The aim of this presentation is to describe the application of standard addition in forensic toxicology analysis for the rapid reporting of novel psychoactive substances (NPS). Standard addition is a quantitative analytical approach where the drug to be analyzed is fortified directly into aliquots of sample being tested, using the sample as its own matrix-matched control. The procedure can thus be used for quantitative determinations in multiple tissues and fluids. To achieve a quantitative result via standard addition, four replicate samples were aliquoted, three of which were fortified with the analyte of interest. All four samples were then extracted using liquid-liquid extraction with borax buffer (0.1 M, pH 10.4), and N-butyl chloride/ethyl acetate (70:30 v:v) as the extraction solvent. An analytical method for the compounds of interest was developed using a liquid chromatograph tandem mass spectrometer (Waters Xevo TQ-S micro). A method verification was performed on all standard addition methods with parameters adopted from the AAFS Standards Board (ASB) recommendations prior to testing authentic specimens. The method verification assessed linearity over the target range, limit of detection, recovery, and interference from matrix, analyte, internal standard, and commonly encountered drugs, as well as analysis of fortified control samples. Quantitative values were calculated by plotting the resulting analyte-internal standard peak area ratio (PAR) against the up-spike concentration, and a linear trendline between all data points was calculated. The concentration in the sample is determined by the x-intercept of the trendline with a correlation (R2) greater than 0.98. We have used the above approach to develop and validate methods for a variety of compounds in our laboratory to accelerate the process of reporting identifications and concentrations of new and emerging drugs. This allows us to support early dissemination of information and analytical data about new NPS compounds to laboratories, clinicians, and other stakeholders. This presentation describes its use for testing for N-pyrrolidino etonitazene (opioid), dimethylpentylone (stimulant), and 2-methyl AP-237/AP-238 (opioids). The linear dynamic range of N-pyrrolidino etonitazene and 2-methyl AP-237/AP-238 was evaluated from 0.1–100 ng/mL, and for dimethylpentylone it was evaluated from 1–500 ng/mL. No compounds demonstrated interferences for matrix, internal standard, analyte, or commonly encountered interferences. Recovery was also evaluated, and all analytes had a recovery of > 88%. Fortified control samples resulted in concentrations within ±20% of the target value. For dimethylpentylone, dilution studies were also performed; samples were diluted with water prior to the fortification with drug standards and demonstrated accurate quantitative values (±20%). Due to the tests being carried out within the matrix that is being tested, a larger sample volume is needed. Also, since standard addition involves testing each sample in replicates of four including the spikes, instrument capacity is increased, and costs are higher. The approach is best suited to less frequently encountered substances. Standard addition also requires some assumptions about the likely concentration of the substance that will be quantitated to determine what up-spike values are necessary. This can be done by evaluating the response of the analyte during our liquid chromatography quadrupole time of flight mass spectrometry screening analysis, and consideration of data of closely related drugs. With the everchanging and rapid turnover of the NPS market, standard addition may be the suitable choice for laboratories to report out a quantitative value without going through a costly comprehensive method validation. If a compound does become more prevalent such that standard addition is not appropriate for a long-term testing approach, standard addition can be a solution until validation of the complete method is completed. This would allow laboratories to provide toxicology data on NPS in a timelier manner to assist in making case interpretations.