The simultaneous, quantitative and rapid analysis of plasma concentrations of multiple drugs is important to determine the clinical decision and to expect the prognosis in patients administered in emergency unit with intoxication. Here, we developed the liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based drug screening method for analyzing 12 drugs (acetaminophen, amitriptyline, chlorpromazine, cimetidine, diazepam, doxylamine, ephedrine, imipramine, metoclopramide, propranolol, tramadol, and zolpidem) with frequent events of intoxication throughout the country and evaluated its clinical applicability. The overall sensitivity (low limit of quantitation, 0.1-0.5 μg/mL), specificity, precision and accuracy for the quantification of 12 drugs were reliable and all drugs can be analyzed within 6 min. Among 12 drugs in samples for quality control, the REMEDi HS-based method detected only 6 drugs with low accuracy, while the LC-MS/MS system was able to precisely quantify all drugs. In addition, pilot analysis of patient samples with unknown drug intoxication was superior to the conventional LC-based drug profiling system, and was rapid and cost effective. In conclusion, LC-MS/MS-based drug screening is a good replacement for conventional LC-based REMEDi analyzer and has the better clinical applicability.Keywords Liquid chromatography mass spectrometry, LC-MS/MS, REMEDi analyzer, Drug screeningThe first priority of the treatment of the poisoned patients arrived in emergency department is clinical stabilization 1,2 . Once the poisoned patients is clinically stabilized, it should be estimated the level of exposure to the poison. However, particularly in the case of intentional self-poisoning, it may be difficult to collect the information about poisons in numerous cases. The quantitative determination of plasma concentration of overdosed drug can often provide both prognostic and therapeutic guidance. For example, the plasma concentration of salicylate or acetaminophen in overdosed patient is useful to determine the therapeutic strategy using nomogram 3 . However, if health providers fail to obtain the information about poisoned drugs or chemicals, the appropriate quantitative analysis method for the determination of unknown materials will be great useful. Several tens of toxins or drugs are commonly poisoned in human. The characteristics of poisons are different according to the country, culture, socioeconomic status, or urbanization. For instance, intoxication by organophosphorus insecticides and herbicides are relatively common in rural area, whereas abused opioids or other clinical drugs are common intoxicants in urban region. The liquid chromatography with ultraviolet detection (LC/UV) platform for screening of poisoned drugs in biologic samples was widely used for several decades 4 . However, there are many limitations are present, including sensitivity, time-consuming of sample preparation, chromatographic separation, and lack of quantification. Therefore, the more efficient and precise method to