Implementing an accurate method of standard addition using the EZMSA Excel or R tool.

The method of standard addition (MSA) is a quantification method in which aliquots of an unknown sample are spiked with increasing concentrations of the analyte targeted for quantification. When a regression is performed on the resulting dataset, the unknown concentration is estimated by obtaining the absolute value of the intercept with the concentration axis. As described by the authors in the paper "Achieving a more accurate method of standard addition through mathematical improvements", optimized selection of the spiked concentrations and calibration model (weight and order) yields more accurate MSA quantification results. This is complemented by measurement uncertainty calculation which adds additional confidence to the quantification result. Save for the selection of upspike concentrations, these improvements call for a level of proficiency in mathematics and programming that goes beyond what is considered basic for a forensic or analytical toxicologist. That is a strong impediment to the dissemination of best MSA practices. To remove this barrier, we developed a user-friendly tool: EZMSA. Available as an Excel spreadsheet and an online or local application, this tool carries out all the optimized MSA calculations for the user. The R application even allows the production of a customized report in PDF, DOCX or HTML formats. Validation of both EZMSA platforms was performed by analyzing various datasets testing the full scope of functions and calculations included in the tool. Two full application examples, where EZMSA is used for the quantification of alprazolam and phenazolam in blood, are also presented. The EZMSA tool for simple implementation of accurate MSA calculations is available for download in its Excel and R formats at https://github.com/ToxBrigitte/ezmsa; and as an online application at https://toxbrigitte.shinyapps.io/EZMSA/.