standard, Food and Drug Administration, Silver Springs, United States (May 2018). URL http://www.fda.gov/downloads/Drugs/Guidances/ucm070107.pdf

[80] Guideline on Bioanalytical Method Validation, Standard, European Medicines Agency, London, United Kingdom (2011). URL https://www.ema.europa.eu/documents/scientific-guideline/guideline-bioanalytical-method-validation_en.pdf

[81] Standard Practices for Method Validation in Forensic Toxicology (Draft), Standard, American Academy of Forensic Sciences Standards Board, Colorado Springs, United States (2018). URL https://asb.aafs.org/wp-content/uploads/2018/09/036_Std_Ballot02.pdf

[82] E. Stokvis, H. Rosing, J. H. Beijnen, Stable isotopically labeled internal standards in quantitative bioanalysis using liquid chromatography/mass spectrometry: necessity or not?, Rapid Communications in Mass Spectrometry 19 (3) (2005) 401–407. doi: 10.1002/rcm.1790.

[83] M. S. Halquist, H. T. Karnes, Quantification of Alefacept, an immunosuppressive fusion protein in human plasma using a protein analogue internal standard, trypsin cleaved signature peptides and liquid chromatography tandem mass spectrometry, Journal of Chromatography B 879 (11–12) (2011) 789–798. doi:10.1016/j.jchromb.2011.02.034.

[84] J. D. Ingle, S. R. Crouch, Signal-to-noise ratio considerations, in: Spectrochemical Analysis, Prentice Hall, Englewood Cliffs, United States, 1988, Ch. 5, pp. 135–163.

[85] D. Massart, B. Vandeginste, L. Buydens, S. De Jong, P. Lewi, J. Smeyers-Verbeke, Straight line regression and calibration, in: Handbook of Chemometrics and Qualimetrics: Part A, Vol. 20A of Data Handling in Science and Technology, Elsevier, Amsterdam, Netherlands, 1997, Ch. 8, pp. 171–230.

[86] D. Massart, B. Vandeginste, L. Buydens, S. De Jong, P. Lewi, J. Smeyers-Verbeke, Multiple and polynomial regression, in: Handbook of Chemometrics and Qualimetrics: Part A, Vol. 20A of Data Handling in Science and Technology, Elsevier, Amsterdam, Netherlands, 1997, Ch. 10, pp. 263–303.

[87] K. Tang, J. S. Page, R. D. Smith, Charge competition and the linear dynamic range of detection in electrospray ionization mass spectrometry, Journal of the American Society for Mass Spectrometry 15 (10) (2004) 1416–1423. doi:10.1016/j.jasms.2004.04.034.

[88] H. Gu, G. Liu, J. Wang, A.-F. Aubry, M. E. Arnold, Selecting the correct weighting factors for linear and quadratic calibration curves with least-squares regression algorithm in bioanalytical LC-MS/MS assays and impacts of using incorrect weighting factors on curve stability, data quality, and assay performance, Analytical Chemistry 86 (18) (2014) 8959–8966. doi:10.1021/ac5018265.

[89] M. A. Babyak, What you see may not be what you get: a brief, nontechnical introduction to overfitting in regression-type models, Psychosomatic Medicine 66 (3) (2004) 411–421.

[90] F. P Busardo, A. W Jones, GHB pharmacology and toxicology: acute intoxication, concentrations in blood and urine in forensic cases and treatment of the withdrawal syndrome, Current Neuropharmacology 13 (1) (2015) 47–70.

[91] S. M. Darby, M. L. Miller, R. O. Allen, M. LeBeau, A mass spectrometric method for quantitation of intact insulin in blood samples, Journal of Analytical Toxicology 25 (1) (2001) 8–14. doi:10.1093/jat/25.1.8.

[92] Y. Lood, A. Eklund, M. Garle, J. Ahlner, Anabolic androgenic steroids in police cases in Sweden 1999–2009, Forensic Science International 219 (1–3) (2012) 199–204. doi: 10.1016/j.forsciint.2012.01.004.

[93] C. Hess, K. Sydow, T. Kueting, M. Kraemer, A. Maas, Considerations regarding the validation of chromatographic mass spectrometric methods for the quantification of endogenous substances in forensics, Forensic Science International 283 (2018) 150–155. doi:10.1016/j.forsciint.2017.12.019.

[94] S. M. Wille, F. T. Peters, V. Di Fazio, N. Samyn, Practical aspects concerning validation and quality control for forensic and clinical bioanalytical quantitative methods, Accreditation and Quality Assurance 16 (6) (2011) 279. doi:10.1007/s00769-011-0775-0.

[95] S. P. Elliott, Gamma hydroxybutyric acid (GHB) concentrations in humans and factors affecting endogenous production, Forensic Science International 133 (1-2) (2003) 9–16. doi:10.1016/S0379-0738(03)00043-4.

[96] M. Jemal, A. Schuster, D. B. Whigan, Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine: method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard, Rapid Communications in Mass Spectrometry 17 (15) (2003) 1723–1734. doi:10.1002/rcm.1112.

[97] D. Ji, C.-G. Jang, S. Lee, A sensitive and accurate quantitative method to determine N-arachidonoyldopamine and N-oleoyldopamine in the mouse striatum using column switching LC–MS–MS: use of a surrogate matrix to quantify endogenous compounds, Analytical and Bioanalytical Chemistry 406 (18) (2014) 4491–4499. doi:10.1007/s00216-014-7816-6.

[98] B. R. Jones, G. A. Schultz, J. A. Eckstein, B. L. Ackermann, Surrogate matrix and surrogate analyte approaches for definitive quantitation of endogenous biomolecules, Bioanalysis 4 (19) (2012) 2343–2356. doi:10.4155/bio.12.200.

[99] T. M. Binz, U. Braun, M. R. Baumgartner, T. Kraemer, Development of an LC–MS/MS method for the determination of endogenous cortisol in hair using 13C3-labeled cortisol as surrogate analyte, Journal of Chromatography B 1033 (2016) 65–72. doi: 10.1016/j.jchromb.2016.07.041.

[100] S. Kang, S. M. Oh, K. H. Chung, S. Lee, A surrogate analyte-based LC–MS/MS method for the determination of -hydroxybutyrate (GHB) in human urine and variation of endogenous urinary concentrations of GHB, Journal of Pharmaceutical and Biomedical Analysis 98 (2014) 193–200. doi:10.1016/j.jpba.2014.05.028.

[101] D. A. Skoog, F. J. Holler, S. R. Crouch, Selecting an analytical method, in: Principles of Instrumental Analysis, 6th Edition, Thomson Higher Education, Belmont, United States, 2006, Ch. 1E, pp. 17–21.

[102] D. Hughes, The world anti-doping code in sport: update for 2015, Australian Prescriber 38 (5) (2015) 167–170. doi:10.18773/austprescr.2015.059.

[103] F. P. Carvalho, Pesticides, environment, and food safety, Food and Energy Security 6 (2) (2017) 48–60. doi:10.1002/fes3.108.

[104] An Act to amend the Criminal Code (offences relating to conveyances) and to make consequential amendments to other Acts, Legislation S.C. 2018, c. 21, Bill C-46, Government of Canada, Ottawa, Canada (2018). URL http://www.parl.ca/DocumentViewer/en/42-1/bill/C-46/royal-assent

[105] C. de Souza Gondim, O. A. M. Coelho, R. L. Alvarenga, R. G. Junqueira, S. V. C. de Souza, An appropriate and systematized procedure for validating qualitative methods: Its application in the detection of sulfonamide residues in raw milk, Analytica Chimica Acta 830 (2014) 11–22. doi:10.1016/j.aca.2014.04.050.

[106] M. I. López, M. P. Callao, I. Ruisánchez, A tutorial on the validation of qualitative methods: From the univariate to the multivariate approach, Analytica Chimica Acta 891 (2015) 62–72. doi:10.1016/j.aca.2015.06.032.

[107] E. Trullols, I. Ruisánchez, F. Rius, J. Huguet, Validation of qualitative methods of analysis that use control samples, Trends in Analytical Chemistry 24 (6) (2005) 516–524. doi:10.1016/j.trac.2005.04.001.

[108] V. Vindenes, B. Yttredal, E. Øiestad, H. Waal, J. Bernard, J. Mørland, A. Christophersen, Oral fluid is a viable alternative for monitoring drug abuse: detection of drugs in oral fluid by liquid chromatography-tandem mass spectrometry and comparison to the results from urine samples from patients treated with methadone or buprenorphine, Journal of Analytical Toxicology 35 (1) (2011) 32–39. doi:10.1093/anatox/35.1.32.

[109] S. M. Wille, V. Di Fazio, S. W. Toennes, J. H. van Wel, J. G. Ramaekers, N. Samyn, Evaluation of Δ9-tetrahydrocannabinol detection using DrugWipe5S® screening and oral fluid quantification after Quantisal™ collection for roadside drug detection via a controlled study with chronic cannabis users, Drug Testing and Analysis 7 (3) (2015) 178–186. doi:10.1002/dta.1660.

[110] L. D. Edwards, K. L. Smith, T. Savage, Drugged driving in Wisconsin: oral fluid versus blood, Journal of Analytical Toxicology 41 (6) (2017) 523–529. doi:10.1093/jat/bkx051.

[111] S. Strano-Rossi, E. Castrignanò, L. Anzillotti, G. Serpelloni, R. Mollica, F. Tagliaro, J. P. Pascali, D. Di Stefano, R. Sgalla, M. Chiarotti, Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC–MS/MS analysis, Forensic Science International 221 (1-3) (2012) 70–76. doi:10.1016/j.forsciint.2012.04.003.

[112] A. M. Veitenheimer, J. R. Wagner, Evaluation of Oral Fluid as a Specimen for DUID, Journal of Analytical Toxicology 41 (6) (2017) 517–522. doi:10.1093/jat/bkx036.

[113] H. Furuhaugen, R. E. Jamt, G. Nilsson, V. Vindenes, H. Gjerde, Roadside survey of alcohol and drug use among Norwegian drivers in 2016–2017: A follow-up of the 2008–2009 survey, Traffic Injury Prevention 19 (6) (2018) 555–562. doi:10.1080/15389588.2018.1478087.

[114] M. Davidian, P. D. Haaland, Regression and calibration with nonconstant error variance, Chemometrics and Intelligent Laboratory Systems 9 (3) (1990) 231–248. doi:10.1016/0169-7439(90)80074-G.

[115] H. T. Karnes, G. Shiu, V. P. Shah, Validation of bioanalytical methods, Pharmaceutical Research 8 (4) (1991) 421–426. doi:10.1023/A:1015882607690.

[116] P. Hubert, P. Chiap, J. Crommen, B. Boulanger, E. Chapuzet, N. Mercier, S. Bervoas-Martin, P. Chevalier, D. Grandjean, P. Lagorce, et al., The SFSTP guide on the validation of chromatographic methods for drug bioanalysis: from the Washington Conference to the laboratory, Analytica Chimica Acta 391 (2) (1999) 135–148. doi: 10.1016/S0003-2670(99)00106-3.

[117] Bioanalytical Method Validation – Guidance for Industry, Standard, Food and Drug Administration, Silver Springs, United States (May 2001). URL http://www.fda.gov/downloads/Drugs/Guidances/ucm070107.pdf

[118] F. T. Peters, O. H. Drummer, F. Musshoff, Validation of new methods, Forensic Science International 165 (2-3) (2007) 216–224. doi:10.1016/j.forsciint.2006.05.021.

[119] V. P. Shah, K. K. Midha, J. W. Findlay, H. M. Hill, J. D. Hulse, I. J. McGilveray, G. McKay, K. J. Miller, R. N. Patnaik, M. L. Powell, et al., Bioanalytical method validation - a revisit with a decade of progress, Pharmaceutical Research 17 (12) (2000) 1551–1557. doi:10.1023/A:1007669411738.

[120] F. T. Peters, Method validation using LC-MS, in: A. Polettini (Ed.), Applications of LC-MS in Toxicology, Pharmaceutical Press, London, United Kingdom, 2006, Ch. 4, pp. 71–96.

[121] C. Hartmann, J. Smeyers-Verbeke, D. Massart, R. McDowall, Validation of bioanalytical chromatographic methods, Journal of Pharmaceutical and Biomedical Analysis 17 (2) (1998) 193–218. doi:10.1016/S0731-7085(97)00198-2.

[122] W. Penninckx, C. Hartmann, D. Massart, J. Smeyers-Verbeke, Validation of the calibration procedure in atomic absorption spectrometric methods, Journal of Analytical Atomic Spectrometry 11 (4) (1996) 237–246. doi:10.1039/JA9961100237.

[123] J. Burrows, K. Watson, Linearity of chromatographic systems in drug analysis part I: theory of nonlinearity and quantification of curvature, Bioanalysis 7 (14) (2015) 1731–1743. doi:10.4155/bio.15.103.

[124] E. Pagliano, Z. Mester, J. Meija, Calibration graphs in isotope dilution mass spectrometry, Analytica Chimica Acta 896 (2015) 63–67. doi:10.1016/j.aca.2015.09.020.

[125] C. Moore, S. Rana, C. Coulter, Determination of meperidine, tramadol and oxycodone in human oral fluid using solid phase extraction and gas chromatography–mass spectrometry, Journal of Chromatography B 850 (1-2) (2007) 370–375. doi: 10.1016/j.jchromb.2006.12.008.

[126] M. Cociglio, H. Peyriere, D. Hillaire-Buys, R. Alric, Application of a standardized coextractive cleanup procedure to routine high-performance liquid chromatography assays of teicoplanin and ganciclovir in plasma, Journal of Chromatography B: Biomedical Sciences and Applications 705 (1) (1998) 79–85. doi:10.1016/S0378-4347(97)00499-4.

[127] A. Gupta, B. Jansson, P. Chatelain, R. Massingham, M. Hammarlund-Udenaes, Quantitative determination of cetirizine enantiomers in guinea pig plasma, brain tissue and microdialysis samples using liquid chromatography/tandem mass spectrometry, Rapid Communications in Mass Spectrometry 19 (12) (2005) 1749–1757. doi:10.1002/rcm.1983.

[128] F. T. Peters, H. H. Maurer, Bioanalytical method validation and its implications for forensic and clinical toxicology – A review, Accreditation and Quality Assurance 7 (11) (2002) 441–449. doi:10.1007/s00769-002-0516-5.

[129] E. Rozet, A. Ceccato, C. Hubert, E. Ziemons, R. Oprean, S. Rudaz, B. Boulanger, P. Hubert, Analysis of recent pharmaceutical regulatory documents on analytical method validation, Journal of Chromatography A 1158 (1-2) (2007) 111–125. doi: 10.1016/j.chroma.2007.03.111.

[130] D. Massart, B. Vandeginste, L. Buydens, S. De Jong, P. Lewi, J. Smeyers-Verbeke, Some important hypothesis tests, in: Handbook of Chemometrics and Qualimetrics: Part A, Vol. 20A of Data Handling in Science and Technology, Elsevier, Amsterdam, Netherlands, 1997, Ch. 5, pp. 93–120.

[131] R. D. Cook, S. Weisberg, Diagnostic methods using residuals, in: Residuals and Influence in Regression, Chapman and Hall, New York, United States, 1982, Ch. 2, pp. 10–100.

[132] A. G. González, M. Á. Herrador, A practical guide to analytical method validation, including measurement uncertainty and accuracy profiles, Trends in Analytical Chemistry 26 (3) (2007) 227–238. doi:10.1016/j.trac.2007.01.009.

[133] D. A. Darling, The Kolmogorov-Smirnov, Cramer-von Mises tests, The Annals of Mathematical Statistics 28 (4) (1957) 823–838.

[134] J. Miller, J. C. Miller, Statistics of repeated measurements, in: Statistics and Chemometrics for Analytical Chemistry, 6th Edition, Pearson Education, Harlow, England, 2010, Ch. 3, pp. –37–73.

[135] A. W. van der Vaart, J. A. Wellner, The bootstrap, in: Weak Convergence and Empirical Processes: With Applications to Statistics, Springer, New York, United States, 1996, Ch. 3.6, pp. 345–359.

[136] B. Desharnais, F. Camirand-Lemyre, P. Mireault, C. D. Skinner, Determination of confidence intervals in non-normal data: application of the bootstrap to cocaine concentration in femoral blood, Journal of Analytical Toxicology 39 (2) (2015) 113–117. doi:10.1093/jat/bku127.

[137] J. A. W. Wellner, A. W. van der Vaart, Empirical processes indexed by estimated functions, in: Asymptotics: Particles, Processes and Inverse Problems, Vol. 55 of Lecture Notes - Monograph Series, Institute of Mathematical Statistics, 2007, pp. 234–252. doi:10.1214/074921707000000382.

[138] Y. Zhao, G. Liu, J. X. Shen, A.-F. Aubry, Reasons for calibration standard curve slope variation in LC–MS assays and how to address it, Bioanalysis 6 (11) (2014) 1439–1443. doi:10.4155/bio.14.71.

[139] P. Hubert, J.-J. Nguyen-Huu, B. Boulanger, E. Chapuzet, N. Cohen, P.-A. Compagnon, W. Dewé, M. Feinberg, M. Laurentie, N. Mercier, et al., Harmonization of strategies for the validation of quantitative analytical procedures: A SFSTP proposal– Part III, Journal of Pharmaceutical and Biomedical Analysis 45 (1) (2007) 82–96. doi:10.1016/j.jpba.2007.06.032.

[140] K. Lanckmans, R. Clinckers, A. Van Eeckhaut, S. Sarre, I. Smolders, Y. Michotte, Use of microbore LC–MS/MS for the quantification of oxcarbazepine and its active metabolite in rat brain microdialysis samples, Journal of Chromatography B 831 (1-2) (2006) 205–212. doi:10.1016/j.jchromb.2005.12.003.

[141] C. Apostolou, Y. Dotsikas, C. Kousoulos, Y. L. Loukas, Development and validation of an improved high-throughput method for the determination of anastrozole in human plasma by LC–MS/MS and atmospheric pressure chemical ionization, Journal of Pharmaceutical and Biomedical Analysis 48 (3) (2008) 853–859. doi:10.1016/j.jpba.2008.06.006.

[142] L. B. Nilsson, G. Eklund, Direct quantification in bioanalytical LC–MS/MS using internal calibration via analyte/stable isotope ratio, Journal of Pharmaceutical and Biomedical Analysis 43 (3) (2007) 1094–1099. doi:10.1016/j.jpba.2006.09.030.

[143] V. Pirro, V. Valente, P. Oliveri, A. De Bernardis, A. Salomone, M. Vincenti, Chemometric evaluation of nine alcohol biomarkers in a large population of clinically classified subjects: pre-eminence of ethyl glucuronide concentration in hair for confirmatory classification, Analytical and Bioanalytical Chemistry 401 (7) (2011) 2153. doi:10.1007/s00216-011-5314-7.

[144] V. L. Fulgoni III, D. R. Keast, H. R. Lieberman, Trends in intake and sources of caffeine in the diets of US adults: 2001–2010, The American Journal of Clinical Nutrition 101 (5) (2015) 1081–1087. doi:10.3945/ajcn.113.080077.

[145] H. Andresen-Streichert, A. Müller, A. Glahn, G. Skopp, M. Sterneck, Alcohol biomarkers in clinical and forensic contexts, Deutsches Ärzteblatt International 115 (18) (2018) 309. doi:10.3238/arztebl.2018.0309.

[146] National Health and Nutrition Examination Survey, Data, National Center for Health Statistics, U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Hyattsville, United States (2018). URL http://www.cdc.gov/nchs/nhanes.htm

[147] S. Elliott, C. Smith, D. Cassidy, The post-mortem relationship between beta-hydroxybutyrate (BHB), acetone and ethanol in ketoacidosis, Forensic Science International 198 (1-3) (2010) 53–57. doi:10.1016/j.forsciint.2009.10.019.

[148] E. Osuna, G. Vivero, J. Conejero, J. M. Abenza, P. Martínez, A. Luna, M. D. Pérez-Cárceles, Postmortem vitreous humor _-hydroxybutyrate: its utility for the postmortem interpretation of diabetes mellitus, Forensic Science International 153 (2-3) (2005) 189–195. doi:10.1016/j.forsciint.2004.09.105.

[149] S. Savard, C. Lapointe, M. Lamarche, P. Mireault, Development of a New Method for Simultaneous Quantitative BHB and GHB Analysis by GC-MS, Poster presentation, International Association of Forensic Sciences (IAFS) 2017 Meeting, Toronto, Canada (2017).

[150] Instructions: BSTFA + TMCS N,O-bis(Trimethylsilyl)trifluoroacetamide with Trimethylchlorosilane, Handbook, ThermoFisher Scientific (2017). URL https://fscimage.fishersci.com/images/D00369~.pdf

[151] W. Navidi, Propagation of error, in: Statistics for Engineers and Scientists, Mc Graw Hill Education, New York, United States, 2014, Ch. 3, pp. 164–199.

[152] S. Zörntlein, A. Kopp, J. Becker, T. Kaufmann, J. Röhrich, R. Urban, In vitro production of GHB in blood and serum samples under various storage conditions, Forensic Science International 214 (1-3) (2012) 113–117. doi:10.1016/j.forsciint.2011.07.030.

[153] B. Desharnais, G. Huppé, M. Lamarche, P. Mireault, C. D. Skinner, Cyanide quantification in post-mortem biological matrices by headspace GC–MS, Forensic Science International 222 (1–3) (2012) 346–351. doi:10.1016/j.forsciint.2012.06.017.

[154] O. González, M. E. Blanco, G. Iriarte, L. Bartolomé, M. I. Maguregui, R. M. Alonso, Bioanalytical chromatographic method validation according to current regulations, with a special focus on the non-well defined parameters limit of quantification, robustness and matrix effect, Journal of Chromatography A 1353 (2014) 10–27. doi:10.1016/j.chroma.2014.03.077.

[155] S. M. Wille, W. Coucke, T. De Baere, F. T. Peters, Update of standard practices for new method validation in forensic toxicology, Current Pharmaceutical Design 23 (36) (2017) 5442–5454. doi:10.2174/1381612823666170714154444.

[156] R. Parikh, A. Mathai, S. Parikh, G. C. Sekhar, R. Thomas, Understanding and using sensitivity, specificity and predictive values, Indian Journal of Ophthalmology 56 (1) (2008) 45. doi:10.4103/0301-4738.37595.

[157] D. G. Altman, J. M. Bland, Diagnostic tests. 1: Sensitivity and specificity, British Medical Journal 308 (6943) (1994) 1552. doi:10.1136/bmj.308.6943.1552.

[158] C. Côté, B. Desharnais, M.-A. Morel, J. Laquerre, M.-P. Taillon, G. Daigneault, C. D. Skinner, P. Mireault, High Throughput Protein Precipitation: Screening and Quantification of 106 Drugs and their Metabolites using LC-MS/MS, Oral presentation, 2017 Society of Forensic Toxicologists Meeting (SOFT) and 55th Annual Meeting of the International Association of Forensic Toxicologists (TIAFT), Boca Raton, United States (January 2018).

[159] E. Trullols, I. Ruisanchez, F. X. Rius, Validation of qualitative analytical methods, Trends in Analytical Chemistry 23 (2) (2004) 137–145. doi:10.1016/S0165-9936(04)00201-8.

[160] G. Y. Yi, Statistical Analysis with Measurement Error or Misclassification: Strategy, Method and Application, Springer, New York, United States, 2017.

[161] Cannabis Act, Legislation S.C. 2018, c. 16, Government of Canada, Ottawa, Canada (2018). URL https://laws-lois.justice.gc.ca/eng/acts/C-24.5/

[162] J. Borzelleca, H. Cherrick, The excretion of drugs in saliva. Antibiotics., Journal of Oral Therapeutics and Pharmacology 2 (3) (1965) 180.

[163] M. G. Horning, L. Brown, J. Nowlin, K. Lertratanangkoon, P. Kellaway, T. E. Zion, Use of saliva in therapeutic drug monitoring, Clinical Chemistry 23 (2) (1977) 157–164.

[164] O. H. Drummer, Drug testing in oral fluid, Clinical Biochemist Reviews 27 (3) (2006) 147.

[165] O. Quintela, D. J. Crouch, D. M. Andrenyak, Recovery of drugs of abuse from the Immunalysis Quantisal™ oral fluid collection device, Journal of Analytical Toxicology 30 (8) (2006) 614–616. doi:10.1093/jat/30.8.614.

[166] M. H. Tang, C. Ching, S. Poon, S. S. Chan, W. Ng, M. Lam, C. Wong, R. Pao, A. Lau, T. W. Mak, Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine, Forensic Science International 286 (2018) 113–120. doi:10.1016/j.forsciint.2018.03.004.

[167] M. Gröschl, Saliva: a reliable sample matrix in bioanalytics, Bioanalysis 9 (8) (2017) 655–668. doi:10.4155/bio-2017-0010.

[168] A. Doyon, L. Paradis-Tanguay, F. Crispino, A. Lajeunesse, Les analyses médico-légales de salives: expertise vis-à-vis l’analyse des drogues, Canadian Society of Forensic Science Journal 50 (2) (2017) 90–102. doi:10.1080/00085030.2017.1303254.

[169] C. Cohier, B. Mégarbane, O. Roussel, Illicit drugs in oral fluid: Evaluation of two collection devices, Journal of Analytical Toxicology 41 (1) (2017) 71–76. doi:10.1093/jat/bkw100.

[170] A. J. Krotulski, A. L. Mohr, M. Friscia, B. K. Logan, Field detection of drugs of abuse in oral fluid using the Alere™ DDS® 2 mobile test system with confirmation by liquid chromatography tandem mass spectrometry (LC–MS/MS), Journal of Analytical Toxicology 42 (3) (2017) 170–176. doi:10.1093/jat/bkx105.

[171] S. M. Wille, V. Di Fazio, N. Samyn, La salive dans les investigations toxicologiques: considérations pratiques et analytiques, in: P. Kintz (Ed.), Traité De Toxicologie Médico-judiciaire, Elsevier Masson, Paris, France, 2012, Ch. 8, pp. 219–255.

[172] A. G. Verstraete, Oral fluid testing for driving under the influence of drugs: history, recent progress and remaining challenges, Forensic Science International 150 (2-3) (2005) 143–150. doi:10.1016/j.forsciint.2004.11.023.

[173] Approved Drug Screening Equipment Order, Legislation SOR/2018-179, Government of Canada, Ottawa, Canada (2018). URL https://laws-lois.justice.gc.ca/PDF/SOR-2018-179.pdf

[174] Drug Screening Equipment – Oral Fluid Standards and Evaluation Procedures, Standard, Canadian Society of Forensic Science Drugs and Driving Committee, Ottawa, Canada (2017). URL https://www.csfs.ca/wp-content/uploads/2017/11/Approval-Standards-for-Drug-Screening-Equipment.pdf

[175] Order Amending the Approved Drug Screening Equipment Order, Legislation, Government of Canada, Ottawa, Canada (2019). URL http://www.gazette.gc.ca/rp-pr/p1/2019/2019-04-20/html/reg4-eng.html

[176] E. Viel, E. Blais, P. Mireault, Statistical Overview of Drug Findings in Urine Samples from the DRE Program in the Province of Québec, Canada, Poster presentation, 2013 Society of Forensic Toxicologists Meeting (SOFT), Orlando, United States (2013).

[177] D. Menasco, C. Summit, J. Neifeld, S. Marin, L. Williams, E. Gairloch, Practical Considerations using Quantisal Oral Fluid Collection Devices & SPE Method Development by Polymeric Mixed-Mode Cation Exchange, Poster presentation, Annual Congress in Clinical Mass Spectrometry, Palm Springs, United States (2018). URL http://www.weber.hu/Downloads/SPE/Posters/P179_oral_fluid_evolute_CX.pdf

[178] R. Gudihal, S. Babu CV, N. Tang, S. Palaniswamy, U. S, S. Basingi, Analysis of Polyethylene Glycol (PEG) and a Mono and Di-PEGylated Therapeutic Protein Using HPLC and Q-TOF Mass Spectrometry, Application Note 5991-1509EN, Agilent Technologies, United States (2012). URL https://www.agilent.com/cs/library/applications/5991-1509EN.pdf

[179] N. Fabresse, H. Aouad, A. Knapp, C. Mayer, I. Etting, I. A. Larabi, J.-C. Alvarez, Development and validation of a liquid chromatography-tandem mass spectrometry method for simultaneous detection of 10 illicit drugs in oral fluid collected with FLOQSwabs™ and application to real samples, Drug Testing and Analysis 11 (6) (2019) 824–832. doi:10.1002/dta.2563.

[180] R. Leverence, M. J. Avery, O. Kavetskaia, H. Bi, C. E. Hop, A. I. Gusev, Signal suppression/enhancement in HPLC-ESI-MS/MS from concomitant medications, Biomedical Chromatography 21 (11) (2007) 1143–1150. doi:10.1002/bmc.863.

[181] D. Lee, G. Milman, A. J. Barnes, R. S. Goodwin, J. Hirvonen, M. A. Huestis, Oral fluid cannabinoids in chronic, daily cannabis smokers during sustained, monitored abstinence, Clinical Chemistry 57 (8) (2011) 1127–1136. doi:10.1373/clinchem.2011.164822.

[182] E. Saar, D. Gerostamoulos, O. H. Drummer, J. Beyer, Assessment of the stability of 30 antipsychotic drugs in stored blood specimens, Forensic Science International 215 (1-3) (2012) 152–158. doi:10.1016/j.forsciint.2011.02.022.

[183] D. C. Mata, Stability of 26 sedative hypnotics in six toxicological matrices at different storage conditions, Journal of Analytical Toxicology 40 (8) (2016) 663–668. doi: 10.1093/jat/bkw084.

[184] A. Parkinson, B. W. Ogilvie, D. B. Buckley, F. Kazmi, M. Czerwinski, O. Parkinson, Biotransformation of xenobiotics, in: C. D. Klaassen (Ed.), Casarett & Doull’s Toxicology: The Basic Science of Poisons, 8th Edition, McGraw-Hill Education / Medical, New York, United States, 2013, Ch. 6, pp. 185–366.

[185] F. P. Guengerich, Cytochromes P450, drugs, and diseases, Molecular Interventions 3 (4) (2003) 194. doi:10.1124/mi.3.4.194.

[186] Y. Gasche, Y. Daali, M. Fathi, A. Chiappe, S. Cottini, P. Dayer, J. Desmeules, Codeine intoxication associated with ultrarapid CYP2D6 metabolism, New England Journal of Medicine 351 (27) (2004) 2827–2831. doi:10.1056/NEJMoa041888.

[187] J. George, C. Liddle, M. Murray, K. Byth, G. C. Farrell, Pre-translational regulation of cytochrome P450 genes is responsible for disease-specific changes of individual P450 enzymes among patients with cirrhosis, Biochemical Pharmacology 49 (7) (1995) 873–881. doi:10.1016/0006-2952(94)00515-N.

[188] F. P. Guengerich, C. G. Turvy, Comparison of levels of several human microsomal cytochrome P-450 enzymes and epoxide hydrolase in normal and disease states using immunochemical analysis of surgical liver samples, Journal of Pharmacology and Experimental Therapeutics 256 (3) (1991) 1189–1194.

[189] J. Hansen, J. Palmfeldt, K. W. Pedersen, A. D. Funder, L. Frost, J. B. Hasselstrøm, J. R. Jornil, Postmortem protein stability investigations of the human hepatic drug metabolizing cytochrome P450 enzymes CYP1A2 and CYP3A4 using mass spectrometry, Journal of Proteomics 194 (2019) 125–131. doi:10.1016/j.jprot.2018.11.024.

[190] B. L. Williamson, S. Purkayastha, C. L. Hunter, L. Nuwaysir, J. Hill, L. Easterwood, J. Hill, Quantitative protein determination for CYP induction via LC-MS/MS, Proteomics 11 (1) (2011) 33–41. doi:10.1002/pmic.201000456.

[191] A. Bowdler, T. Chan, The time course of red cell lysis in hypotonic electrolyte solutions, The Journal of Physiology 201 (2) (1969) 437–452. doi:10.1113/jphysiol.1969.sp008765.

[192] L. E. Westerman, P. E. Jensen, Liposomes Composed of Reconstituted Membranes for Induction of Tumor-Specific Immunity, Methods in Enzymology 373 (2003) 118–127. doi:10.1016/S0076-6879(03)73008-0.

[193] W. Konigsberg, Reduction of disulfide bonds in proteins with dithiothreitol, Methods in Enzymology 25 (1972) 185–188. doi:10.1016/S0076-6879(72)25015-7.

[194] S. F. Betz, Disulfide bonds and the stability of globular proteins, Protein Science 2 (10) (1993) 1551–1558. doi:10.1002/pro.5560021002.

[195] B. Herbert, M. Galvani, M. Hamdan, E. Olivieri, J. MacCarthy, S. Pedersen, P. G. Righetti, Reduction and alkylation of proteins in preparation of two-dimensional map analysis: Why, when, and how?, Electrophoresis 22 (10) (2001) 2046–2057. doi: 10.1002/1522-2683(200106)22:10<2046::AID-ELPS2046>3.0.CO;2-C.

[196] Human cytochrome P450 IID6 (CYP2D6) gene, complete cds, Data, National Center for Biotechnology Information (NCBI), Bethesda, United States (1994). URL http://www.ncbi.nlm.nih.gov/nuccore/M33388.1

[197] CYP3A4 - Cytochrome P450 3A4 - Homo sapiens (Human) - CYP3A4 gene & protein, Data, National Center for Biotechnology Information (NCBI), Bethesda, United States. URL https://www.uniprot.org/uniprot/P08684

[198] H.-G. Xie, R. B. Kim, A. J. Wood, C. M. Stein, Molecular basis of ethnic differences in drug disposition and response, Annual Review of Pharmacology and Toxicology 41 (1) (2001) 815–850. doi:10.1146/annurev.pharmtox.41.1.815.

[199] Bradford, L DiAnne, CYP2D6 allele frequency in european caucasians, asians, africans and their descendants, Pharmacogenomics 3 (2) (2002) 229–243. doi:10.1517/14622416.3.2.229.

[200] J. K. Lamba, Y. S. Lin, K. Thummel, A. Daly, P. B. Watkins, S. Strom, J. Zhang, E. G. Schuetz, Common allelic variants of cytochrome P4503A4 and their prevalence in different populations, Pharmacogenetics and Genomics 12 (2) (2002) 121–132.

[201] L. Eriksson, E. Johansson, N. Kettaneh-Wold, C. Wikström, S. Wold, Design of Experiments: Principles and Applications, Umetrics Academy, Umea, Sweden, 2008. 194

[202] P. R. Cook, C. Glenn, A. Armston, Effect of hemolysis on insulin determination by the Beckman Coulter Unicell DXI 800 immunoassay analyzer, Clinical Biochemistry 43 (6) (2010) 621–622. doi:10.1016/j.clinbiochem.2010.01.002.

[203] I. Ojanperä, A. Sajantila, L. Vinogradova, A. Thomas, W. Schänzer, M. Thevis, Postmortem vitreous humour as potential specimen for detection of insulin analogues by LC–MS/MS, Forensic Science International 233 (1-3) (2013) 328–332. doi:10.1016/j.forsciint.2013.10.009.

[204] A. Corthals, A. Koller, D. W. Martin, R. Rieger, E. I. Chen, M. Bernaski, G. Recagno, L. M. Dávalos, Detecting the immune system response of a 500 year-old Inca mummy, PloS one 7 (7) (2012) e41244. doi:10.1371/journal.pone.0041244.

[205] C. Wadsworth, M. Buckley, Proteome degradation in fossils: investigating the longevity of protein survival in ancient bone, Rapid Communications in Mass Spectrometry 28 (6) (2014) 605. doi:10.1002/rcm.6821.

[206] M. Lamare, R. G. Taylor, L. Farout, Y. Briand, M. Briand, Changes in proteasome activity during postmortem aging of bovine muscle, Meat Science 61 (2) (2002) 199–204. doi:10.1016/S0309-1740(01)00187-5.

[207] J. R. Whiteaker, L. Zhao, L. Anderson, A. G. Paulovich, An automated and multiplexed method for high throughput peptide immunoaffinity enrichment and multiple reaction monitoring mass spectrometry-based quantification of protein biomarkers, Molecular & Cellular Proteomics 9 (1) (2010) 184–196. doi:10.1074/mcp.M900254-MCP200.

[208] R. Lametsch, P. Roepstorff, E. Bendixen, Identification of protein degradation during post-mortem storage of pig meat, Journal of Agricultural and Food Chemistry 50 (20) (2002) 5508–5512. doi:10.1021/jf025555n.

[209] M. Oscarson, M. Hidestrand, I. Johansson, M. Ingelman-Sundberg, A combination of mutations in the CYP2D6*17 (CYP2D6Z) allele causes alterations in enzyme function, Molecular Pharmacology 52 (6) (1997) 1034–1040. doi:10.1124/mol.52.6.1034.

[210] R. Baselt, Disposition of Toxic Drugs and Chemicals in Man, 11th Edition, Biomedical Publications, Seal Beach, United States, 2017.

[211] Compendium of Pharmaceuticals and Specialties, Canadian Pharmacists Association, Ottawa, Canada, 2019.

[212] A. C. Moffat, M. D. Osselton, B. Widdop, Clarke’s Analysis of Drugs and Poisons, 4th Edition, Vol. 2, Pharmaceutical Press, London, United Kingdom, 2011.

[213] D. K. Molina, V. J. DiMaio, Normal organ weights in men: Part II—the brain, lungs, liver, spleen, and kidneys, The American Journal of Forensic Medicine and Pathology 33 (4) (2012) 368–372. doi:10.1097/PAF.0b013e31823d29ad.

[214] P. Magalhães, G. Alves, A. LLerena, A. Falcão, Clinical drug-drug interactions: focus on venlafaxine, Drug Metabolism and Personalized Therapy 30 (1) (2015) 3–17. doi: 10.1515/dmdi-2014-0011.

[215] M. Schulz, S. Iwersen-Bergmann, H. Andresen, A. Schmoldt, Therapeutic and toxic blood concentrations of nearly 1,000 drugs and other xenobiotics, Critical Care 16 (4) (2012) R136. doi:10.1186/cc11441.

[216] A. Salomone, E. Gerace, D. Di Corcia, E. Alladio, M. Vincenti, P. Kintz, Hair analysis can provide additional information in doping and forensic cases involving clostebol, Drug Testing and Analysis 11 (1) (2019) 95–101. doi:10.1002/dta.2469.

[217] O. Deltombe, T. Mertens, S. Eloot, A. G. Verstraete, Development and validation of an ultra-high performance liquid chromatography–high resolution mass spectrometry method for the quantification of total and free teicoplanin in human plasma, Clinical Biochemistry 65 (2019) 29–37. doi:10.1016/j.clinbiochem.2018.12.010.

[218] E. Amante, E. Alladio, A. Salomone, M. Vincenti, F. Marini, G. Alleva, S. De Luca, F. Porpiglia, Correlation between chronological and physiological age of males from their multivariate urinary endogenous steroid profile and prostatic carcinoma-induced deviation, Steroids 139 (2018) 10–17. doi:10.1016/j.steroids.2018.09.007.

[219] E. Alladio, G. Biosa, F. Seganti, D. Di Corcia, A. Salomone, M. Vincenti, M. R. Baumgartner, Systematic optimisation of ethyl glucuronide extraction conditions from scalp hair by design of experiments and its potential effect on cut-off values appraisal, Drug Testing and Analysis 10 (9) (2018) 1394–1403. doi:10.1002/dta.2405.

[220] C. Bozzolino, S. Vaglio, E. Amante, E. Alladio, E. Gerace, A. Salomone, M. Vincenti, Individual and cyclic estrogenic profile in women: structure and variability of the data, Steroids (2019) [Advanced article] doi:10.1016/j.steroids.2019.108432.

[221] L. Vaillancourt, B. Desharnais, N. Goudreau, P. Mireault, Interference of fetal hemoglobin in the determination of carboxyhemoglobin by spectrophotometry, Canadian Society of Forensic Science Journal 49 (2) (2016) 69–77. doi:10.1080/00085030.2015.1115692.

[222] American Statistical Association Position on Statistical Statements for Forensic Evidence, Position statement, American Statistical Association, Alexandria, United States (January 2019). URL https://www.amstat.org/asa/files/pdfs/POL-ForensicScience.pdf

[223] M. Bauer, I. Gramlich, S. Polzin, D. Patzelt, Quantification of mRNA degradation as possible indicator of postmortem interval—a pilot study, Legal Medicine 5 (4) (2003) 220–227. doi:10.1016/j.legalmed.2003.08.001.

[224] D. Wessel, U. Flügge, A method for the quantitative recovery of protein in dilute solution in the presence of detergents and lipids, Analytical Biochemistry 138 (1) (1984) 141–143. doi:10.1016/0003-2697(84)90782-6.

[225] S. Sechi, Quantitative Proteomics by Mass Spectrometry, 2nd Edition, Humana Press, Totowa, United States, 2016.

[226] K. Marcus, Quantitative Methods in Proteomics, Humana Press, Totowa, United States, 2012.

[227] C. E. Eyers, S. Gaskell, Quantitative Proteomics, Royal Society of Chemistry, London, United Kingdom, 2014.

[228] R. G. Krishna, F. Wold, Post-translational modifications of proteins, in: K. Imahori, F. Sakiyama (Eds.), Methods in Protein Sequence Analysis, Springer, Boston, United States, 1993, pp. 167–172. doi:10.1007/978-1-4899-1603-7_21.

[229] V. Czitrom, One-factor-at-a-time versus designed experiments, The American Statistician 53 (2) (1999) 126–131. doi:10.1080/00031305.1999.10474445.

[230] B. Achour, J. Barber, A. Rostami-Hodjegan, Expression of hepatic drug-metabolizing cytochrome P450 enzymes and their intercorrelations: a meta-analysis, Drug Metabolism and Disposition 42 (8) (2014) 1349–1356. doi:10.1124/dmd.114.058834.

[231] S. Michaels, M. Z. Wang, The revised human liver cytochrome P450 “Pie”: absolute protein quantification of CYP4F and CYP3A enzymes using targeted quantitative proteomics, Drug Metabolism and Disposition 42 (8) (2014) 1241–1251. doi:10.1124/dmd.114.058040.

[232] A. Cieślak, I. Kelly, J. Trottier, M. Verreault, E. Wunsch, P. Milkiewicz, G. Poirier, A. Droit, O. Barbier, Selective and sensitive quantification of the cytochrome P450 3A4 protein in human liver homogenates through multiple reaction monitoring mass spectrometry, Proteomics 16 (21) (2016) 2827–2837. doi:10.1002/pmic.201500386.

[233] M. Cronin, M. Pho, D. Dutta, J. C. Stephans, S. Shak, M. C. Kiefer, J. M. Esteban, J. B. Baker, Measurement of gene expression in archival paraffin-embedded tissues: development and performance of a 92-gene reverse transcriptase-polymerase chain reaction assay, The American Journal of Pathology 164 (1) (2004) 35–42. doi:10.1016/S0002-9440(10)63093-3.

[234] M. Aguiar, R. Masse, B. F. Gibbs, Regulation of cytochrome P450 by posttranslational modification, Drug Metabolism Reviews 37 (2) (2005) 379–404. doi:10.1081/DMR-46136.

[235] J. Côté, Wilfrid Derome: Expert en homicides, Les éditions du Boréal, Montréal, Canada, 2003.